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1. |
Primum non nocere?Valuing of the risk of drug toxicity in therapeutic decision making |
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Clinical Pharmacology&Therapeutics,
Volume 53,
Issue 3,
1993,
Page 285-291
Leslie A Lenert,
Daniel R Markowitz,
Terrence F Blaschke,
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摘要:
Clinical Pharmacology and Therapeutics(1993)53,285–291; doi:10.1038/clpt.1993.
ISSN:0009-9236
DOI:10.1038/clpt.1993.23
年代:1993
数据来源: WILEY
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2. |
Cations in the didanosine tablet reduce ciprofloxacin bioavailability |
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Clinical Pharmacology&Therapeutics,
Volume 53,
Issue 3,
1993,
Page 292-297
Jan Sahai,
Keith Gallicano,
Linda Oliveras,
Shireen Khaliq,
Nanci Hawley‐Foss,
Gary Garber,
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摘要:
The effect of the magnesium‐aluminum cations contained in didanosine chewable tablets on ciprofloxacin pharmacokinetics was evaluated in 12 healthy volunteers. The study was designed as a randomized, balanced, open, two‐period, two‐treatment crossover trial with a 7‐day washout period between treatments. In one phase, subjects received a single 750 mg ciprofloxacin tablet alone. In the didanosine‐cation regimen, subjects received two didanosine‐placebo tablets every 12 hours for two doses. On day 2, they received two didanosine‐placebo tablets immediately followed by a single 750 mg ciprofloxacin tablet. Serial blood samples were collected for 24 hours after administration of each ciprofloxacin dose. The average maximum concentration of ciprofloxacin alone was 3.38 ± 0.63 (SD) µg/ml compared with 0.25 ± 0.21 (SD) µg/ml when ciprofloxacin was administered with the didanosine placebo(p<0.0001). The mean (± SD) area under the plasma drug concentration–time curve from time 0 to the last measurable concentration for ciprofloxacin alone was 15.50 ± 2.69 µg · hr/ml compared with 0.26 ± 0.21 µg · hr/ml when ciprofloxacin was coadministered with the didanosine‐placebo(p<0.0001). The mean time to maximum concentration of ciprofloxacin alone decreased from 1.56 ± 0.62 to 0.75 ± 0.38 hours with buffer administration(p= 0.0012). The simultaneous administration of ciprofloxacin and didanosine should be avoided.Clinical Pharmacology and Therapeutics(1993)53,29
ISSN:0009-9236
DOI:10.1038/clpt.1993.24
年代:1993
数据来源: WILEY
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3. |
A potentially hazardous interaction between erythromycin and midazolam |
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Clinical Pharmacology&Therapeutics,
Volume 53,
Issue 3,
1993,
Page 298-305
Klaus T Olkkola,
Kari Aranko,
Harri Luurila,
Arja Hiller,
Laila Saarnivaara,
Jaakko‐Juhani Himberg,
Pertti J Neuvonen,
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摘要:
Interaction between erythromycin and midazolam was investigated in two double‐blind, randomized, crossover studies. In the first study, 12 healthy volunteers were given 500 mg erythromycin three times a day or placebo for 1 week. On the sixth day, the subjects ingested 15 mg midazolam. In the second study, midazolam (0.05 mg/kg) was given intravenously to six of the same subjects, after similar pre‐treatments. Plasma samples were collected, and psychomotor performance was measured. Erythromycin increased the area under the midazolam concentration–time curve after oral intake more than four times(p<0.001) and reduced clearance of intravenously administered midazolam by 54%(p<0.05). In psychomotor tests (e.g., saccadic eye movements), the interaction between erythromycin and orally administered midazolam was statistically significant(p<0.05) from 15 minutes to 6 hours. Metabolism of both erythromycin and midazolam by the same cytochrome P450IIIA isozyme may explain the observed pharmacokinetic interaction. Prescription of midazolam for patients receiving erythromycin should be avoided or the dose of midazolam should be reduced by 50% to 75%.Clinical Pharmacology and Therapeutics(1993)53,298–305; doi:10.1038/clpt
ISSN:0009-9236
DOI:10.1038/clpt.1993.25
年代:1993
数据来源: WILEY
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4. |
Measurement of in vivo microsomal epoxide hydrolase activity in white subjects |
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Clinical Pharmacology&Therapeutics,
Volume 53,
Issue 3,
1993,
Page 306-315
Deanna L Kroetz,
Bradley M Kerr,
Lynne V McFarland,
Pierre Loiseau,
Alan J Wilensky,
René H Levy,
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摘要:
An impairment or hereditary defect in microsomal epoxide hydrolase is considered a possible risk factor for drug and chemical toxicity. However, nothing is known about variability of in vivo epoxide hydrolase activity in humans. Our objectives were to develop and test a simple pharmacokinetic approach for measuring microsomal epoxide hydrolase activity in a population. After administration of carbamazepine‐10,11 ‐epoxide (100 mg), oral clearance showed a nearly linear relationship to the log (transdihydrodiol/epoxide) urine ratio in the 24‐ to 36‐hour interval (log metabolic ratio). Intrasubject variability was assessed by administering the epoxide twice to 13 subjects (1‐ to 4‐month interval); the log metabolic ratio did not change significantly (mean difference, 11%; pairedttest,p= 0.79). In 110 healthy white adults, the log metabolic ratio ranged from 1.28 to 2.05 (mean ± SD, 1.68 ± 0.155). Outliers indicating enzyme‐deficient phenotypes were not observed, and the frequency distribution was unimodal normal. The log metabolic ratio detected pronounced inhibition of epoxide hydrolase by val‐promide (six subjects; median ratio, 0.91) and induction by phenobarbital/phenytoin (six subjects; median ratio, 2.42). We conclude that distribution of microsomal epoxide hydrolase activity in a study group can be measured pharmacokinetically by use of carbamazepine epoxide.Clinical Pharmacology and Therapeutics(1993)53,306–315; doi:
ISSN:0009-9236
DOI:10.1038/clpt.1993.26
年代:1993
数据来源: WILEY
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5. |
Nicotine and cotinine elimination pharmacokinetics in smokers and nonsmokers |
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Clinical Pharmacology&Therapeutics,
Volume 53,
Issue 3,
1993,
Page 316-323
Neal L Benowitz,
Peyton Jacob,
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摘要:
Published research suggests that smokers metabolize nicotine and its major metabolite cotinine more rapidly than nonsmokers. To evaluate this possibility, we studied the disposition pharmacokinetics of intravenous deuterium‐labeled nicotine in 11 smokers (administered 2.0 and 0.5 µg/kg/min × 30 minutes) and in 11 nonsmokers (0.5 µg/kg/min). Smokers did not metabolize nicotine more rapidly; the clearance of nicotine normalized for body weight was significantly slower in smokers than in nonsmokers. Cotinine elimination rates were similar in the two groups. The disposition pharmacokinetics of nicotine was similar for the low and high doses in the smokers, indicating that metabolism is dose‐independent. Our findings argue against “metabolic tolerance” as a mechanism for the dose escalation observed in smokers after initiation of smoking. Our findings suggest that nicotine and cotinine kinetic parameters for smokers may be extrapolated to nonsmokers for estimating exposures to environmental tobacco smoke in nonsmokers.Clinical Pharmacology and Therapeutics(1993)53,316–323; doi:10.1038
ISSN:0009-9236
DOI:10.1038/clpt.1993.27
年代:1993
数据来源: WILEY
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6. |
Pharmacokinetics of prednisolone transfer to breast milk |
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Clinical Pharmacology&Therapeutics,
Volume 53,
Issue 3,
1993,
Page 324-328
Paul A Greenberger,
Yaseen K Odeh,
Marilynn C Frederiksen,
Arthur J Atkinson,
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摘要:
Prednisolone transfer to breast milk was studied in three nursing women who required oral steroid therapy for asthma. Each patient received a 50 mg intravenous dose of prednisolone phosphate, and blood and breast milk were sampled for 6 hours. Concentrations of prednisolone in milk declined more rapidly than in serum but were similar to expected unbound serum concentrations, suggesting that exchange between unbound prednisolone in serum and breast milk is relatively rapid and bidirectional. Because an average of 0.025% (range, 0.010% to 0.049%) of the prednisolone dose was recovered in milk, prednisolone transfer to breast milk does not appear to pose a clinically significant risk to nursing infants.Clinical Pharmacology and Therapeutics(1993)53,324–328; doi:10.1038/clpt.1993.
ISSN:0009-9236
DOI:10.1038/clpt.1993.28
年代:1993
数据来源: WILEY
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7. |
The transfer of cocaine and its metabolites across the term human placenta |
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Clinical Pharmacology&Therapeutics,
Volume 53,
Issue 3,
1993,
Page 329-339
Steven Schenker,
Yiqian Yang,
Raymond F Johnson,
John W Downing,
Robert S Schenken,
George I Henderson,
Thomas S King,
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摘要:
This study defines human placental transport of cocaine and its two minor, but pharmacologically active, metabolites—norcocaine and cocaethylene. The experimental system was the single, isolated perfused cotyledon of a normal term human placenta, and antipyrine served as a freely diffusible marker. Cocaine was transferred rapidly by the placenta at a rate about 80% that of antipyrine. The transfer had characteristics of passive transport consistent with the high lipid solubility of the drug. We found no evidence of significant placental metabolism of cocaine during its rapid placental transfer. Ethanol did not alter the cocaine transfer rate. Norcocaine and cocaethylene were equally as rapidly transferred. Thus the placenta is no barrier to the transfer of cocaine and its derivatives to the fetus.Clinical Pharmacology and Therapeutics(1993)53,329–339; doi:10.1038/clpt.199
ISSN:0009-9236
DOI:10.1038/clpt.1993.29
年代:1993
数据来源: WILEY
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8. |
Influence of aging on the pharmacokinetics and pharmacodynamics of doxacurium |
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Clinical Pharmacology&Therapeutics,
Volume 53,
Issue 3,
1993,
Page 340-347
L P Gariepy,
F Varin,
F Donati,
Y Salib,
D R Bevan,
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摘要:
Doxacurium (30 µg/kg) pharmacokinetics and pharmacodynamics were evaluated in nine elderly (age range, 70 to 83 years) and nine young (age range, 19 to 39 years) patients under nitrous oxide–isoflurane anesthesia. The force of contraction of the adductor pollicis was monitored and plasma samples were collected for an 8‐hour period. In the elderly group, doxacurium elimination half‐life was prolonged (119.7 versus 75.9 minutes) and plasma clearance was significantly reduced (1.75 versus 2.54 ml/min/kg) without any change in volume of distribution. Onset (12.9 versus 8.9 minutes) and recovery times (113.4 versus 48.1 minutes) were longer in the elderly group. The equilibrium rate constant to the effect compartment (keo) was decreased in the elderly (0.039 versus 0.051 min−1), whereas the effect compartment concentration at 50% block was similar in both groups (44.7 versus 54.1 ng/ml). An age‐related reduction in muscle blood flow may be responsible for the decrease in keo. The pharmacokinetic changes observed in the elderly are consistent with a decreased function in the organs of elimination.Clinical Pharmacology and Therapeutics(1993)53,340–347; doi:10.1038
ISSN:0009-9236
DOI:10.1038/clpt.1993.30
年代:1993
数据来源: WILEY
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9. |
Thiopurine methyltransferase activity in a sample population of black subjects in Florida |
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Clinical Pharmacology&Therapeutics,
Volume 53,
Issue 3,
1993,
Page 348-353
Carolyn D Jones,
Cameale Smart,
Albert Titus,
Gershwin Blyden,
Marie Dorvil,
Naomi Nwadike,
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摘要:
Thiopurine methyltransferase (TPMT), is an enzyme detected in the human red blood cell that catalyzes theS‐methylation of thiopurine drugs and is known to exist as a genetic polymorphism in white subjects. Investigations in this laboratory of red blood cell TPMT showed interethnic differences also existed in North American black subjects. A sample group of black subjects in Florida had a mean activity of 8.64 ± 3.47 U/ml red blood cells and an antimode of 6.5 units, which represented values significantly lower than those obtained for both the mean activity and the antimode in other populations. The findings of this study suggest the possibility that TPMT activity may be under genetic control in North American black subjects and that this ethnic group may be at greater risk of experiencing thiopurine‐induced toxicity caused by the lower overall mean activity of the enzyme.Clinical Pharmacology and Therapeutics(1993)53,348–353; doi:10.1038/clpt.
ISSN:0009-9236
DOI:10.1038/clpt.1993.31
年代:1993
数据来源: WILEY
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10. |
Quinidine interaction with nifedipine and felodipine: Pharmacokinetic and pharmacodynamic evaluation |
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Clinical Pharmacology&Therapeutics,
Volume 53,
Issue 3,
1993,
Page 354-359
David G Bailey,
David J Freeman,
Libardo J Melendez,
John H Kreeft,
Boo Edgar,
S George Carruthers,
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摘要:
Conflicting findings suggest that serum quinidine concentrations may be decreased or increased by nifedipine. We performed a double‐blind, placebo‐controlled trial of Latin‐square design. Twelve healthy men received 3 days of pretreatment with nifedipine prolonged action (20 mg twice a day) or felodipine extended release (10 mg every day), another dihydropyridine calcium antagonist, followed by coadministration of quinidine (400 mg). Quinidine pharmacokinetics were not changed by either dihydropyridine. However, 3‐hydroxyquinidine area under the concentration‐time curve (AUC) and 3‐hydroxyquinidine/quinidine AUC ratio were decreased by felodipine, consistent with reduced metabolite formation. Heart rates and adverse events were higher with felodipine, demonstrating lack of bioequivalence with nifedipine. The QTcinterval did not deviate from that expected for the observed quinidine concentration, suggesting the pharmacokinetics of active quinidine metabolites were not markedly altered among treatments. Quinidine disposition did not appear to be changed sufficiently to be clinically important by sustained‐release nifedipine and felodipine.Clinical Pharmacology and Therapeutics(1993)53,354–359; doi:10.1
ISSN:0009-9236
DOI:10.1038/clpt.1993.32
年代:1993
数据来源: WILEY
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