Clinical pharmacology and therapeutics
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Clin. Pharmacol. Ther. · Oct 2004
Randomized Controlled Trial Clinical TrialDifferent dosage regimens of rabeprazole for nocturnal gastric acid inhibition in relation to cytochrome P450 2C19 genotype status.
For the treatment of gastroesophageal reflux disease, intragastric pH should be lower than 4.0 for no more than 4 hours a day (<16.7%). We aimed to develop optimal dosage regimens for rabeprazole to control nocturnal acidity in relation to cytochrome P450 (CYP) 2C19 genotypes. ⋯ We propose that rabeprazole dosage regimens for sufficient acid inhibition are 20 mg once daily for PMs, 20 mg twice daily for heterozygous EMs, and 10 mg 4 times daily for homozygous EMs or heterozygous EMs.
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Clin. Pharmacol. Ther. · Sep 2004
Randomized Controlled Trial Clinical TrialRole of hepatic and intestinal cytochrome P450 3A and 2B6 in the metabolism, disposition, and miotic effects of methadone.
The disposition of the long-acting opioid methadone, used to prevent opiate withdrawal and treat short- and long-lasting pain, is highly variable. Methadone undergoes N -demethylation to the primary metabolite 2-ethyl-1,5-dimethyl-3,3-diphenylpyrrolinium (EDDP), catalyzed in vitro by intestinal, hepatic, and expressed cytochrome P450 (CYP) 3A4. However, the role of CYP3A4 in human methadone disposition in vivo is unclear. This investigation tested the hypothesis that CYP3A induction (or inhibition) would increase (or decrease) methadone metabolism and clearance in humans. ⋯ First-pass intestinal metabolism is a determinant of methadone bioavailability. Intestinal and hepatic CYP3A activity only slightly affects human methadone N -demethylation but has no significant effect on methadone concentrations, clearance, or clinical effects. Greater rifampin effects, compared with troleandomycin and grapefruit juice, on methadone disposition suggest a major role for intestinal transporters and for other CYPs, such as CYP2B6. Interindividual variability and drug interactions affecting intestinal transporter and hepatic CYP3A and CYP2B6 activity may alter methadone disposition.
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Clin. Pharmacol. Ther. · Jun 2004
Randomized Controlled Trial Comparative Study Clinical Trial6'7'-Dihydroxybergamottin contributes to the grapefruit juice effect.
Our objective was to assess the contribution of 6',7'-dihydroxybergamottin (DHB) to the inhibitory effect of grapefruit juice toward intestinal cytochrome P450 (CYP) 3A4. ⋯ The interaction between grapefruit juice serum and felodipine can be attributed largely to DHB. This establishes DHB as an important contributor to the grapefruit juice effect.
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Clin. Pharmacol. Ther. · Jun 2004
Randomized Controlled Trial Comparative Study Clinical TrialEffect of St John's wort dose and preparations on the pharmacokinetics of digoxin.
St John's wort preparations vary in composition, main constituents, formulation, and daily dose administered. The aim of the study was to evaluate the possible pharmacokinetic interaction of marketed St John's wort formulations and doses with digoxin. ⋯ The interaction of St John's wort and digoxin varies within St John's wort preparations and doses and seems to be correlated with the dose, particularly of hyperforin.
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Clin. Pharmacol. Ther. · Apr 2004
Randomized Controlled Trial Comparative Study Clinical TrialFluvoxamine drastically increases concentrations and effects of tizanidine: a potentially hazardous interaction.
Our objective was to study the effect of fluvoxamine on the pharmacokinetics and pharmacodynamics of tizanidine, a centrally acting skeletal muscle relaxant. ⋯ Fluvoxamine seriously affects the pharmacokinetics of tizanidine and increases the intensity and duration of its effects. Inhibition of tizanidine-metabolizing enzyme(s), mainly CYP1A2, by fluvoxamine seems to explain the observed interaction. Because of the potentially hazardous consequences, the concomitant use of tizanidine with fluvoxamine, or other potent inhibitors of CYP1A2, should be avoided.