|
1. |
Report of a survey of some aspects of editorial board peer review at Clinical Pharmacology and Therapeutics |
|
Clinical Pharmacology&Therapeutics,
Volume 50,
Issue 1,
1991,
Page 1-3
June W Reidenberg,
Marcus M Reidenberg,
Preview
|
PDF (195KB)
|
|
摘要:
Clinical Pharmacology and Therapeutics(1991)50, 1–3; doi:10.1038/clpt.1991.
ISSN:0009-9236
DOI:10.1038/clpt.1991.96
年代:1991
数据来源: WILEY
|
2. |
The intellectual health of clinical drug evaluation |
|
Clinical Pharmacology&Therapeutics,
Volume 50,
Issue 1,
1991,
Page 4-9
Lewis B Sheiner,
Preview
|
PDF (401KB)
|
|
摘要:
Clinical Pharmacology and Therapeutics(1991)50, 4–9; doi:10.1038/clpt.1991.
ISSN:0009-9236
DOI:10.1038/clpt.1991.97
年代:1991
数据来源: WILEY
|
3. |
Increased carbamazepine plasma concentrations after fluoxetine coadministration |
|
Clinical Pharmacology&Therapeutics,
Volume 50,
Issue 1,
1991,
Page 10-15
Sara R Grimsley,
Michael W Jann,
J Gary Carter,
Anil P D'mello,
Martin J D'souza,
Preview
|
PDF (310KB)
|
|
摘要:
The interaction between fluoxetine and carbamazepine was investigated in six normal, healthy male volunteers (aged 23 to 40 years). Subjects were given carbamazepine, 400 mg every morning, for 3 weeks. Venous carbamazepine blood samples were obtained at baseline and 1, 2, 4, 6, 8, 10, 12, and 24 hours after the morning dose. Fluoxetine, 20 mg every morning, was then coadministered with carbamazepine for 7 days. Venous carbamazepine blood samples were again obtained as described. Carbamazepine and carbamazepine‐10,11‐epoxide (CBZE) were assayed by HPLC. Addition of fluoxetine resulted in a significant increase in the area under the concentration‐time curve of carbamazepine (105.93 ± 18.05 μg/ml · hr versus 134.97 ± 12.15 μg/ml · hr;t= 3.284;df= 5;p= 0.022) and CBZE (11.6 ± 1.93 μg/ml · hr versus 15.2 ± 2.4 μg/ml · hr;t= 2.805;df= 5;p= 0.038). Both oral and intrinsic clearance of carbamazepine was decreased significantly on fluoxetine addition (3.87 ± 0.68 L/hr versus 2.98 ± 0.26 L/hr;t= 3.025;df=5;p= 0.029 and 17.90 ± 4.9 L/hr versus 11.92 ± 1.4 L/hr;t= 3.037;df= 5;p= 0.029, respectively). No significant changes were determined for fraction of absorbed dose, volume of distribution, absorption rate constant, and elimination rate constant. These findings suggest that fluoxetine can inhibit the metabolism of carbamazepine. Careful monitoring of patients is recommended when these two drugs are coadministered.Clinical Pharmacology and Therapeutics(1991)50, 10–15;
ISSN:0009-9236
DOI:10.1038/clpt.1991.98
年代:1991
数据来源: WILEY
|
4. |
The influence of dosage time of midazolam on its pharmacokinetics and effects in humans |
|
Clinical Pharmacology&Therapeutics,
Volume 50,
Issue 1,
1991,
Page 16-24
Richard Koopmans,
Jasper Dingemanse,
Meindert Danhof,
Gerard P M Horsten,
Chris J Boxtel,
Preview
|
PDF (500KB)
|
|
摘要:
The influence of dosage time of midazolam on its pharmacokinetics and effects on the central nervous system were investigated in six healthy volunteers, with pharmacokinetic‐pharmacodynamic modeling. Each volunteer received single oral doses of 15 mg midazolam on four separate occasions: 8 AM, 2 PM, 8 PM, and 2 AM. An almost significant circadian variation was found in elimination half‐life, shortest at 2 PM (1.26 ± 0.47 hours, mean ± SD) and longest at 2 AM (1.57 ± 0.44 hours) (p= 0.05). Drug effects measured were α activity of the electroencepalograph and P100 latency of the visual‐evoked response. The maximum drug effect (Emax) model described the concentration‐effect relationship, extended with either a threshold drug concentration or a sigmoidicity parameter. A significant circadian variation was found in baseline α activity: highest at 8 AM (109% ± 19% of the 24‐hour mean) and lowest at 2 AM (80% ± 12%). For α activity the drug concentration at half‐maximum effect of both threshold Emaxmodel and sigmoid Emaxmodel showed lower values at 8 AM and 2 AM and higher values at 2 PM and 8 PM. However, these differences were either not significant (p= 0.10, threshold model) or on the verge of statistical significance (p= 0.05, sigmoid model). No circadian variation was found in the parameters describing the effect on the visual‐evoked response. We conclude that the sensitivity of the central nervous system to midazolam, as reflected in α activity, possibly shows a circadian variation.Clinical Pharmacology and Therapeutics(1991)50, 16–24;
ISSN:0009-9236
DOI:10.1038/clpt.1991.99
年代:1991
数据来源: WILEY
|
5. |
Gentamicin population pharmacokinetic models for low birth weight infants using a new nonparametric method |
|
Clinical Pharmacology&Therapeutics,
Volume 50,
Issue 1,
1991,
Page 25-31
Warren F Dodge,
Roger W Jelliffe,
C Joan Richardson,
Renee A McCleery,
James A Hokanson,
Wayne R Snodgrass,
Preview
|
PDF (417KB)
|
|
摘要:
Availability of personal computer programs for control of drug regimens has stimulated interest in modeling population pharmacokinetics. In this study, we found parameter values for gentamicin in two infant populations with low birth weights. The models were developed by use of a parametric (i.e., standard two‐stage algorithm) and with a new nonparametric expected maximum algorithm. Data for the two populations (i.e., infants ≤31 weeks' and>31 but ≤34 weeks' gestational age) were obtained from infants admitted to the University of Texas Medical Branch intensive care nursery between August 1, 1988, and July 31, 1989. The new nonparametric method was demonstrated to be not only the equal of the standard two‐stage method for population modeling but better, especially in use of sparse data sets (e.g., single serum levels). It also obviates the need for selecting proper starting conditions for the least‐squares fitting procedure used in the standard two‐stage method.Clinical Pharmacology and Therapeutics(1991)50, 25–31; doi:10.1038
ISSN:0009-9236
DOI:10.1038/clpt.1991.100
年代:1991
数据来源: WILEY
|
6. |
Doxapram metabolism in human fetal hepatic organ culture |
|
Clinical Pharmacology&Therapeutics,
Volume 50,
Issue 1,
1991,
Page 32-38
Aida Bairam,
Charlotte Branchaud,
Kay Beharry,
Joan Rex,
Nicole Laudignon,
Apostolos Papageorgiou,
Jacob V Aranda,
Preview
|
PDF (376KB)
|
|
摘要:
The biotransformation of doxapram, a respiratory stimulant was studied with use of explants from human fetal livers (n= 15 fetuses) obtained from therapeutic abortions (gestational age, 10 to 20 weeks). Explants were cultured in Leibowitz medium and the media from cultured samples were collected before and at 3, 6, 12, and 24 hours after incubation with 2.5, 5.0, and 10 μg/ml doxapram. The concentrations of doxapram and its metabolites (AHR 0914, an analog of doxapram, AHR 5955 or ketodoxapram, and AHR 5904) were measured by high pressure liquid chromatography. Explant histopathology and alkaline phosphatase activity showed no direct toxic effects of the drug on liver tissue. The fastest rate of doxapram metabolism occurred during the first 3 hours of incubation (198 ± 73.3, 438 ± 63.3, and 538 ± 62 ng/mg/hr liver protein at doxapram concentrations of 2.5, 5.0, and 10.0 μg/ml, respectively). At 3 hours of incubation, the amount of doxapram metabolized (nanogram per milligram of liver protein) was significantly higher (p<0.01) at doxapram concentrations of 10.0 (1616 ± 186) and 5.0 μg/ml (1315 ± 190) than at 2.5 μg/ml (594 ± 220). The oxidative pathway producing keto‐doxapram, or AHR 5955 and AHR 5904, is more active than the de‐ethylation producing the analog of doxapram AHR 0914. Data indicate substantial metabolism of doxapram by the human fetal liver.Clinical Pharmacology and Therapeutics(1991)50, 32–38; doi:10.10
ISSN:0009-9236
DOI:10.1038/clpt.1991.101
年代:1991
数据来源: WILEY
|
7. |
Exploratory analysis of population pharmacokinetic data from clinical trials with application to isradipine |
|
Clinical Pharmacology&Therapeutics,
Volume 50,
Issue 1,
1991,
Page 39-54
Robert Laplanche,
Bernard Fertil,
Erich Nüesch,
Jean‐Philippe Jais,
Werner Niederberger,
Jean‐Louis Steimer,
Preview
|
PDF (2957KB)
|
|
摘要:
Drug level monitoring during routine clinical visits in the course of phase III trials provides a means to document pharmacokinetic variability in a patient population. Such a pharmacokinetic screen was performed for the new calcium antagonist isradipine. A total of 697 blood samples were collected at any time after the morning dose from 252 patients who had received oral doses of isradipine. Three approaches of data analysis based on exploratory (graphical and statistical) techniques were used to relate plasma level to patient demographic data and laboratory parameters. The pharmacokinetics of isradipine seemed to be influenced by the demographic variables of age (already detected in conventional studies) and weight, as well as by the blood serum levels of inorganic phosphorous, uric acid, alkaline phosphatase, and bilirubin, but only to a small, clinically irrelevant extent. The findings from the three approaches were complementary. They suggest that a pharmacokinetic screening in clinical trials is feasible at reasonable experimental cost and effort and provides useful data on interindividual and intraindividual pharmacokinetic variability in patients.Clinical Pharmacology and Therapeutics(1991)50, 39–54; doi:10.1038/clpt.1991.1
ISSN:0009-9236
DOI:10.1038/clpt.1991.102
年代:1991
数据来源: WILEY
|
8. |
Netilmicin in the neonate: Population pharmacokinetic analysis and dosing recommendations |
|
Clinical Pharmacology&Therapeutics,
Volume 50,
Issue 1,
1991,
Page 55-65
Karin Fattinger,
Samuel Vozeh,
Arni Olafsson,
Jiri Vlcek,
Markus Wenk,
Ferenc Follath,
Preview
|
PDF (539KB)
|
|
摘要:
Netilmicin pharmacokinetics were studied in neonates of 27 to 42 weeks' gestational age and 0.8 to 5.0 kg body weight in their first 2 weeks of life by the population pharmacokinetic approach. The data were best described by a two‐compartment model. Clearance depends on body weight, gestational age, and postnatal age. Volume of distribution of the central and peripheral compartments was also related to body weight. Including these patient characteristics in the population pharmacokinetic regression model resulted in a marked reduction of the unexplained interindividual variability. This enabled us to derive dosage recommendations that result in peak and average concentrations within the desired range for 95% of the neonates with gestational age above 31 weeks, thus avoiding the need for individual drug‐level monitoring in a well‐defined large group of patients. Only for infants with gestational age less than 31 weeks who are less than 6 days old is individual dose adjustment based on serum concentration measurements required.Clinical Pharmacology and Therapeutics(1991)50, 55–65; doi:10.1038/clpt.
ISSN:0009-9236
DOI:10.1038/clpt.1991.103
年代:1991
数据来源: WILEY
|
9. |
Tolerance to nicotinic acid flushing |
|
Clinical Pharmacology&Therapeutics,
Volume 50,
Issue 1,
1991,
Page 66-70
Ralph H Stern,
J David Spence,
David J Freeman,
Anwar Parbtani,
Preview
|
PDF (266KB)
|
|
摘要:
The mechanism of tolerance to nicotinic acid flushing was determined in subjects during a 5‐day course of treatment. Objective measures of skin blood flow were used to confirm the development of tolerance. Plasma levels of nicotinic acid showed marked intraindividual variability but were not decreased with the development of tolerance. However plasma levels of 9‐α 11‐β prostaglandin F2, a stable metabolite of prostaglandin D2, became undetectable in most subjects with the development of tolerance. Thus tolerance is not associated with decreased levels of nicotinic acid or development of tolerance to the prostaglandin mediator, but with decreased levels of the mediator.Clinical Pharmacology and Therapeutics(1991)50, 66–70; doi:10.1038/clp
ISSN:0009-9236
DOI:10.1038/clpt.1991.104
年代:1991
数据来源: WILEY
|
10. |
Assessment of MK‐467, a peripheral α2‐adrenergic receptor antagonist, with intravenous clonidine |
|
Clinical Pharmacology&Therapeutics,
Volume 50,
Issue 1,
1991,
Page 71-77
John B Warren,
Colin T Dollery,
David Sciberras,
Michael R Goldberg,
Preview
|
PDF (360KB)
|
|
摘要:
The activity of MK‐467, a new peripherally acting α2‐antagonist was assessed in volunteers by a randomized, double‐blind, crossover design. One hour after administration of either 15 mg or 30 mg MK‐467 or placebo, 200 μg clonidine was given intravenously and observations were made for a further 8 hours. Clonidine reduced plasma norepinephrine levels to 79% ± 7% of that of control 1 hour after infusion, an effect that was antagonized by low‐dose MK‐467 (p<0.05). Mean systolic blood pressure increased by 4 mm Hg in the first hour after the 30 mg dose of MK‐467 (p<0.01), although there was no significant difference between the 3 study days in the maximal clonidine‐induced decrease in systolic pressure, diastolic pressure, or heart rate. Clonidine induced a peak increase in mean blood glucose of 13%, which was antagonized by both doses of MK‐467 (p<0.05). Plasma insulin was suppressed by clonidine from 72 ± 14 to 47 ± 7 IU · L−1, an effect antagonised by both doses of MK‐467 (p<0.05 in each case). MK‐467 had no effect on clonidine‐induced increased drowsiness, xerostomia, or increase in growth hormone secretion, which is consistent with it being a peripherally acting specific α2‐antagonist. The small effect of MK‐467 on clonidine‐induced changes in plasma glucose and insulin suggests that peripheral α2‐adrenergic receptors play only a minor role in normal glucose homeostasis.Clinical Pharmacology and Therapeutics
ISSN:0009-9236
DOI:10.1038/clpt.1991.105
年代:1991
数据来源: WILEY
|
|