Abstract:
OBJECTIVES:To assess relative roles of the intestinal and hepatic stereoselective metabolism of nicardipine in an oral first-pass disposal with and without grapefruit juice intake. METHODS:The kinetic profiles of (+)- and (-)-nicardipine were studied in the six normal healthy male volunteers who received oral (40 mg) and intravenous (2 mg) racemic nicardipine, first with water and second with grapefruit juice. Both the enantiomers were determined by the stereoselective high-performance liquid chromatographic method, and hemodynamic parameters (arterial blood pressure, heart rate, and electrocardiogram) were assessed when each blood sample was taken. RESULTS:Grapefruit juice compared with water intake caused a significant (P < 0.05) increase in the mean oral (+)- and (-)-nicardipine bioavailability (Fobs) (48.6+/-5.0% and 105.6+/-7.8%) and dose-absorbed (Fabs) available fraction unmetabolized at the gut (Fg) (48.2+/-5.6% and 110.9+/-8.8%, respectively) with no significant change in the hepatic first-pass effect. However, all of the mean kinetic parameters of both the enantiomers after the intravenous dosing of racemic nicardipine did not differ between the grapefruit juice- and water-intake trial phases. The mean percentage changes in oral AUC (43.1+/-3.4% in [+]-nicardipine and 90.9 6.4% in [-]-nicardipine, or Fobs) and Fabs Fg by grapefruit juice tended to be greater for (-)-nicardipine than for (+)-nicardipine and the mean oral (+)/(-)-nicardipine AUC ratio was significantly reduced by grapefruit juice (from 2.25+/-0.37 to 1.75+/-0.28) (P < 0.05). Except for heart rates, which were greater with grapefruit juice (P < 0.05) at 1 and 2 h after the oral dose of nicardipine, the mean hemodynamic variables did not differ between the two trial phases. CONCLUSION:We conclude that the gut is the major presystemic disposal site of racemic nicardipine in humans. Grapefruit juice appears to affect this metabolic disposal of (-)-nicardipine to a somewhat greater extent compared with that of (+)-nicardipine, with an early postdose transient tachycardia after the oral dosing of racemic nicardipine.
journal_name
Eur J Clin Pharmacoljournal_title
European journal of clinical pharmacologyauthors
Uno T,Ohkubo T,Sugawara K,Higashiyama A,Motomura S,Ishizaki Tdoi
10.1007/s002280000235subject
Has Abstractpub_date
2000-12-01 00:00:00pages
643-9issue
9-10eissn
0031-6970issn
1432-1041journal_volume
56pub_type
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journal_title:European journal of clinical pharmacology
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journal_title:European journal of clinical pharmacology
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abstract::Nicotine chewing gum (Nicorette 4 mg) and an identical placebo gum were administered on different days, in a double-blind cross over fashion, to 4 men, aged 25-52 years, and 4 women, aged 21-49 years, all healthy non-smokers. The subjects chewed the gum for 30 min and heart rate, blood pressure, electrocardiogram, fin...
journal_title:European journal of clinical pharmacology
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abstract::Jejunal perfusion was performed in 12 healthy volunteers to evaluate the dose dependent effects of loperamide on intestinal absorption, stimulated secretion and transit. In 6 volunteers intestinal perfusion of the jejunal segment with isotonic NaCl solution was followed by addition of loperamide in increasing doses (2...
journal_title:European journal of clinical pharmacology
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abstract::We have studied the pharmacodynamic effects of ramipril, propranolol, and their combination, as well as the effect of propranolol on the pharmacokinetics of ramipril in 12 healthy men (age 24 (SD 6) y, weight 72 (7) kg). Propranolol and placebo, ramipril and placebo, or propranolol and ramipril were given orally for f...
journal_title:European journal of clinical pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
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abstract:OBJECTIVE:To study the influence of CYP3A4 inhibition by ketoconazole on the disposition of venlafaxine in individuals with different CYP2D6 pheno- and genotypes. METHODS:In an open two-phase study, 21 healthy volunteers with known CYP2D6 pheno- and genotype [14 extensive metabolisers (EMs), 7 poor metabolisers (PMs)]...
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journal_title:European journal of clinical pharmacology
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abstract::The metabolic fate and ACTH-suppressant activity of two injectable dexamethasone esters, 21-phosphate and 21-sulphate, were studied in healthy men. After i.v. injection of 20mg free steroid alcohol, dexamethasone phosphate was efficiently hydrolyzed to free dexamethasone, reaching its peak plasma concentration within ...
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abstract::A double blind crossover trial of baclofen against placebo in elderly stroke patients was discontinued because the drug produced an unacceptably high level of drowsiness. In a subsequent study baclofen 10 mg was given orally to 12 elderly stroke patients, and drug concentrations measured from a series of plasma sample...
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