Clinical pharmacology and therapeutics
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Clin. Pharmacol. Ther. · Jan 2004
Randomized Controlled Trial Clinical TrialLanreotide effect on splanchnic blood flow in healthy subjects: effect of the rate of infusion.
Somatostatin is a naturally occurring peptide advocated for the management of hemodynamic complications of chronic liver diseases. The route of administration (bolus application or constant infusion) has been a question of debate. ⋯ On the basis of tolerability and hemodynamic effects, an intravenous infusion of lanreotide seems superior to a bolus injection of the same dose.
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Clin. Pharmacol. Ther. · Dec 2003
Randomized Controlled Trial Clinical TrialRole of P-glycoprotein in the intestinal absorption and clinical effects of morphine.
There is considerable and unexplained individual variability in the morphine dose-effect relationship. The efflux pump P-glycoprotein regulates brain access and intestinal absorption of numerous drugs. Morphine is a P-glycoprotein substrate in vitro, and P-glycoprotein affects morphine brain access and pharmacodynamics in animals. However, the role of P-glycoprotein in human morphine disposition and clinical effects is unknown. This investigation tested the hypothesis that plasma concentrations and clinical effects of oral and intravenous morphine are greater after inhibition of intestinal and brain P-glycoprotein, with the P-glycoprotein inhibitor quinidine used as an in vivo probe. ⋯ Quinidine increased the absorption and plasma concentrations of oral morphine, suggesting that intestinal P-glycoprotein affected the absorption, bioavailability, and, hence, clinical effects of oral morphine. However, quinidine had no effect on morphine concentration-effect relationships, suggesting that if quinidine is an effective inhibitor of brain P-glycoprotein then P-glycoprotein did not appear to have a significant effect on brain access of morphine.
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Clin. Pharmacol. Ther. · Dec 2003
Clinical TrialThe interaction between St John's wort and an oral contraceptive.
The popular herbal remedy St John's wort is an inducer of cytochrome P450 (CYP) 3A enzymes and may reduce the efficacy of oral contraceptives. Therefore we evaluated the effect of St John's wort on the disposition and efficacy of Ortho-Novum 1/35 (Ortho-McNeil Pharmaceutical, Inc, Raritan, NJ), a popular combination oral contraceptive pill containing ethinyl estradiol (INN, ethinylestradiol) and norethindrone (INN, norethisterone). ⋯ St John's wort causes an induction of ethinyl estradiol-norethindrone metabolism consistent with increased CYP3A activity. Women taking oral contraceptive pills should be counseled to expect breakthrough bleeding and should consider adding a barrier method of contraception when consuming St Johns wort.
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Clin. Pharmacol. Ther. · Dec 2003
Implication of cholesterol in cyclosporine pharmacodynamics in minimal change nephrotic syndrome.
High blood cholesterol concentrations in patients with minimal change nephrotic syndrome may affect cyclosporine (INN, ciclosporin) pharmacodynamics and its clinical efficacy, but few attempts have been carried out to disclose this problem. ⋯ The data raised the possibility that hypercholesterolemia in patients with minimal change nephrotic syndrome attenuates cellular and clinical cyclosporine pharmacodynamics. Down-regulation of LDL receptor in T cells was not observed in these patients, and individual deviation of PBMC response to cyclosporine does not appear to be related to the difference of LDL receptor-positive cell numbers.
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Clin. Pharmacol. Ther. · Nov 2003
Comparative Study Clinical Trial Controlled Clinical TrialThe bioavailability of intranasal and smoked methamphetamine.
Patients in harm-reduction treatment programs are switching from intravenous to other routes of methamphetamine (INN, metamfetamine) administration to avoid risks associated with needle use. Relatively little has been reported about the bioavailability of methamphetamine when smoked or used intranasally. ⋯ Intranasal and smoked methamphetamine are well absorbed. Although intranasal or smoked routes may decrease the risk of transmission of blood-borne diseases, exposure to methamphetamine and the possibility of drug-related complications remain substantial.