British journal of clinical pharmacology
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Br J Clin Pharmacol · Apr 2004
Clinical TrialPopulation pharmacokinetics of raltitrexed in patients with advanced solid tumours.
To investigate the population pharmacokinetics of raltitrexed in patients with advanced solid tumours and to identify patient covariates contributing to the interpatient variability in the pharmacokinetics of raltitrexed. ⋯ A population pharmacokinetic model has been developed for raltitrexed in patients with advanced cancer. Pharmacokinetic parameters of raltitrexed are markedly influenced by the patient's renal function, body weight and serum albumin levels, which may be taken into account in dose individualization. The use of influential covariates to guide anticancer dosage selection may result in less variability in drug exposure and potentially a better clinical outcome.
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Br J Clin Pharmacol · Apr 2004
Multicenter StudyRetrospective population pharmacokinetic analysis of cetirizine in children aged 6 months to 12 years.
To evaluate retrospectively the population pharmacokinetics of cetirizine, a second-generation antihistamine, in children. ⋯ Population analysis predicts a linear increase in cetirizine CL/F and V/F with age, with CL/F being slightly lower in female children, relative to males of the same age. However, this gender difference probably has no clinical consequences. Since V/F increased more rapidly with age than CL/F, a nonlinear increase in half-life was seen, from < 4 h in infants to near the adult value at 12 years of age. The current recommended dosing regimens that younger children should receive lower but more frequent doses, are confirmed by the present analysis.
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Br J Clin Pharmacol · Apr 2004
Randomized Controlled Trial Clinical TrialDifferent inhibitory effect of fluvoxamine on omeprazole metabolism between CYP2C19 genotypes.
Omeprazole is mainly metabolized by the polymorphic cytochrome P450 (CYP) 2C19. The inhibitory effect of fluvoxamine, an inhibitor of CYP2C19 as well as CYP1A2, on the metabolism of omeprazole was compared between different genotypes for CYP2C19. ⋯ Even a low dose of fluvoxamine increased omeprazole exposure in EMs, but did not increase omeprazole exposure in PMs after a single oral dose of omeprazole. These findings confirm a potent inhibitory effect of fluvoxamine on CYP2C19 activity. The bioavailability of omeprazole might, to some extent, be increased through inhibition of P-glycoprotein during fluvoxamine treatment.
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Br J Clin Pharmacol · Apr 2004
Blood-brain barrier transport of morphine in patients with severe brain trauma.
In experimental studies, morphine pharmacokinetics is different in the brain compared with other tissues due to the properties of the blood-brain barrier, including action of efflux pumps. It was hypothesized in this clinical study that active efflux of morphine occurs also in human brain, and that brain injury would alter cerebral morphine pharmacokinetics. ⋯ The unbound AUC ratio below unity in the 'better' human brain tissue demonstrates an active efflux of morphine across the blood-brain barrier. The 'worse' brain tissue shows a decrease in relative recovery for morphine and in some cases also an increase in permeability for morphine over the blood-brain barrier.