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1.
No effect of short-term omeprazole intake on acenocoumarol pharmacokinetics and pharmacodynamics 总被引:1,自引:0,他引:1
J. N. J. M. de Hoon H. H. W. Thijssen A. J. M. M. Beysens & L. M. A. B. Van Bortel 《British journal of clinical pharmacology》1997,44(4):399-401
Aims To investigate the effect of omeprazole on the pharmacokinetics of R- and S-acenocoumarol and on their combined anticoagulant activity.
Methods Eight healthy male subjects completed a double-blind, randomized, placebo-controlled, two-way cross-over study. Subjects were given either omeprazole 40 mg or placebo once daily for 3 days. On day 2 of each study period, a single 10 mg oral dose of racemic acenocoumarol was administered and venous blood samples were collected for pharmacokinetic and pharmacodynamic assessments. A wash-out period of 2 weeks separated the two study periods.
Results The pharmacokinetics of R- and S-acenocoumarol (AUC 3016±221 and 233±14 ng ml−1 h, respectively) did not change after omeprazole (AUC 2929±256 and 220±18 ng ml−1 h, respectively). Anticoagulant activity (INRmax 1.7±0.1) was unaffected by co-administration of omeprazole (INRmax 1.7±0.1).
Conclusions The short-term intake of omeprazole does not affect acenocoumarol pharmacokinetics or pharmacodynamics. These data differ from the results of previous studies on the effect of omeprazole on warfarin, suggesting a different in vivo interaction profile of omeprazole on acenocoumarol than on warfarin. Drug interaction studies with oral anticoagulants should not be restricted to the use of warfarin. 相似文献
Methods Eight healthy male subjects completed a double-blind, randomized, placebo-controlled, two-way cross-over study. Subjects were given either omeprazole 40 mg or placebo once daily for 3 days. On day 2 of each study period, a single 10 mg oral dose of racemic acenocoumarol was administered and venous blood samples were collected for pharmacokinetic and pharmacodynamic assessments. A wash-out period of 2 weeks separated the two study periods.
Results The pharmacokinetics of R- and S-acenocoumarol (AUC 3016±221 and 233±14 ng ml
Conclusions The short-term intake of omeprazole does not affect acenocoumarol pharmacokinetics or pharmacodynamics. These data differ from the results of previous studies on the effect of omeprazole on warfarin, suggesting a different in vivo interaction profile of omeprazole on acenocoumarol than on warfarin. Drug interaction studies with oral anticoagulants should not be restricted to the use of warfarin. 相似文献
2.
The interaction between propranolol and the novel antimigraine agent zolmitriptan (311C90) 总被引:1,自引:1,他引:0
Richard W. Peck Emma J. Seaber Ruth Dixon Catherine G. Gillotin† Barry C. Weatherley Gary Layton & John Posner‡ 《British journal of clinical pharmacology》1997,44(6):595-599
Aims Zolmitriptan (Zomig, formerly known as 311C90), a selective 5HT1B/1D agonist is under development as an acute oral treatment for migraine. Despite the use of prophylactic medication, such as propranolol, breakthrough attacks often occur in patients. Consequently we investigated the effects of propranolol on the pharmacokinetics of, and cardiovascular responses to, zolmitriptan.
Methods A double-blind, randomized, crossover study of the effects of pre-treatment with propranolol 160 mg daily for 7 days or placebo on the pharmacokinetics and effects on blood pressure of a single 10 mg dose of zolmitriptan in 12 healthy volunteers.
Results Propranolol increased mean zolmitriptan Cmax and AUC by 56% and 37% respectively; mean t 1/2 was prolonged from 3.1 to 4.0 h. Mean C max and AUC of the pharmacologically active N -desmethyl metabolite were reduced by 24% and 11% respectively and the metabolite:parent AUC ratio (AUCm /AUCp ) fell from 0.46 to 0.26. Mean C max and AUC for the inactive indole acetic acid metabolite were both reduced by 13% and AUCm /AUCp from 1.04 to 0.59. A small pressor effect of short duration was observed following zolmitriptan with mean peak rises of 13 and 11 mmHg in systolic and diastolic pressures respectively; propranolol had no effect on the pressor response.
Conclusions The results suggest that propranolol inhibits biotransformation of zolmitriptan but with no change in the small pressor response to zolmitriptan. It is therefore unlikely that the pharmacokinetic changes will lead to clinically important changes in pharmacological effects and dosage adjustment of zolmitriptan is not required in patients taking propranolol for migraine prophylaxis. 相似文献
Methods A double-blind, randomized, crossover study of the effects of pre-treatment with propranolol 160 mg daily for 7 days or placebo on the pharmacokinetics and effects on blood pressure of a single 10 mg dose of zolmitriptan in 12 healthy volunteers.
Results Propranolol increased mean zolmitriptan C
Conclusions The results suggest that propranolol inhibits biotransformation of zolmitriptan but with no change in the small pressor response to zolmitriptan. It is therefore unlikely that the pharmacokinetic changes will lead to clinically important changes in pharmacological effects and dosage adjustment of zolmitriptan is not required in patients taking propranolol for migraine prophylaxis. 相似文献
3.
L. W. Fu L. Y. Yang W. P. Chen & C. Y. Lin 《British journal of clinical pharmacology》1997,44(2):125-127
Aims Neoral is a new microemulsion form of cyclosporin. Pharmacokinetic reports in children are scarce. Therefore, we performed a pharmacokinetic study between Cyclosporin A (CsA) capsules and Neoral in paediatric patients with lupus nephritis.
Methods A single 5 mg kg−1 dose orally of either CsA capsules or Neoral was given to 10 paediatric patients (serum creatinine<1.5 mg dl−1 ). CsA whole blood levels were measured for 24 h post-dose by h.p.l.c.
Results Neoral had a higher Cmax and AUC( C max : 943±176 ng ml−1 ; AUC: 4612±785 ng ml−1 h) than those of the CsA capsules ( C max : 697±187 ng ml−1 ; AUC: 3483±873 ng ml−1 h; P <0.05). There was no difference in t max and t 1/2,z between the two groups.
Conclusions CsA Neoral had improved absorption and bioavailability, which is similar to what is reported in adults. However, interpatient variability still existed. Careful drug monitoring and dose adjustment should be performed during treatment to avoid nephrotoxicity, especially in lupus nephritis. 相似文献
Methods A single 5 mg kg
Results Neoral had a higher C
Conclusions CsA Neoral had improved absorption and bioavailability, which is similar to what is reported in adults. However, interpatient variability still existed. Careful drug monitoring and dose adjustment should be performed during treatment to avoid nephrotoxicity, especially in lupus nephritis. 相似文献
4.
The effect of nateglinide on the pharmacokinetics and pharmacodynamics of acenocoumarol 总被引:1,自引:0,他引:1
Sunkara G Bigler H Wang Y Smith H Prasad P McLeod J Ligueros-Saylan M 《Current medical research and opinion》2004,20(1):41-48
OBJECTIVE: The potential for a drug interaction was investigated between nateglinide, an oral antidiabetic agent, and acenocoumarol, an oral anticoagulant, as these drugs are primarily metabolized via CYP2C9. METHODS: A two-period, randomized, double-blind, two-way crossover study design was employed to evaluate the effect of nateglinide on the pharmacokinetics and pharmacodynamics of acenocoumarol in 11 healthy male or female subjects. All subjects received either nateglinide 120 mg t.i.d. or placebo for 5 days in a crossover fashion and a single 10-mg dose of acenocoumarol on day 3. Plasma concentrations of R- and S-acenocoumarol and the anticoagulation parameters [prothrombin time (PT) and international normalized ratio of PT (PTINR)] were determined for 72 h following acenocoumarol administration. The pharmacokinetic and pharmacodynamic parameters of acenocoumarol were determined by noncompartmental analysis. RESULTS: The mean (coefficient of variation (CV%)) area under the concentration-time curve (AUC(0-t)) of R-acenocoumarol in the presence and absence of nateglinide was 4217 (23%) and 3831 (24%) ng.h/ml, respectively. The corresponding values for S-acenocoumarol were 397 (20%) and 382 (23%), respectively. The mean (CV%) C(max) of R-acenocoumarol in the presence and absence of nateglinide was 304 (16%) and 316 (16%), respectively and the corresponding values for S-acenocoumarol were 142 (36%) and 141 (34%), respectively. The 90% confidence intervals indicated that exposure parameters, AUC(0-t) and C(max), of both R- and S-acenocoumarol were within the acceptable limits of 0.8-1.25. The mean (CV%) of area under the concentration-time curve of PT (AUC(PT)) following acenocoumarol administration in the presence and absence of nateglinide was 1170 (10%) and 1136 (8%), respectively. The corresponding AUC(INR) values were 104 (13%) and 99 (10%), respectively. Nateglinide co-administration has no influence on the PT or PTINR of acenocoumarol (p > 0.05). CONCLUSION: Co-administration of nateglinide does not influence either the pharmacokinetics or the anticoagulant activity of R- and S-acenocoumarol in healthy subjects. This suggests that no dosage adjustments will be required when nateglinide and acenocoumarol are coadministered in clinical practice. 相似文献
5.
David M. Tenero David E. Martin Ann K. Miller Bernard Ilson Steven C. Boike Névine Zariffa & Diane K. Jorkasky 《British journal of clinical pharmacology》1998,46(3):267-270
Aims To compare the pharmacokinetics of eprosartan between young (18–45 years) and elderly (65 years) men and between young men and young, premenopausal women (18–45 years).
Methods Twenty-four subjects (eight subjects/group) received a single 200 mg eprosartan oral dose followed by serial blood sampling over 24 h.
Results Eprosartan was safe and well tolerated. There were no apparent differences in the pharmacokinetics of eprosartan between young females and young males or in the plasma protein binding of eprosartan (≈98%) for the three groups. On average, AUC (0,∞) and Cmax values were ≈2-fold higher in elderly men than young men [AUC (0,∞) 95% CI: 1.22, 4.34; C max 95% CI: 0.98, 4.00]. Similarly, unbound AUC (0,∞) and C max values were, on average, ≈2-fold higher in elderly men than young men [unbound AUC (0,∞) 95% CI: 1.29, 4.44; unbound C max 95% CI: 1.02, 4.12]. t max was delayed in the elderly men compared with young men, with a median difference of 2.5 h (95% CI: 1.00, 3.01 h).
Conclusions No gender differences were observed in the pharmacokinetics of eprosartan. There were ≈ two fold higher AUC and Cmax values for eprosartan observed in elderly men as compared with young men, most likely due to increased bioavailability of eprosartan in the elderly. Based on the excellent safety profile in the elderly in Phase III clinical trials (doses up to 1200 mg eprosartan) eprosartan can be safely administered to elderly hypertensive patients without an initial dose adjustment. Subsequently, the dose of eprosartan, as for other antihypertensive agents, may be individualized based on tolerability/response. 相似文献
Methods Twenty-four subjects (eight subjects/group) received a single 200 mg eprosartan oral dose followed by serial blood sampling over 24 h.
Results Eprosartan was safe and well tolerated. There were no apparent differences in the pharmacokinetics of eprosartan between young females and young males or in the plasma protein binding of eprosartan (≈98%) for the three groups. On average, AUC (0,∞) and C
Conclusions No gender differences were observed in the pharmacokinetics of eprosartan. There were ≈ two fold higher AUC and C
6.
Lack of effect of eprosartan on the single dose pharmacokinetics of orally administered digoxin in healthy male volunteers 总被引:1,自引:1,他引:0
D. E. Martin D. Tompson S. C. Boike D. Tenero B. Ilson D. Citerone & D. K. Jorkasky 《British journal of clinical pharmacology》1997,43(6):661-664
Aims To study the effect of eprosartan, a nonbiphenyl tetrazole angiotensin II receptor antagonist, on digoxin pharmacokinetics in a randomized, open-label, two period, period balanced crossover study in 12 healthy men.
Methods Each subject received a single 0.6 mg oral dose of digoxin (Lanoxicaps® 0.2 mg/capsule, Glaxo Wellcome) alone or following 4 days of dosing with eprosartan 200 mg orally every 12 h. Each study period was separated by a 14 day washout interval. Serial blood samples were obtained for up to 96 h after each digoxin dose for determination of digoxin pharmacokinetics. The effect of eprosartan on digoxin pharmacokinetics was assessed through an equivalence-type approach using AUC(0, t ') as the primary endpoint.
Results For AUC(0, t '), the ratio of digoxin+eprosartan:digoxin alone was 0.99 with a 90% confidence interval (CI) of [ 0.90, 1.09]. For Cmax , the ratio was 1.00 with a 90% CI of [0.86, 1.17]. t max was similar for both regimens. Both regimens were safe and well tolerated.
Conclusions Based on AUC and Cmax data, it can be concluded that eprosartan has no effect on the pharmacokinetics of a single oral dose of digoxin. 相似文献
Methods Each subject received a single 0.6 mg oral dose of digoxin (Lanoxicaps
Results For AUC(0, t '), the ratio of digoxin+eprosartan:digoxin alone was 0.99 with a 90% confidence interval (CI) of [ 0.90, 1.09]. For C
Conclusions Based on AUC and C
7.
H. Fuder S. Stiegler N. Wetzelsberger G. Wieckhorst R. Lange & P. W. Lücker 《British journal of clinical pharmacology》1997,44(6):527-530
Aims Concomitant administration of magnesium hydroxide may affect the rate or extent of absorption of non-steroidal anti-inflammatory drugs. In order to find out whether or not buffering modifies the pharmacokinetics of ketoprofen, plasma concentration-time courses resulting from oral administration of unbuffered formulations were compared with those of buffered formulations.
Methods Two groups of 12 healthy and young male subjects were included in two randomized cross-over studies and received single oral doses of ketoprofen 12.5 or 25 mg, respectively, given as tablets which were either unbuffered or buffered with magnesium hydroxide/citrate. Ketoprofen enantiomers in plasma were determined by h.p.l.c. up to 24 h post-dose.
Results Maximum plasma concentrations ( Cmax ) of both the (R)- and (S)-enantiomer, observed after administration of the buffered formulations (12.5 and 25 mg), were higher compared with the unbuffered tablets by about 50–80%. The area under concentration-time data (AUC) was unaffected, and, hence, C max /AUC was increased by buffering. Time to C max ( t max ) and mean residence time (MRT) tended to be or was shortened by buffering.
Conclusions It is concluded that buffering of two ketoprofen formulations with magnesium hydroxide/citrate enhanced the concentration maximum by increasing the rate of absorption and leaving AUC unaffected. 相似文献
Methods Two groups of 12 healthy and young male subjects were included in two randomized cross-over studies and received single oral doses of ketoprofen 12.5 or 25 mg, respectively, given as tablets which were either unbuffered or buffered with magnesium hydroxide/citrate. Ketoprofen enantiomers in plasma were determined by h.p.l.c. up to 24 h post-dose.
Results Maximum plasma concentrations ( C
Conclusions It is concluded that buffering of two ketoprofen formulations with magnesium hydroxide/citrate enhanced the concentration maximum by increasing the rate of absorption and leaving AUC unaffected. 相似文献
8.
The pharmacokinetics of ziprasidone in healthy volunteers treated with cimetidine or antacid 总被引:4,自引:2,他引:2 下载免费PDF全文
K. D. Wilner R. A. Hansen C. J. Folger & P. Geoffroy 《British journal of clinical pharmacology》2000,49(S1):57-60
Aims To evaluate the effects of cimetidine and Maalox® (aluminium hydroxide 1.35 g and magnesium hydroxide 1.2 g) on the pharmacokinetics of ziprasidone.
Methods Eleven healthy young subjects aged 18–45 years were given single oral doses of ziprasidone 40 mg on three occasions at least 7 days apart. On one occasion ziprasidone was administered alone, on another occasion ziprasidone was co‐administered with oral cimetidine 800 mg and on a third occasion ziprasidone was co‐administered with oral Maalox® .
Results The administration of cimetidine increased the ziprasidone AUC(0,∞) by 6% but there were no statistically significant differences in Cmax , t max or λz between the ziprasidone+cimetidine group and the ziprasidone group. The administration of Maalox® did not produce any statistically significant differences in AUC(0,∞), C max , t max or λz between the ziprasidone+Maalox® group and the ziprasidone group.
Conclusions The pharmacokinetics of ziprasidone are not affected by concurrent administration of cimetidine or Maalox® . This suggests that other nonspecific inhibitors of cytochrome P450 and antacids are unlikely to alter the pharmacokinetics of ziprasidone. 相似文献
Methods Eleven healthy young subjects aged 18–45 years were given single oral doses of ziprasidone 40 mg on three occasions at least 7 days apart. On one occasion ziprasidone was administered alone, on another occasion ziprasidone was co‐administered with oral cimetidine 800 mg and on a third occasion ziprasidone was co‐administered with oral Maalox
Results The administration of cimetidine increased the ziprasidone AUC(0,∞) by 6% but there were no statistically significant differences in C
Conclusions The pharmacokinetics of ziprasidone are not affected by concurrent administration of cimetidine or Maalox
9.
A limited sampling method for the estimation of AUC and Cmax of carbamazepine and carbamazepine epoxide following a single and multiple dose of a sustained-release product 下载免费PDF全文
Aims The objectives of this study are to develop a model to predict area under the curve (AUC) and maximum plasma concentration ( C max ) of carbamazepine (CBZ) and its active metabolite carbamazepine epoxide (CBZE) following single and multiple dose of CBZ using one or two samples in volunteers.
Methods Limited sampling models (LSM) were developed for CBZ and CBZE following 200–800 mg single oral dose and 400–800 mg twice daily dose for 14 days of a sustained-release product (CBZ-SR) to estimate AUC and Cmax . The LSM was developed from a training data set of 15 subjects using one blood sample taken at 48 h following a single dose. The model was validated on 60 subjects who received different doses of CBZ. Following multiple dosing, the LSM was developed from a training data set of 10 subjects using the steady state C min (plasma concentration obtained 5 min before the last CBZ-SR dose).
Results The model provided good estimates of AUC and Cmax for CBZ and CBZE. The bias and the precision of the predicted AUC and C max for CBZ and CBZE were less than 10% and 15%, respectively. Similar results were obtained when CBZ was given as multiple dose.
Conclusions The method described here may be used to estimate AUC and Cmax for CBZ and CBZE without detailed pharmacokinetic studies following single or multiple dose of CBZ. 相似文献
Methods Limited sampling models (LSM) were developed for CBZ and CBZE following 200–800 mg single oral dose and 400–800 mg twice daily dose for 14 days of a sustained-release product (CBZ-SR) to estimate AUC and C
Results The model provided good estimates of AUC and C
Conclusions The method described here may be used to estimate AUC and C
10.
Effect of food on the pharmacokinetics of ropinirole in parkinsonian patients 总被引:1,自引:0,他引:1 下载免费PDF全文
C. Brefel C. Thalamas S. Rayet A. Lopez-Gil K. Fitzpatrick S. Bullman D. R. Citerone A. C. Taylor J. L. Montastruc & O. Rascol 《British journal of clinical pharmacology》1998,45(4):412-415
Aims Ropinirole is a specific non-ergoline dopamine D2 -receptor agonist with antiparkinsonian properties.The pharmacokinetic parameters of ropinirole taken in the fasted condition were compared with those when it was co-administered with food.
Methods This was an open, randomized, two sessions cross over study in 12 patients with Parkinson's disease, comparing the steady-state pharmacokinetic profiles of ropinirole on two different study days: 'fasted' and 'fed'.
Results The mean Cmax was lower in the 'fed' regimen than in the 'fasted' one (−25%, P =0.002). The median t max was observed 2.6 h later in the 'fed' regimen than in the 'fasted' regimen ( P <0.05). There was a slight but significant decrease in AUC(0,8 h) in the 'fed' regimen ( P =0.03).
Conclusions Food decreases the rate of absorption of ropinirole, but has little effect on the extent of absorption. 相似文献
Methods This was an open, randomized, two sessions cross over study in 12 patients with Parkinson's disease, comparing the steady-state pharmacokinetic profiles of ropinirole on two different study days: 'fasted' and 'fed'.
Results The mean C
Conclusions Food decreases the rate of absorption of ropinirole, but has little effect on the extent of absorption. 相似文献
11.
Young-Joo Lee Suk-Jae Chung & Chang-Koo Shim 《British journal of clinical pharmacology》1997,44(4):343-345
Aims The objective of this study was to determine the extent of period effect on the pharmacokinetics of cyclosporin A (CsA) during consecutive dosing.
Methods Sandimmune Neoral® and Neoplanta® capsules were administered to twenty-four healthy Korean male subjects at a single CsA dose of 175 mg in a 2×2 crossover investigation with a 2-week wash-out phase. Concentrations of CsA in blood were measured by a r.i.a. method for a period of 48 h.
Results The two formulations were found bioequivalent, but analysis of variance (ANOVA) indicated that there is a significant ( P <0.01) period effect in AUC(0,last) (area under the blood concentration-time curve above the assay limit) and Cmax (maximum blood concentration) between the administrations. A 6 and 9% decrease in the AUC(0,last) and C max , respectively was seen at the second administration.
Conclusions This period effect on the pharmacokinetics of CsA may be relevant for the patients who need consecutive administration of the drug. 相似文献
Methods Sandimmune Neoral
Results The two formulations were found bioequivalent, but analysis of variance (ANOVA) indicated that there is a significant ( P <0.01) period effect in AUC(0,last) (area under the blood concentration-time curve above the assay limit) and C
Conclusions This period effect on the pharmacokinetics of CsA may be relevant for the patients who need consecutive administration of the drug. 相似文献
12.
Effect of ritonavir on the pharmacokinetics of ethinyl oestradiol in healthy female volunteers 总被引:5,自引:1,他引:4 下载免费PDF全文
Daniele Ouellet Ann Hsu Jiang Qian Charles S. Locke Carolyn J. Eason John H. Cavanaugh John M. Leonard & G. Richard Granneman 《British journal of clinical pharmacology》1998,46(2):111-116
Aims To assess the effects of the protease inhibitor ritonavir on the pharmacokinetics of ethinyl oestradiol in healthy female volunteers.
Methods This was an open-label, single centre study in 23 subjects who received two single doses of oral contraceptive containing 50 μg ethinyl oestradiol on Day 1 (alone) and on Day 29 during concomitant ritonavir. Each subject received 16 days of every 12 h doses of ritonavir from Day 15 through Day 30. Blood samples were collected for serum ethinyl oestradiol concentrations for 48 h after each dose and for plasma ritonavir on Day 29 at 0 and 4 h postdose.
Results Statistically significant decreases in ethinyl oestradiol mean Cmax (−32%) and mean AUC (−41%), and a statistically significant increase in the mean terminal elimination rate constant (+31%) were observed during concomitant ritonavir. The harmonic mean terminal half-life decreased from 17 h to 13 h during concomitant ritonavir. No statistically significant change was noted in t max . The ratios of means (95% confidence intervals) for C max and AUC were 0.682 (0.612–0.758) and 0.595 (0.506–0.694), respectively. The changes in ethinyl oestradiol pharmacokinetics were consistent with an increase in clearance from enzymatic induction of glucuronidation and/or cytochrome P450 hydroxylation. Mean steady-state ritonavir concentrations of 6.5 and 13.4 μg ml−1 were observed at 0 and 4 h postdose, respectively.
Conclusions Considering the extent of the decrease in ethinyl oestradiol concentrations, the use of alternate contraceptive measures should be considered when ritonavir is being administered. 相似文献
Methods This was an open-label, single centre study in 23 subjects who received two single doses of oral contraceptive containing 50 μg ethinyl oestradiol on Day 1 (alone) and on Day 29 during concomitant ritonavir. Each subject received 16 days of every 12 h doses of ritonavir from Day 15 through Day 30. Blood samples were collected for serum ethinyl oestradiol concentrations for 48 h after each dose and for plasma ritonavir on Day 29 at 0 and 4 h postdose.
Results Statistically significant decreases in ethinyl oestradiol mean C
Conclusions Considering the extent of the decrease in ethinyl oestradiol concentrations, the use of alternate contraceptive measures should be considered when ritonavir is being administered. 相似文献
13.
R. W. Peck R. Wootton R. Wiggs G. Layton & J. Posner 《British journal of clinical pharmacology》1998,46(1):83-86
Aims To investigate the nasal absorption of hydroxocobalamin in 10 healthy elderly adults.
Methods In a cross-over study, blood samples were collected before administration of the drug and after 10, 20, 30, 40, 60, 120, 180 and 240 min. The plasma cobalamin concentration was determined by competitive radioisotope binding technique.
Results The maximal plasma cobalamin concentration ( Cmax ) after nasal administration of 750 μg hydroxocobalamin was 1900±900 pmol l−1 (mean±s.d.). The maximal plasma cobalamin concentration was reached in 35±13 min ( t max ). The C max after nasal administration of 1500 μg hydroxocobalamin was 3500±2500 pmol l−1 with a t max of 28±16 min. Both the AUC(0,240 min) and AUC(0,00) increased significantly with an increase of the dose from 750 μg to 1500 μg ( P =0.037 and P =0.028, respectively). The nasal spray was well tolerated. No signs of irritation or local sensitivity were noted.
Conclusions The nasal absorption of hydroxocobalamin in healthy elderly adults is rapid, high and well tolerated. 相似文献
Methods In a cross-over study, blood samples were collected before administration of the drug and after 10, 20, 30, 40, 60, 120, 180 and 240 min. The plasma cobalamin concentration was determined by competitive radioisotope binding technique.
Results The maximal plasma cobalamin concentration ( C
Conclusions The nasal absorption of hydroxocobalamin in healthy elderly adults is rapid, high and well tolerated. 相似文献
14.
Dion R. Brocks James Upward Maria Davy Kate Howland Christopher Compton Charles McHugh & Michael J. Dennis 《British journal of clinical pharmacology》1997,44(3):289-291
Aims To study the magnitude of differences in the pharmacokinetics of pranlukast, after morning and evening administration.
Methods Pranlukast (300 mg) was administered to 12 healthy male volunteers on two separate occasions, either in the morning or evening. Both doses were given 30 min after a standard high fat content meal. Blood samples were collected up to 18 h postdose. Plasma was assayed by high performance liquid chromatography. Standard pharmacokinetic and statistical analyses were performed.
Results Statistically significant ( P <0.05) increases were noted in AUC(o, t ) (56%) and tmax (2.5 h) after evening administration. C max was 14% higher after evening dosing (95% C.I. 0.71–1.84).
Conclusions Pranlukast bioavailability is apparently increased after evening dosing as compared with morning administration. Higher night-time and early morning plasma concentrations may confer additional therapeutic benefit at a time when asthmatics are at greatest risk of developing bronchospasm. 相似文献
Methods Pranlukast (300 mg) was administered to 12 healthy male volunteers on two separate occasions, either in the morning or evening. Both doses were given 30 min after a standard high fat content meal. Blood samples were collected up to 18 h postdose. Plasma was assayed by high performance liquid chromatography. Standard pharmacokinetic and statistical analyses were performed.
Results Statistically significant ( P <0.05) increases were noted in AUC(o, t ) (56%) and t
Conclusions Pranlukast bioavailability is apparently increased after evening dosing as compared with morning administration. Higher night-time and early morning plasma concentrations may confer additional therapeutic benefit at a time when asthmatics are at greatest risk of developing bronchospasm. 相似文献
15.
Effects of food and antacid on the pharmacokinetics of single doses of mycophenolate mofetil in rheumatoid arthritis patients 总被引:3,自引:2,他引:1
R. BULLINGHAM J. SHAH R. GOLDBLUM & M. SCHIFF 《British journal of clinical pharmacology》1996,41(6):513-516
1 Mycophenolate mofetil (MMF) is a prodrug of mycophenolic acid (MPA) and is being developed for the prevention of rejection following solid organ transplantation. This crossover study investigated the effect of food and antacid (Maalox® TC) on the plasma pharmacokinetics of MPA and its inactive glucuronide metabolite MPAG after giving single 2 g MMF doses orally to rheumatoid arthritis patients.
2 With food, the AUC of MPA in plasma was equivalent to that following an overnight fast. MPA tmax was slightly delayed and C max was lowered about 25%, consistent with delay in gastric emptying in the fed state. MPAG C max and AUC were higher in the fed relative to the fasting state, suggesting more complex processes involving changes in glucuronidation may also be occurring with food.
3 With antacid, AUC of MPA was lowered about 15% compared with fasting and Cmax was decreased 37%. Plasma MPAG parameters were similarly reduced. These parallel changes in MPA and MPAG are consistent with reduced absorption.
4 The changes in MPA with both food and antacid are small in comparison with the interpatient variability and are not likely to have clinically major effects; the changes in MPAG are of mechanistic interest. 相似文献
2 With food, the AUC of MPA in plasma was equivalent to that following an overnight fast. MPA t
3 With antacid, AUC of MPA was lowered about 15% compared with fasting and C
4 The changes in MPA with both food and antacid are small in comparison with the interpatient variability and are not likely to have clinically major effects; the changes in MPAG are of mechanistic interest. 相似文献
16.
F. VAUZELLE-KERVROËDAN E. REY G. PONS Ph. d'ATHIS C. CHIRON O. DULAC C. DUMAS & G. OLIVE 《British journal of clinical pharmacology》1996,42(6):779-781
The antiepileptic drug vigabatrin (VGB) is a selective irreversible inhibitor of GABA-transaminase. It is administered as a racemic R(−), S(+) mixture, but the pharmacological activity of vigabatrin resides in the S(+) enantiomer and the R(−) enantiomer is inactive. The pharmacokinetic parameters of the two enantiomers have been studied after administration of a single oral 125 mg dose of the racemate to six neonates. The mean values of C max and AUC of the S(+) enantiomer were significantly lower ( C max : 14.0±4.3 mg l−1 ; AUC: 143±44 mg l−1 h) than those of the R(−) enantiomer ( C max : 34.1±9.5 mg l−1 ; AUC: 231±88 mg l−1 h), whereas no significant difference in the time to reach C max (S(+): 2.1±1.1 h; R(−): 2.2±1 h) was observed between the two enantiomers. During chronic administration (125 mg twice daily over 4 days), there was no evidence of accumulation of either enantiomer. 相似文献
17.
Nimish N. Vachharajani Wen Chyi Shyu Robert A. Smith & Douglas S. Greene 《British journal of clinical pharmacology》1998,46(6):611-613
Aims Single dose pharmacokinetics and safety of irbesartan, an angiotensin II receptor antagonist, were evaluated in healthy young and elderly male and female subjects.
Methods Irbesartan was administered as two 25 mg capsules after a 10 h fast to 12 young men, 12 young women, 12 elderly men and 12 elderly women. Serial blood and urine sample were collected up to 96 h after the dose. Plasma and urine samples were analysed for irbesartan by h.p.l.c./fluorescence methods.
Results No statistically significant gender effects were observed in peak plasma concentration ( Cmax ), area under the curve (AUC), and terminal elimination half-life ( t 1/2 ) of irbesartan. The geometric mean AUC and C max increased by about 43% and 49%, respectively, in the elderly subjects. Also the time to peak was significantly shorter in the elderly subjects compared with that observed in the young subjects. Renal clearance of irbesartan was significantly reduced in the elderly females but this reduction is not likely to be of any clinical relevance since less than 3% of the administered dose of irbesartan is excreted unchanged in the urine.
Conclusions Although there was an effect of age on the pharmacokinetics of irbesartan, based on the safety and efficacy profile, no adjustment in irbesartan dosage is necessary with respect to age or gender. 相似文献
Methods Irbesartan was administered as two 25 mg capsules after a 10 h fast to 12 young men, 12 young women, 12 elderly men and 12 elderly women. Serial blood and urine sample were collected up to 96 h after the dose. Plasma and urine samples were analysed for irbesartan by h.p.l.c./fluorescence methods.
Results No statistically significant gender effects were observed in peak plasma concentration ( C
Conclusions Although there was an effect of age on the pharmacokinetics of irbesartan, based on the safety and efficacy profile, no adjustment in irbesartan dosage is necessary with respect to age or gender. 相似文献
18.
Y. BÖTTIGER P. DOSTERT M. STROLIN BENEDETTI M. BANI F. FIORENTINI M. CASATI I. POGGESTI C. ALM G. ALVAN & L. BERTILSSON 《British journal of clinical pharmacology》1996,42(6):707-711
1 Nicergoline, an ergot derivative previously used as a vasodilator, has gained a new indication in treating the symptoms of senile dementia.
2 Nicergoline is rapidly hydrolysed to an alcohol derivative, 1-methyl-10-α-methoxy-9,10-dihydrolysergol (MMDL), which is further N -demethylated to form 10-α-methoxy-9,10-dihydrolysergol (MDL). A few individuals display aberrant metabolism of this drug, as shown by their diminished capacity to form the MDL metabolite. The aim of this study was to determine whether defective nicergoline metabolism is associated with the debrisoquine and/or the S-mephenytoin hydroxylation polymorphisms.
3 After a single, oral 30 mg dose of nicergoline, the plasma concentrations of its two metabolites were studied in 15 subjects, divided into three groups with respect to their debrisoquine and S-mephenytoin hydroxylation phenotypes.
4 The pharmacokinetic parameters of MMDL and MDL were similar in the ten subjects who were extensive metabolisers of debrisoquine (five of whom were poor metabolisers of S-mephenytoin) (mean MMDL Cmax 59 nmol l−1 and AUC (0, t h) 144 nmol l−1 h, mean MDL C max 183 nmol l−1 and AUC 2627 nmol l−1 h) but were markedly different from the five subjects who were poor metabolisers of debrisoquine (mean MMDL C max 356 nmol l−1 and AUC 10512 nmol l−1 h, MDL concentrations below limit of quantitation).
5 We conclude that the formation of MDL from MMDL in the metabolism of nicergoline is catalysed to a major extent by CYP2D6 and that the observed interindividual variation in the metabolic pattern of the drug is related to the debrisoquine hydroxylation polymorphism. 相似文献
2 Nicergoline is rapidly hydrolysed to an alcohol derivative, 1-methyl-10-α-methoxy-9,10-dihydrolysergol (MMDL), which is further N -demethylated to form 10-α-methoxy-9,10-dihydrolysergol (MDL). A few individuals display aberrant metabolism of this drug, as shown by their diminished capacity to form the MDL metabolite. The aim of this study was to determine whether defective nicergoline metabolism is associated with the debrisoquine and/or the S-mephenytoin hydroxylation polymorphisms.
3 After a single, oral 30 mg dose of nicergoline, the plasma concentrations of its two metabolites were studied in 15 subjects, divided into three groups with respect to their debrisoquine and S-mephenytoin hydroxylation phenotypes.
4 The pharmacokinetic parameters of MMDL and MDL were similar in the ten subjects who were extensive metabolisers of debrisoquine (five of whom were poor metabolisers of S-mephenytoin) (mean MMDL C
5 We conclude that the formation of MDL from MMDL in the metabolism of nicergoline is catalysed to a major extent by CYP2D6 and that the observed interindividual variation in the metabolic pattern of the drug is related to the debrisoquine hydroxylation polymorphism. 相似文献
19.
Absorption kinetics of oral sotalol combined with cisapride and sublingual sotalol in healthy subjects 下载免费PDF全文
Deneer Lie-A-Huen Kingma Proost Kelder & Brouwers 《British journal of clinical pharmacology》1998,45(5):485-490
Aims To study the absorption kinetics of sotalol following administration of different formulations. A formulation which results in fast absorption might be useful in the episodic treatment of paroxysmal supraventricular tachycardia (SVT), atrial fibrillation (Afib) or atrial flutter (Afl).
Methods In an open randomized crossover study seven healthy male volunteers were given an intravenous infusion of 20 mg sotalol, for assessing the absolute bioavailability, an oral solution containing 80 mg sotalol, an oral solution containing both 80 mg sotalol and 20 mg cisapride and an 80 mg sotalol tablet, which was taken sublingually.
Results The addition of cisapride decreased the time at which maximum serum concentrations were reached ( tmax ) from 2.79 (1.85–4.34) h to 1.16 (0.68–2.30) h ( P =0.009) [95% CI: -2.59, −0.55] and increased the absorption rate constant ( k a ) from 0.49 (0.31–0.69) h−1 to 1.26 (0.52–5.61) h−1 ( P =0.017). The absolute bioavailability of sotalol was reduced by cisapride from 1.00±0.15 to 0.70±0.26 ( P =0.006), while maximum serum concentrations of both oral solutions were not significantly different. Compared with the sublingually administered tablet with a median t max of 2.12 (0.89–3.28) h, the sotalol/cisapride oral solution gave a smaller t max (p=0.009) [95% CI: −1.64, −0.36]. The k a of the sotalol/cisapride solution was significanty ( P =0.010) larger than the k a of 0.56 (0.33–0.75) h−1 found after sublingual administration of the tablet.
Conclusions The sotalol/cisapride oral solution might be suitable for the episodic treatment of SVT, Afib or Afl. 相似文献
Methods In an open randomized crossover study seven healthy male volunteers were given an intravenous infusion of 20 mg sotalol, for assessing the absolute bioavailability, an oral solution containing 80 mg sotalol, an oral solution containing both 80 mg sotalol and 20 mg cisapride and an 80 mg sotalol tablet, which was taken sublingually.
Results The addition of cisapride decreased the time at which maximum serum concentrations were reached ( t
Conclusions The sotalol/cisapride oral solution might be suitable for the episodic treatment of SVT, Afib or Afl. 相似文献
20.
Pharmacokinetics of recombinant human interleukin-2 in advanced renal cell carcinoma patients following subcutaneous application 下载免费PDF全文
G. I. Kirchner A. Franzke J. Buer W. Beil M. Probst-Kepper F. Wittke K. Övermann S. Lassmann R. Hoffmann H. Kirchner A. Ganser & J. Atzpodien 《British journal of clinical pharmacology》1998,46(1):5-10
Aims The aim of the study was to investigate the pharmacokinetics of recombinant human interleukin-2 (rhIL-2) in patients with metastatic renal cell carcinoma following different subcutaneous (s.c.) administration regimens.
Methods RhIL-2 was administered subcutaneously to 10 patients according to two different dosing regimens: group A received 20×106 IU m−2 once daily and group B 10×106 IU m−2 twice daily (every 12 h). Additionally, in all patients the influence of soluble interleukin-2 receptor (sIL-2R) on the pharmacokinetics of rhIL-2 was investigated.
Results The mean area under the serum concentration-time curve to 24 h (AUC(0,24 h)) was 627 IU ml−1 h in treatment group A and 1130 IU ml−1 h ( P =0.029) in treatment group B. In both study groups C max and AUC(0,12 h) were not significantly different. Seventy-two hours after the beginning of s.c. rhIL-2 therapy the sIL-2R increased significantly ( P =0.016), and sIL-2R levels over 1200 pmol l−1 seemed to reduce the AUC.
Conclusions In patients with metastatic renal cell cancer administration of 20×106 IU m−2 of rhIL-2 s.c. in two daily doses (10×106 IU m−2 every 12 h) provides better bioavailability and is preferable to the single dose administration. 相似文献
Methods RhIL-2 was administered subcutaneously to 10 patients according to two different dosing regimens: group A received 20×10
Results The mean area under the serum concentration-time curve to 24 h (AUC(0,24 h)) was 627 IU ml
Conclusions In patients with metastatic renal cell cancer administration of 20×10