共查询到20条相似文献,搜索用时 15 毫秒
1.
M. N. Mordi S. M. Mansor V. Navaratnam & W. H. Wernsdorfer 《British journal of clinical pharmacology》1997,43(4):363-365
Aims To determine the pharmacokinetics of artemether (ARM) and its principal active metabolite, dihydroartemisinin (DHA) in healthy volunteers.
Methods Six healthy male Malaysian subjects were given a single oral dose of 200 mg artemether. Blood samples were collected to 72 h. Plasma concentrations of the two compounds were measured simultaneously by reversed-phase h.p.l.c. with electrochemical detection in the reductive mode.
Results Mean (± s.d.) maximum concentrations of ARM, 310±153 μg l−1 , were reached 1.88±0.21 h after drug intake. The mean elimination half-life was 2.00±0.59 h, and the mean AUC 671±271 μg l−1 h. The mean C max of DHA, 273±64 μg l−1 , was observed at 1.92±0.13 h. The mean AUC of DHA was 753±233 μg h l−1 . ARM and DHA were stable at ≤−20° C for at least 4 months in plasma samples.
Conclusions The relatively short half-life of ARM may be one of the factors responsible for the poor radical cure rate of falciparum malaria with regimens employing daily dosing. In view of the rapid loss of DHA in plasma samples held at room temperature (26° C) it is recommended to store them at a temperature of ≤−20° C as early as possible after sample collection. 相似文献
Methods Six healthy male Malaysian subjects were given a single oral dose of 200 mg artemether. Blood samples were collected to 72 h. Plasma concentrations of the two compounds were measured simultaneously by reversed-phase h.p.l.c. with electrochemical detection in the reductive mode.
Results Mean (± s.d.) maximum concentrations of ARM, 310±153 μg l
Conclusions The relatively short half-life of ARM may be one of the factors responsible for the poor radical cure rate of falciparum malaria with regimens employing daily dosing. In view of the rapid loss of DHA in plasma samples held at room temperature (26° C) it is recommended to store them at a temperature of ≤−20° C as early as possible after sample collection. 相似文献
2.
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
3.
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
4.
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
![点击此处可从《British journal of clinical pharmacology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
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
5.
Effect of food on the bioavailability of triclabendazole in patients with fascioliasis 总被引:2,自引:0,他引:2
下载免费PDF全文
![点击此处可从《British journal of clinical pharmacology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Lecaillon Godbillon Campestrini Naquira Miranda Pacheco Mull & Poltera 《British journal of clinical pharmacology》1998,45(6):601-604
Aims Preliminary results indicate higher absorption of triclabendazole (TCBZ) administered postprandially. Therefore, the influence of food on the pharmacokinetics of TCBZ and its active sulphoxide (TCBZ-SO) and sulphone (TCBZ-SO2) metabolites was investigated.
Methods Two single doses (10 mg kg−1 ) of TCBZ were administered to 20 patients with fascioliasis. Ten patients were first given the drug after a high energy breakfast and then, 48 h later, after an overnight fast. The other 10 patients first received the drug in fasting state and then, 48 h later, after breakfast. A low energy breakfast was served 2 h after drug administration for fasting state.
Results Compared with the fasting state, an increased AUC and Cmax after food intake (significant, P <0.0001) was shown from the values of TCBZ, TCBZ-SO and TCBZ-SO2. The mean AUC for TCBZ (fasting: 1.55, fed: 5.72 μmol l−1 h), TCBZ-SO (fasting: 177, fed: 386 μmol l−1 h) and TCBZ-SO2 (fasting: 13.9, fed: 30.5 μmol l−1 h) indicated a large availability increase with food and the strong systemic predominance of the active sulphoxide metabolite over the unchanged drug. (All patients were cured at the end of the trial except one who required a second course of two postprandial doses of triclabendazole (10 mg kg−1 each). Tolerability to the treatment among the patients was good.
Conclusions The administration of triclabendazole with food is recommended for improved systemic availability in patients with fascioliasis or paragonimiasis. 相似文献
Methods Two single doses (10 mg kg
Results Compared with the fasting state, an increased AUC and C
Conclusions The administration of triclabendazole with food is recommended for improved systemic availability in patients with fascioliasis or paragonimiasis. 相似文献
6.
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
7.
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
![点击此处可从《British journal of clinical pharmacology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
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
8.
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
9.
Jun-Sheng Wang Wei Wang Hong-Guang Xie Song-Lin Huang & Hong-Hao Zhou 《British journal of clinical pharmacology》1997,44(2):195-198
Aims In vitro data indicate that imipramine (IMI), a widely used tricyclic antidepressant drug, is N -demethylated by several isoforms of cytochrome P450, which include CYP3A4. The aim of this study was to investigate the role of CYP3A in the in vivo N -demethylation of IMI.
Methods Healthy subjects were given troleandomycin (TAO), a selective inhibitor of CYP3A, 250 mg daily for 2 days before a single oral dose of 100 mg IMI was administered.
Results Pretreatment with TAO significantly increased the AUC of IMI by 59% (1971±938 vs 3134±2000 μg l−1 h, 95% confidence interval for difference between means: 218 to 2108 μg l−1 h, P <0.05) and decreased its oral clearance by 30% (60.9±27.4 vs 42.5±22.7 l h−1 , 95% confidence internal for difference between means: 7.2 to 31.7 l h−1 , P <0.05).
Conclusions We conclude that CYP3A may play an important role in the in vivo N -demethylation of IMI. 相似文献
Methods Healthy subjects were given troleandomycin (TAO), a selective inhibitor of CYP3A, 250 mg daily for 2 days before a single oral dose of 100 mg IMI was administered.
Results Pretreatment with TAO significantly increased the AUC of IMI by 59% (1971±938 vs 3134±2000 μg l
Conclusions We conclude that CYP3A may play an important role in the in vivo N -demethylation of IMI. 相似文献
10.
1 The metabolism of diazepam to its primary metabolites 3-hydroxydiazepam (3HDZ) and nordiazepam (NDZ) was evaluated in human liver microsomes. The 3HDZ pathway was the major route of metabolism representing 90% of total metabolism with a V max /K m ratio of 0.50–7.26 μl min−1 mg −1 protein.
2 Inhibition of the two metabolic pathways of diazepam by omeprazole was investigated. The NDZ pathway was not affected by omeprazole whilst a Ki of 201±89 μm was obtained for the 3HDZ pathway ( K m /K i ratio of 3.0±0.9).
3 Inhibitory effects of omeprazole sulphone on the 3HDZ and NDZ pathways were also investigated. Omeprazole sulphone inhibited both pathways with similar Ki s of 121±45 and 188±73 μm respectively ( K m /K i ratios of 5.2±2.3 and 3.3±1.5 respectively).
4 These in vitro data provide direct evidence for cytochrome P450 inhibition as the mechanism for the well documented diazepam-omeprazole clinical interaction and indicate that omeprazole sulphone, as well as the parent drug, contribute to the inhibition effect. 相似文献
2 Inhibition of the two metabolic pathways of diazepam by omeprazole was investigated. The NDZ pathway was not affected by omeprazole whilst a K
3 Inhibitory effects of omeprazole sulphone on the 3HDZ and NDZ pathways were also investigated. Omeprazole sulphone inhibited both pathways with similar K
4 These in vitro data provide direct evidence for cytochrome P450 inhibition as the mechanism for the well documented diazepam-omeprazole clinical interaction and indicate that omeprazole sulphone, as well as the parent drug, contribute to the inhibition effect. 相似文献
11.
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
![点击此处可从《British journal of clinical pharmacology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
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
12.
Pharmacokinetics of recombinant human interleukin-2 in advanced renal cell carcinoma patients following subcutaneous application
下载免费PDF全文
![点击此处可从《British journal of clinical pharmacology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
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
13.
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
14.
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
15.
Clonidine and or adrenaline decrease lignocaine plasma peak concentration after epidural injection 总被引:1,自引:0,他引:1
JEAN XAVIER MAZOIT DAN BENHAMOU YVES VEILLETTE & KAMRAN SAMII 《British journal of clinical pharmacology》1996,42(2):242-245
Clonidine is an α2 -adrenoceptor agonist increasingly used in combination with lignocaine for spinal or epidural anaesthesia because of a prolonged analgesic effect. Like adrenaline, it may decrease lignocaine peak concentration ( C max ), thus leading to decreased toxicity. However, the effects of clonidine on resorption of lignocaine into the systemic circulation from the epidural space remain to be established. We studied the pharmacokinetics of lignocaine after epidural injection of lignocaine with or without clonidine, adrenaline and both drugs. Total body clearance and apparent volume of distribution were similar in the four groups, but the maximum observed concentration ( C max ) was markedly increased in the plain solution group as compared with the other groups: (plain lignocaine: 7.15±2.04 μg ml−1 , lignocaine+adrenaline: 3.11±136 μg ml−1 , lignocaine+clonidine: 4.48±1.26 μg ml−1 , lignocaine+adrenaline+clonidine: 4.06±1.42 μg ml−1 [mean±s.d.]). Our results show that, clonidine decreases lignocaine C max to the same extent as adrenaline. 相似文献
16.
C. J. EAGLES M. J. KENDALL & S. MAXWELL 《British journal of clinical pharmacology》1996,41(5):381-387
1 We have examined the interaction between aerobic exercise and lipid-lowering drugs in a crossover study of 16 healthy normolipidaemic volunteers who each received 21 days' treatment with bezafibrate (400 mg), fluvastatin (40 mg), and placebo, in random order.
2 Fluvastatin treatment reduced pre-exercise total cholesterol (TC) by 23% ( P <0.0001), low-density lipoprotein cholesterol (LDL-C) by 33% ( P <0.0001), and plasma triglycerides by 11%, compared with pre-treatment values. Bezafibrate reduced TC by 11% ( P <0.01); LDL-C by 9%; and plasma triglycerides by 40% ( P <0.01), compared with pre-treatment values.
3 During exercise, in comparison with placebo, and fluvastatin treatment, respectively, bezafibrate significantly reduced mean fat oxidation: 31% vs 39%, P =0.035, 31% vs 39%, P =0.002, plasma free fatty acid (FFA) availability, e.g. after 90 min of exercise: ( t 90) 520 vs 662 μmol l−1 , P =0.054, 520 vs 725 μmol l−1 , P =0.016, and plasma levels of glycerol ( t 90): 59 vs 74 μmol l−1 , P =0.037, 59 vs 73 μmol l−1 , P =0.016. Fluvastatin had no impact on fat metabolism in comparison with placebo.
4 Reduced plasma FFA concentration and lower fat oxidation during prolonged exercise on bezafibrate treatment may be due to an inhibition of hepatic acetyl coenzyme A carboxylase, resulting in reduced FFA release from adipose tissue.
5 The possibility that impaired fat metabolism on fibrates could induce premature fatigue during exercise of moderate duration and intensity should be examined in hyperlipidaemic patients. 相似文献
2 Fluvastatin treatment reduced pre-exercise total cholesterol (TC) by 23% ( P <0.0001), low-density lipoprotein cholesterol (LDL-C) by 33% ( P <0.0001), and plasma triglycerides by 11%, compared with pre-treatment values. Bezafibrate reduced TC by 11% ( P <0.01); LDL-C by 9%; and plasma triglycerides by 40% ( P <0.01), compared with pre-treatment values.
3 During exercise, in comparison with placebo, and fluvastatin treatment, respectively, bezafibrate significantly reduced mean fat oxidation: 31% vs 39%, P =0.035, 31% vs 39%, P =0.002, plasma free fatty acid (FFA) availability, e.g. after 90 min of exercise: ( t 90) 520 vs 662 μmol l
4 Reduced plasma FFA concentration and lower fat oxidation during prolonged exercise on bezafibrate treatment may be due to an inhibition of hepatic acetyl coenzyme A carboxylase, resulting in reduced FFA release from adipose tissue.
5 The possibility that impaired fat metabolism on fibrates could induce premature fatigue during exercise of moderate duration and intensity should be examined in hyperlipidaemic patients. 相似文献
17.
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
18.
D. J. Birkett J. O. Miners L. Valente K. J. Lillywhite & R. O. Day 《British journal of clinical pharmacology》1997,43(2):197-200
Aims In the present study we have investigated the use of caffeine, administered in the form of instant coffee, as a prodrug for 1MX to validate the use of the 1MU:1MX ratio following caffeine administration as a pharmacodynamic measure of oxypurinol effect on xanthine oxidase.
Methods Five healthy volunteers took caffeine 75 mg 8 hourly administered as instant coffee over a 7 day period. They were given allopurinol 600 mg on day 4. Urine was collected in 8 h aliquots from day 1–day 7. The ratio of 1-methyluric acid (1MU) to 1-methylxanthuric (1MX) was determined.
Results The relationship between the plasma oxypurinol (the active metabolite of allopurinol) concentration at the midpoint of each caffeine dosage interval and the decrement in the urinary 1MX to 1MU ratio fitted well by a sigmoid Emax model. Mean (±s.d.) values of the oxypurinol E C 50 (3.9±1.4 mg l− 1 ), E C 90 (8.7±1.8 mg l− 1 ) and the exponent, n (3.0±1.2) were similar to those obtained previously following either the direct administration of 1MX or the use of theophylline as a prodrug for 1MX.
Conclusions These data indicate that the use of caffeine as a source of 1MX could provide a simple and ethically acceptable method for monitoring oxypurinol effect in patients taking allopurinol for the treatment of gout. 相似文献
Methods Five healthy volunteers took caffeine 75 mg 8 hourly administered as instant coffee over a 7 day period. They were given allopurinol 600 mg on day 4. Urine was collected in 8 h aliquots from day 1–day 7. The ratio of 1-methyluric acid (1MU) to 1-methylxanthuric (1MX) was determined.
Results The relationship between the plasma oxypurinol (the active metabolite of allopurinol) concentration at the midpoint of each caffeine dosage interval and the decrement in the urinary 1MX to 1MU ratio fitted well by a sigmoid E
Conclusions These data indicate that the use of caffeine as a source of 1MX could provide a simple and ethically acceptable method for monitoring oxypurinol effect in patients taking allopurinol for the treatment of gout. 相似文献
19.
Pharmacodynamics of benserazide assessed by its effects on endogenous and exogenous levodopa pharmacokinetics* 总被引:2,自引:1,他引:1
Jasper Dingemanse Cornelis H. Kleinbloesem Gerhard Zürcher Nolan D. Wood & Charles Crevoisier 《British journal of clinical pharmacology》1997,44(1):41-48
Aims The objectives of the study were to investigate the pharmacodynamics of the peripheral decarboxylase inhibitor benserazide during multiple-dose regimens.
Methods Two groups of eight healthy male subjects were consecutively treated for periods of 14 days with benserazide 5, 25, 100 mg three times daily and 12.5, 50, 200 mg three times daily, respectively. Plasma levels of levodopa, 3- O -methyldopa (3-OMD) and 3,4-dihydroxyphenylacetic acid (DOPAC) were determined before benserazide treatment and during all benserazide dosing regimens, as existing endogenously and after administration of 250 mg levodopa.
Results Endogenous concentrations of levodopa and 3-OMD increased dose-dependently (from 8 up to 52 μg l−1 and from 0.02 up to 0.50 mg l−1 , respectively, at doses of 200 mg) with ascending doses of benserazide whereas DOPAC levels remained unchanged. There were no indications of a plateau in the effects of benserazide on the plasma levels of the analytes. The area under the concentration-time curve (AUC) of exogenously administered levodopa increased from 1.2 in the control group to 5.9 mg l−1 h at benserazide doses of 100–200 mg three times daily. Benserazide caused a dose-dependent increase in the AUC of 3-OMD from 7.4 to 106 mg l−1 h at doses of 200 mg. Formation of DOPAC was dose-dependently suppressed, with benserazide 5 mg three times daily already halving its AUC.
Conclusions The benserazide-dose response data obtained suggest that even at very high doses extracerebral decarboxylase is not yet completely inhibited. 相似文献
Methods Two groups of eight healthy male subjects were consecutively treated for periods of 14 days with benserazide 5, 25, 100 mg three times daily and 12.5, 50, 200 mg three times daily, respectively. Plasma levels of levodopa, 3- O -methyldopa (3-OMD) and 3,4-dihydroxyphenylacetic acid (DOPAC) were determined before benserazide treatment and during all benserazide dosing regimens, as existing endogenously and after administration of 250 mg levodopa.
Results Endogenous concentrations of levodopa and 3-OMD increased dose-dependently (from 8 up to 52 μg l
Conclusions The benserazide-dose response data obtained suggest that even at very high doses extracerebral decarboxylase is not yet completely inhibited. 相似文献
20.
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