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1.
E. C. Oparaoji S. Siram U. Elemihe H. M. Mezghebe T. Cho M. Bashiri K. Piedrahita R. S. Pipalla 《Journal of clinical pharmacy and therapeutics》1998,23(3):191-197
Objective: To compare aminoglycoside pharmaco?kinetics in African-Americans with normal renal function with published adult population values. Design: An Institutional Review Board approved concurrent study. Setting: The study was conducted at Howard University Hospital, Washington DC. Subjects: All subjects had serum creatinine levels of 1·5 mg/dl or less and were receiving aminoglycoside for suspected or documented Gram-negative infection, had no obvious underlying disease condition that could influence aminoglycoside pharmaco?kinetics and were aged 18 years or older. Main outcome measures: Volume of distribution (Vd), half-life ( t1/2), elimination rate constant (Ke) and total body clearance ( Cl) were calculated using a one-compartment, open, linear pharmacokinetic model. Using an unpaired Student's t-test, the pharmaco?kinetic values of our patients were compared with general population values. Interventions: Patients receiving aminoglysides were identified by the pharmacist through the hospital's standard antibiotic order sheet. Twenty-five patients were enrolled after they met the inclusion criteria. Pharmacists made recommendations for dose change as part of standard of care when inappropriate doses were ordered. In collaboration with medical and nursing staff, the amount and time of dose administration, and steady-state peak and trough serum drug levels were stringently measured, documented on a data collection form and used to calculate pharmacokinetic values for our patients. The form was also used to document demographic information. Results: The following values were obtained: Vd 0·27±0·15 litres/kg, t1/2 1·93±1·38 h, Ke 0·31±0·134/h (gentamicin), Ke 0·22±0·10/h (tobramycin), Cl 103·95±62·98 ml/kg/h (gentamicin) and Cl 118·96±84·83 ml/kg/h (tobramycin). These values are not significantly different from general population values. Following a mean tobramycin or gentamicin dose of 1·32±0·32 mg/kg ideal body weight (IBW)/dose or 1·11±0·33 mg/kg actual body weight (ABW)/dose every 8 h, patients achieved a mean peak and trough serum drug levels of 6·6±3·86 mg/litre and 1·03±0·68 mg/litre, respectively. Wide interpatient pharmacokinetic variability was also observed. Conclusions: We conclude that aminoglycoside pharmacokinetics in African-Americans seem to be consistent with the published general population values. Thus, initiating aminoglycoside regimens using population dosing guidelines appears to be appropriate. However, due to the observed wide interpatient pharmacokinetic variability, in?dividualized dosing is required with very close monitoring, to avoid or minimize toxicity. 相似文献
2.
Therapeutic drug monitoring of tobramycin: once-daily versus twice-daily dosage schedules 总被引:3,自引:0,他引:3
A. Sánchez-Alcaraz A. Vargas M. B. Quintana A. Rocher J. M. Querol J. L. Poveda & M. Hermenegildo 《Journal of clinical pharmacy and therapeutics》1998,23(5):367-373
Objective: To evaluate the effect of dosage regimen (once-daily vs. twice-daily) of tobramicyn on steady-state serum concentrations and toxicity. Materials and methods: Patients undergoing treatment with iv tobramycin (4 mg/kg/day) were randomised to two groups. Group OD ( n=22) received a once-daily dose of tobramycin and group TD (n=21) received the same dose divided into two doses daily. Tobramycin serum concentrations (peak and trough) were measured by enzyme multiplied immunoassay. The renal and auditorory functions of the patients were monitored before, during and immediately after treatment. Results: The two groups were comparable with respect to sex, age, body weight and renal function. No statistically significant differences were found in mean daily dose, duration of treatment, or cumulative dose. Trough concentrations were < 2 μg/ml in the two groups (100%). Peak concentrations were > 6 μg/ml in 100% of the OD group and in 67% of the TD group ( P< 0·01). Mean peak concentrations were markedly different: 11·00±2·89 μg/ml in OD vs. 6·53±1·45 μg/ml in TD ( P< 0·01). The pharmacokinetics parameters were: Ke, (0·15±0·03/h in OD vs. 0·24±0·06/h in TD), t1/2, (4·95±1·41 h in OD vs. 3·07±0·71 h in TD), Vd (0·35±0·11 l/kg in OD vs. 0·33±0·09 l/kg in TD), Cl (0·86±0·29 ml/min/kg in OD vs. 1·28±0·33 ml/min/kg in TD). Increased serum creatinine was observed in 73% of patients in OD versus 57% of patients in TD, without evidence of nephrotoxicity. In TD group, three patients developed decreased auditory function, of which one presented with an auditory loss of –30 dB, whereas in the OD group only one patient presented decreased auditory function. Conclusion: This small study suggests that a once-daily dosing regimen of tobramycin is at least as effective as and is no more and possibly less toxic than the twice-daily regimen. Using a single-dose therapy, peak concentration determination is not necessary, only trough samples should be monitored to ensure levels below 2 μg/ml. 相似文献
3.
Expanded gentamicin volume of distribution in critically ill adult patients receiving total parenteral nutrition 总被引:2,自引:0,他引:2
C. L. Ronchera-Oms PharmD ‡ C. Tormo MD † J. P. Ordovas PharmD † J. Abad PharmD † N. V. Jimenez PharmD § 《Journal of clinical pharmacy and therapeutics》1995,20(5):253-258
Aminoglycoside antibiotics distribute into the extracellular fluid compartment and are eliminated by the kidney via glomerular filtration. Malnutrition and total parenteral nutrition influence the fluid and electrolyte status of the patient, and cause organ changes. The purpose of this clinical study was to characterize the kinetic behaviour of gentamicin in the parenterally fed critically ill adult patient. Eighty–six critically ill adult patients treated with gentamicin for severe Gram–negative infections were enrolled in the study (mean ± SD): age, 60±14 years; weight, 69 4±10 2 kg; height, 163±10 cm; 22 females and 64 males. Four study groups were defined (2 times 2): total parenteral nutrition vs. fluid therapy, and acute renal failure vs. normal renal function. The drug was administered by intermittent intravenous infusion. Blood samples were drawn at steadystate, 5 min before the next dose (‘trough’) and 30 min after the termination of the infusion (‘peak’). Gentamicin serum concentration was determined by fluorescence polarization immunoassay. Gentamicin pharmacokinetic parameters were estimated by non–linear regression analysis, assuming a one–compartment model and first–order elimination from the central compartment. Treatment of malnutrition with total parenteral nutrition increased gentamicin volume of distribution (P < 0 001), but did not affect total body clearance (P= 0 75). This change tended to produce lower peak concentrations (<4 μg/ml, P= 0 07), thus potentially compromising therapeutic effectiveness. There was no significant influence on trough concentrations (P= 0 56). Patients receiving fluid therapy had a volume of distribution of 0 34±0 08 litre/kg, while those fed by the intravenous route showed larger values (0 43±0 12 litre/kg), irrespective of their renal function. This may be explained by the extracellular water expansion caused by stress, malnutrition, and parenteral refeeding. Gentamicin dosage regimens in critically ill adult patients on total parenteral nutrition should be formulated on the basis of larger volumes of distribution and to attain therapeutic serum concentrations higher doses may be required. 相似文献
4.
Abdel-Hady E El Hamamsy M Hedaya M Awad H 《Journal of clinical pharmacy and therapeutics》2011,36(1):45-52
What is known and objective: Neonatal sepsis is one of the most common reasons for admission to neonatal units in developing countries. Aminoglycosides widely used in its treatment are usually administered two or three times a day. Less frequent doing may be more convenient and as effective. We aim to compare the efficacy and safety (nephrotoxicity) of once daily vs. twice daily dosing of amikacin in neonates with suspected or proven sepsis and report on the drug’s pharmacokinetics in these subjects. Methods: Thirty neonates of gestational age ≥36 weeks and body weight ≥2500 g with suspected or proven sepsis were randomized to receive amikacin either at a dose of 15 mg/kg once per day; group I (n = 15), or a dose of 7·5 mg/kg twice per day, group II (n = 15). All neonates received classical treatment of sepsis including antibiotics, hemodynamic support, inotropic support based on blood pressure levels and size of the heart in chest X‐ray, if needed. Amikacin was infused over 1 h. Peak and trough serum samples for amikacin were measured for all infants at steady state. Nephrotoxicity was assessed by serum creatinine and urinary N‐acetyl β‐d ‐glucosaminidase before and 7 days after therapy. Clinical efficacy was compared using both observation of clinical status and normalization of laboratory tests. Results: All the patients in group I had achieved a trough level <10 μg/mL and two patients had trough concentration >10 μg/mL in group II. No significant difference between group I and group II in either baseline or day 7 serum creatinine was demonstrated (P > 0·05). No significant difference was found between the two groups in clinical efficacy or renal toxicity. The calculated pharmacokinetic parameters were in group I and II, respectively: clearance =63·8 ± 15·9 mL/kg/h and 73·5 ± 18·1 mL/kg/h; volume of distribution =0·54 ± 0·09 L/kg and 0·61 ± 0·13 L/kg, half‐life =6·1 ± 1·0 h and 5·95 ± 1·1 h. What is new and conclusion: As expected, amikacin given once every 24 h to septic neonates of ≥36 weeks of gestation achieved higher peak levels and lower trough concentrations than the twice daily regimen. Treatment with once daily regimen did not lead to more nephrotoxicity than with a twice‐daily regimen, and showed comparable efficacy. 相似文献
5.
M. Campara PharmD S. S. Shord PharmD BCOP C. M. Haaf PharmD BCPS 《Journal of clinical pharmacy and therapeutics》2009,34(2):207-213
Background: The optimal rasburicase dose for adult patients has not been determined. Objective: To retrospectively examine use of rasburicase in our centre and to evaluate the effect of a single dose of rasburicase on urate and serum creatinine levels in our adult patients. Method: A retrospective chart review was conducted of all adult patients who received rasburicase for treatment of tumour lysis syndrome‐associated hyperuricaemia at our academic, urban medical centre from July 2002 to October 2006. Result: Twenty‐one patients received rasburicase with an average first dose of 0·15 ± 0·03 mg/kg. The drug dosing was calculated based on the patients’ ideal body weight (IBW) or adjusted body weight (aBW) for those who were more than 30% above their IBW. Patients experienced a mean serum urate reduction of 89·7 ± 9·0% from the baseline through the first 24 h after a single rasburicase dose (11·4 ± 4·5 mg/dL vs. 1·4 ± 1·4 mg/dL, respectively, P < 0·001). The urate levels remained within normal limits (<8 mg/dL) in all the patients for 48 h after a single dose of rasburicase. The major limitation of our study is that in 18 of 21 patients we lacked adequate documentation to ascertain that the blood samples sent for urate analysis after drug administration were handled according to the manufacturer’s recommendations. However, in this small group of patients, we observed that the effect of rasburicase on serum urate was similar to the total study population. The effect was sustained for 48 h after a single dose. Serum creatinine levels at 24–72 h after the single rasburicase dose were not significantly different from baseline (1·8 mg/dL vs. 2·3 mg/dL, respectively, P = 0·14). Conclusion: Rasburicase is an effective treatment for patients with hyperuricaemia and may aid in the prevention of hyperuricaemia‐associated nephrotoxicity. From our experience, a single dose of 0·15 mg/kg (IBW or aBW) of rasburicase appears to effectively decrease and maintain urate levels within normal limits for 48 h. 相似文献
6.
Fabio Silvio Taccone Pierre-Fran?ois Laterre Herbert Spapen Thierry Dugernier Isabelle Delattre Brice Layeux Daniel De Backer Xavier Wittebole Pierre Wallemacq Jean-Louis Vincent Frédérique Jacobs 《Critical care (London, England)》2010,14(2):R53
Introduction
It has been proposed that doses of amikacin of >15 mg/kg should be used in conditions associated with an increased volume of distribution (Vd), such as severe sepsis and septic shock. The primary aim of this study was to determine whether 25 mg/kg (total body weight) of amikacin is an adequate loading dose for these patients.Methods
This was an open, prospective, multicenter study in four Belgian intensive care units (ICUs). All consecutive patients with a diagnosis of severe sepsis or septic shock, in whom amikacin treatment was indicated, were included in the study.Results
In 74 patients, serum samples were collected before (t = 0 h) and 1 hour (peak), 1 hour 30 minutes, 4 hours 30 minutes, 8 hours, and 24 hours after the first dose of amikacin. Blood amikacin levels were measured by using a validated fluorescence polarization immunoassay method, and an open two-compartment model with first-order elimination was fitted to concentrations-versus-time data for amikacin (WinNonlin). In 52 (70%) patients, peak serum concentrations were >64 μg/ml, which corresponds to 8 times the clinical minimal inhibitory concentration (MIC) breakpoints defined by EUCAST for Enterobacteriaceae and Pseudomonas aeruginosa (S<8, R>16 μg/ml). Vd was 0.41 (0.29 to 0.51) L/kg; elimination half-life, 4.6 (3.2 to 7.8) hours; and total clearance, 1.98 (1.28 to 3.54) ml/min/kg. No correlation was found between the amikacin peak and any clinical or hemodynamic variable.Conclusions
As patients with severe sepsis and septic shock have an increased Vd, a first dose of ≥ 25 mg/kg (total body weight) of amikacin is required to reach therapeutic peak concentrations. However, even with this higher amikacin dose, the peak concentration remained below therapeutic target levels in about one third of these patients. Optimizing aminoglycoside therapy should be achieved by tight serum-concentration monitoring because of the wide interindividual variability of pharmacokinetic abnormalities. 相似文献7.
I. U. Rahman PhD Scholar S. A. Malik PhD M. Bashir MBBS FCPS R. U. Khan MD M. Idrees MBBS 《Journal of clinical pharmacy and therapeutics》2010,35(6):685-690
What is known and objective: Serum sialic acid is a recently investigated potential risk‐marker for cardiovascular complications. There is a known association between sialic acid and cardiovascular complications in diabetes mellitus. We aimed to investigate the effect of antidiabetic drugs on the serum concentration of sialic acid. Methods: We investigated the effect of metformin and rosiglitazone on the concentration of sialic acid in 120 type 2 diabetic patients, divided into a group (n = 60) receiving metformin and a group (n = 60) receiving rosiglitazone treatment. Results: Serum sialic acid was significantly higher in patients on rosiglitazone (66·90 ±8·80 mg/dL vs. 57·6 ± 8·46 mg/dL, P <0·01) and metformin (61·95 ± 10·49 mg/dL vs. 57·6 ±8·46mg/dL, P < 0·04) when compared with control subjects. In addition, rosiglitazone‐treated patients showed a significant increase in cardiovascular risk factors, notably total cholesterol (246·45 ± 20·2 mg/dL vs. 170·6 ± 15·1 mg/dL, P =0·01), triglyceride (178 ± 9·20 mg/dL vs. 149·35 ±6·31 mg/dL, P < 0·04) and glycohemoglobin (HbA1‐c) concentration (8·17 ± 1·43% vs. 4·38 ±0·96%, P < 0·02) compared with normal control subjects. The patients on metformin also showed significantly higher levels of serum glucose (133·7 ± 9·63 mg/dL vs. 88·35 ± 6·31 mg/dL, P <0·04) and glycohemoglobin (HbA1‐c) (8·23 ±1·75% vs. 4·38 ± 0·96%, P < 0·02) when compared with control subjects. Comparison of the two groups of patients revealed a significantly higher serum sialic acid (66·90 ± 8·80 mg/dL vs. 61·95 ±10·49 mg/dL, P < 0·05), total cholesterol (246·45 ±20·2 mg/dL vs. 192 ± 14·23 mg/dL, P <0·02) and triglyceride (178 ± 9·20 mg/dL vs. 158 ± 14·51mg/dL, P < 0·05) concentrations in the rosiglitazone‐treated patients. What is new and conclusions: This study suggests significantly higher levels of serum sialic acid and other cardiovascular risk factors in rosiglitazone‐treated patients than in metformin‐treated patients. The lower sialic acid concentration may explain a better metformin antidiabetic effect than with rosiglitazone. 相似文献
8.
M Chung L Parravicini B M Assael G Cavanna E Radwanski S Symchowicz 《Antimicrobial agents and chemotherapy》1982,22(6):1017-1021
The pharmacokinetics of netilmicin, gentamicin, and tobramycin in plasma and in perilymph of guinea pigs were studied after a single intravenous injection of 40 mg/kg. Detailed pharmacokinetic analysis of the plasma drug concentration-time data up to 36 h after the intravenous dose revealed that the pharmacokinetics of the aminoglycoside antibiotics can be best described as a three-compartment open model. The disposition half-lives (t1/2) in plasma of the three antibiotics were comparable and within the following ranges: t1/2 alpha of 0.09 to 0.16 h; t1/2 beta of 0.88 to 1.01 h; and t1/2 gamma of 7.87 to 8.29 h. The volume of distribution in the central compartment and the total body clearance of netilmicin (294 ml/kg, 5.74 ml/min per kg) were greater than those of gentamicin (160 ml/kg, 3.40 ml/min per kg) and tobramycin (204 ml/kg, 4.63 ml/min per kg). Pharmacokinetic analysis of the perilymph drug concentration-time data indicated that all three antibiotics penetrated the perilymph readily, but netilmicin cleared from the perilymph compartment faster than gentamicin and tobramycin. The maximum perilymph drug concentrations were 4.17, 8.05, and 6.78 micrograms/ml and occurred at 1, 2, and 4 h for netilmicin, gentamicin, and tobramycin, respectively. The ratio of area under the curve of perilymph to plasma was lowest for netilmicin (0.27), followed by gentamicin (0.39) and tobramycin (0.57). These results suggest that the differences in pharmacokinetics and concentrations of netilmicin in the perilymph may account for less ototoxic liability of netilmicin compared with gentamicin and tobramycin. 相似文献
9.
10.
Lee S Chung JY Hong KS Yang SH Byun SY Lim HS Shin SG Jang IJ Yu KS 《Journal of clinical pharmacy and therapeutics》2012,37(5):553-557
What is known and Objective: Acarbose, an α‐glycosidase inhibitor, is used to treat diabetic patients. Pharmacokinetic evaluation of acarbose is difficult because <2% is absorbed systemically. The current investigation evaluated the bioequivalence of two formulations of acarbose through pharmacodynamic comparison. Methods: This investigation consisted of a pilot study and a main study. The pilot study had an open, single‐dose, single‐sequence design. Subjects received placebo and then two tablets of reference formulation (Glucobay® 100 mg tablet; Bayer Healthcare) on two consecutive days with sucrose. The main study was an open, randomized, two‐period, two‐sequence crossover study. Subjects randomly received placebo and two tablets of either test formulation (generic acarbose 100‐mg tablet) or reference formulation with sucrose on two consecutive days in the first period. In the second period, placebo and alternative formulation were administered. Serial blood samples for pharmacodynamic assessment were taken after each administration. The maximum serum glucose concentration (Gmax) and the area under the serum glucose concentration–time profile (AUCgluc) were determined and compared. Results and Discussion: Five subjects completed the pilot study. The AUCgluc from dosing until 1 h post‐dose (AUCgluc,1 h) was significantly different between the placebo and acarbose. A total of 33 subjects completed the main study. The mean differences in Gmax (ΔGmax) and AUCgluc,1 h (ΔAUCgluc,1 h) for the reference formulation compared with placebo were 22·0 ± 18·3 mg/dL and 928·2 ± 756·0 mg min/dL, respectively. The corresponding values for the test formulation were 23·3 ± 21·2 mg/dL and 923·0 ± 991·4 0 mg min/dL, respectively. The geometric mean ratios (GMRs) of the test formulation to the reference formulation for ΔGmax and ΔAUCgluc,1 h were 1·06 and 1·00, respectively, and the 90% confidence intervals (CIs) corresponding values were 0·79–1·39 and 0·64–1·36, respectively. What is new and Conclusion: The 90% CIs of GMRs for the pharmacodynamic parameters chosen for bioequivalence evaluation of two formulations of acarbose did not meet the commonly accepted regulatory criteria for bioequivalence (0·80–1·25). 相似文献
11.
Hojo Y Echizenya M Ohkubo T Shimizu T 《Journal of clinical pharmacy and therapeutics》2011,36(6):711-715
What is known and objective: St John’s wort (SJW, Hypericum perforatum) is one of the most commonly used herbal antidepressants for treatment of mild to moderate depression. SJW enhances CYP3A4 activity and alters the pharmacokinetics of CYP3A4 substrates. This study investigated the effect of SJW on the pharmacokinetics of zolpidem in healthy subjects. Methods: A controlled, open‐label, non‐randomized, fixed‐dose schedule design was used. Fourteen healthy male subjects received a single 10 mg oral dose of zolpidem followed by SJW administration (300 mg orally, three times a day) for 14 days; the last dose of SJW was coadministered with a single dose of zolpidem. Blood samples were obtained over a 24‐h period after zolpidem administration. Pharmacokinetic data for zolpidem alone and in combination with SJW were analysed by high‐performance liquid chromatography. Results: After repeated administration of SJW, the mean values of AUC and Cmax for zolpidem significantly decreased (380·3 ± 181·4 vs. 265·4 ± 134·2 ng h/mL, P = 0·001; 83·1 ± 30·1 vs. 55·1 ± 24·8 ng/mL, P = 0·000 respectively) and the mean value of CL/F for zolpidem significantly increased (38·4 ± 31·5 vs. 56·9 ± 57·2 mL/min, P = 0·040). However, in three subjects, the AUC showed a small increase after SJW treatment. What is new and conclusion: The effect of SJW on the pharmacokinetics of zolpidem has not previously been reported. Repeated administration of SJW decreases the plasma concentration of zolpidem, probably by enhancing CYP3A4 activity. Given the wide inter‐subject variability observed, for personalized medicine, advice on the use of the combination should be individualized, based on the circumstances of the patient. 相似文献
12.
Feasibility of Administering Aminoglycoside Antibiotics by Continuous Intravenous Infusion 总被引:6,自引:6,他引:0
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Gerald P. Bodey Hui-Yen Chang Victorio Rodriguez Dorothy Stewart 《Antimicrobial agents and chemotherapy》1975,8(3):328-333
Eleven patients each received gentamicin sulfate, tobramycin, and sisomicin by continuous intravenous infusion after an initial loading dose. Subsequent doses of antibiotic were adjusted in an attempt to maintain constant serum concentrations. There was considerable variation in the serum concentration from patient to patient and in the same patient from day to day with each drug. Although the dosages of gentamicin sulfate and tobramycin were similar, the serum concentrations of the latter drug were consistently lower. Despite the daily administration of doses of at least 300 mg of gentamicin and tobramycin per m2 and 160 mg of sisomicin per m2, nephrotoxicity occurred in only three patients. This is a low frequency of nephrotoxicity, considering the dosages of drug administered. Although therapeutic efficacy was not an objective of this study, 8 of 11 documented infections were cured. This approach to the administration of aminoglycoside antibiotics deserves therapeutic trials. 相似文献
13.
Ten patients received a loading dose of tobramycin of 60 mg/m2 intravenously over 0.5 h followed immediately by 60 mg/m2 over 2 h every 4 h. The highest mean serum concentration (at the end of the loading dose) was 6.0 +/- 0.3 microgram/ml (range, 3.2 to 10.9 microgram/ml). The mean serum concentration 2 h after the end of the initial 2-h infusion was 3.0 +/- 0.2 microgram/ml (range, 1.6 to 3.9 microgram/ml). This schedule of tobramycin was used to treat 117 patients with presumed or proven infection. There were no differences in the mean serum concentrations of tobramycin at comparable times on days 3 to 4 and 6 to 7. Only 60% of patients had serum levels between 3 micrograms/ml (trough) and 10 micrograms/ml (peak). This intermittent schedule of administration resulted in substantial fluctuations in serum concentrations of tobramycin and produced trough concentrations which were too low or peak concentrations which were too high in some patients. 相似文献
14.
Objective: To find out whether polymyxin B-immobilized fiber (PMX-F) treatment affects the clinical parameters and plasma concentrations
of erythropoietin (EPO) and interleukin (IL)-6. Design: A prospective case series study. Setting: Intensive care unit of the Department of Internal Medicine, Misato Junshin Hospital, Saitama, and Koto Hospital, Tokyo, Japan.
Patients: 17 consecutive patients (10 men, 7 women; mean age 54.6 years) with clinically defined septic shock and 20 healthy volunteers
(12 men, 8 women; mean age 52.2 years). Main results: Of the 17 patients with septic shock, 9 (53 %) survived. The systolic blood pressure increased significantly from 78 ± 6
to 106 ± 8 mm Hg 2 h after PMX-F treatment in patients with septic shock. Plasma endotoxin levels decreased significantly
after treatment, from 40 ± 6 to 12 ± 4 pg/ml. The pretreatment plasma concentrations of EPO and IL-6 were significantly higher
in the 8 nonsurviving patients with septic shock (EPO: 400 ± 36 mlU/ml; IL-6: 6260 ± 1180 pg/ml) than in the 9 surviving patients
(EPO: 120 ± 22 mlU/ml; IL-6: 680 ± 138 pg/ml) and the 20 control subjects (EPO, 12 ± 6 mlU/ml; IL-6, 8 ± 2 pg/ml). Plasma
concentrations of EPO and IL-6 in patients with septic shock decreased significantly after PMX-F treatment (EPO, nonsurviving:
320 ± 28 mlU/ml, p < 0.05; survivors: 26 ± 8 mlU/ml, p < 0.001; IL-6, nonsurviving: 3860 ± 840 pg/ml, p < 0.01; survivors: 84 ± 20 pg/ml, p < 0.001). Conclusions: Plasma concentrations of EPO and IL-6 may be prognostic indicators in patients with septic shock: PMX-F treatment may be
effective in reducing the plasma concentrations of EPO and IL-6 in patients with septic shock.
Received: 11 February 1998 Accepted: 5 October 1998 相似文献
15.
Landa José I. Sánchez Jesús Alvarez Grau Montserrat Sánchez José A. Balibrea José L. 《Zeitschrift für die gesamte experimentelle Medizin einschliesslich experimenteller Chirurgie》1995,195(1):317-325
The role of tumor necrosis factor alpha (TNF) in the toxic and lethal effects of the endotoxemia associated with septic shock
is well known. This study was designed to establish whether natural somatostatin (SS-14) is capable of modifying the production
of TNF in a model of septic shock induced in the rat by bacterial lipopolysaccharide (LPS), and its theoretical relationship
to prostaglandin E2 (PGE2). An experimental study was carried out in 80 Wistar rats subjected to intravenous LPS injection. Perfusion of SS-14 at 2
μg/h or continuous isotonic saline (IS) at 0.1 ml/h started 30 min prior to LPS injection and continued until 90 min after.
All the animals were primed 15 days earlier with on intraperitoneal dose of BCG (2.2×107 CFU). ELISA assays were used to measure TNF levels after 90 min of perfusion and those of PGE2 at 30 and 90 min. The effects of two different doses of LPS (0.5 mg/kg of body weight and 5 mg/kg bw) were compared. SS-14
administration was associated with a decrease in TNF levels (1130.0±272.4 vs 4720.0±1278.1 pg/ml,p=0.013), and an increase in serum PGE2 basally (255.7±94.2 vs 62.0±10.6 pg/ml,P=0.04) and after 90 min of perfusion (1872.7±1250.6 vs 1009.7±612.0 pg/ml,P=NS), there being a statistically significant correlation between the basal PGE2 levels and these TNF after 90 min when compared using a regression model (r=−0.88,P=0.04 for the 0.5 mg/kg dose;r=−0.47,P=0.07 for 5 mg/kg). At 90 min, the level of TNF also depended on the PGE2 values (r=0.84,P=0.07 for 0.5 mg/kg;r=0.55,P=0.03 for 5 mg/kg). Multiple regression permitted TNF levels to be estimated on the basis of basal and 90 min PGE2 levels (P=0.03). Pretreatment with SS-14 led to a significant reduction of TNF and an increase of PGE2, there being an apparent correlation between the two. 相似文献
16.
A. J. SCHEEN A. C. FERREIRA ALVES de MAGALHAES T. SALVATORE P. J. LEFEBVRE 《European journal of clinical investigation》1994,24(Z3):50-54
In a double-blind cross-over study, we investigated a possible influence of the α-glucosidase inhibitor acarbose on the bioavailability of the biguanide compound metformin. Each of the six healthy young male volunteers was randomly allocated during two consecutive 7 day periods to either acarbose (days 1–3: 3 times 50mg day?1; days 4–7: 3 times 100 mg day?1) or placebo. At day 7 and 14 of the study, the overnight-fasted subjects ingested 1000mg metformin with the first bite of a standardized breakfast (500kcal; 60 g carbohydrates) and together with either placebo or 100 mg acarbose. Acarbose significantly (P < 0·05) reduced the meal-induced increase in blood glucose and plasma insulin levels. Acarbose induced a significant (P < 0·05) reduction in early (90, 120, 180min) serum levels, peak concentrations (Cmax: 1·22 ± 0·14 vs. 1·87 ± 0·60 mgl?1) and area under the curve of metformin (AUC 0–540min: 423±55 vs. 652±55 mg minl?1), but did not diminish its 24 h urinary excretion. In conclusion, acarbose significantly reduces the acute bioavailability of metformin in normal subjects. 相似文献
17.
G. Dumortier A. Lochu A. Zerrouk V. Van Nieuwenhuyse P. Colen de Melo D. Roche Rabreau K. Degrassat 《Journal of clinical pharmacy and therapeutics》1998,23(1):35-40
Background: Therapeutic drug monitoring of clozapine as an aid in the treatment of schizophrenic states is commonly used in our hospital. Objective: Development of a high-performance liquid chromatographic method for the deter?mination of clozapine (CLZ) and its major metabolite desmethylclozapine (DMCLZ) in plasma and saliva, and investigation of the relationship between plasma concentrations of CLZ and DMCLZ and concentrations in saliva in patients treated with clozapine. Methods: Subjects were either inpatients or outpatients with a DSM IV diagnosis of schizophrenia ( n=34). Determination of CLZ and DMCLZ saliva concentrations appeared to be a satisfactory method to check compliance to treatment, particularly in outpatients. Results: Mean CLZ and DMCLZ plasma concentrations were 432±264 ng/ml (±SD) (range 90–1310 ng/ml) and 257±144 ng/ml (range 55–580 ng/ml), respectively. The CLZ/DMCLZ plasma ratio was equal to 1·7±0·5 (daily dosage 7·2±2·3 mg/kg, n=34). Mean CLZ plasma and saliva levels were 336±157 ng/ml (range 90–580 ng/ml) and 159±86 ng/ml (range 40–364 ng/ml), respectively ( r=0·56, n=14). Mean DMCLZ plasma and saliva levels were 196±112 ng/ml (range 55–481 ng/ml) and 109±67 ng/ml (range 40–250 ng/ml), respectively ( r=0·73, n=14). Mean CLZ/DMCLZ ratios determined in plasma and saliva were 1·9±0·6 (range 1·0–3·4) and 1·7±0·6 (range 1·0–3·2), respectively ( r=0·85, n=14). CLZ and DMCLZ saliva concentrations appear to be useful for checking compliance to treatment, in particular among outpatients. 相似文献
18.
Huang HC Chang YL Lan TH Chiu HJ Liu WM Lee TJ 《Journal of clinical pharmacy and therapeutics》2008,33(2):115-121
Background: Standard dosing regimens with lithium usually require significant time before the optimal serum concentration is achieved. Method: The present study compares a new method (Method 1) with two existing ones (Methods 2 and 3) for dosing of individual patients with lithium, to more rapidly achieve optimum concentrations. Thirty patients, who were on lithium therapy and who met the inclusion criteria, were evaluated. Results: The correlation coefficient between true and expected concentrations were 0·518 (P < 0·01), 0·555 (P < 0·01) and 0·424 (P = 0·019) respectively. The mean ± standard deviation of the difference from the expected concentrations of three methods were 0·02 ± 0·20 mEq/L, 0·31 ± 0·22 and ?0·27 ± 0·25 respectively. Conclusion: Method 1 was the least biased and most accurate among three methods for predicting the optimal therapeutic lithium dose in Taiwanese psychiatric patients. 相似文献
19.
P. HüUttemeier K. Eliasen T. Mogensen M. Bell J. NSrtved SSrensen J. Ovist 《Clinical physiology and functional imaging》1986,6(5):415-422
Summary. We investigated the effect of a thromboxane antagonist, BM 13·177, during endotoxin-induced pulmonary vasoconstriction in sheep. In control animals intravenous E-coli endotoxin (1 μg/kg) caused a transient increase of pulmonary artery and airway pressure paralleled by large concentration increases of TXB2: in comparison peak plasma concentrations of 6-keto-PGFlα (a prostacyclin metabolite) were small and delayed in time. Pre-treatment with BM 13·177 (bolus 5 mg/kg), followed by 0·75 mg/kg/min intravenously) abolished the rise of pulmonary artery and airway pressure. Plasma concentrations of TXB2 and 6-keto-PFGla were similar to controls. These and previous investigations imply that BM 13·177 specifically antagonizes TXA2 on the putative receptor in pulmonary vascular and airway smooth muscle. 相似文献
20.
A. M. Almeida A. C. Falco F. Sales F. Leito J. Santos I. M. Costa M. M. Caramona 《Journal of clinical pharmacy and therapeutics》1998,23(4):315-321
Objective : The aim of our work was to define the kinetic profile of carbamazepine (CBZ), in order to improve on dosing schedules through a Bayesian approach. Method: Carbamazepine dose/steady-state trough concentrations data pairs and associated information were collected retrospectively on a population of adult epileptic patients. Results: Fifty patients (index population) with two or more available concentrations (total of 174 determinations) met our inclusion criteria. Patients were taking CBZ (200–1800 mg/day) in mono- or polytherapy regimens. The analysis assumed a one-compartimental model with first-order absorption and elimination. Due to the data source (only trough concentrations were measured as part of hospital routine), the volume of distribution was fixed at 1·19 l/kg. The final estimates for CL were: 0·075± 0·027 (mono- and polytherapy), 0·069±0·020 (monotherapy), and 0·106±0·037 l/h/kg (poly?therapy). In order to validate these results, we assessed their predictive capacity using 18 new patients (validation population), submitted to the same inclusion criteria and using Prediction-Error analysis. The results suggested a different CL value for our population compared to earlier published clearance values. The results also pointed to an increased metabolic rate associated with polytherapy. The prediction capacity of the optimization method derived from a Portuguese population made in an a priori evaluation indicated a low error (–0·04 μg/ml), close to the theoretical zero value. Conclusion: Our results provide specific data on CBZ disposition in a Portuguese population and given the wide variability in the literature values, our data may help improve dosing of CBZ in Portuguese patients. 相似文献