Clinical pharmacology and therapeutics
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Clin. Pharmacol. Ther. · Nov 2004
Comment Letter Case ReportsDrug interaction of tizanidine and fluvoxamine.
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Clin. Pharmacol. Ther. · Nov 2004
Randomized Controlled Trial Comparative Study Clinical TrialIntravenous and oral alfentanil as in vivo probes for hepatic and first-pass cytochrome P450 3A activity: noninvasive assessment by use of pupillary miosis.
Systemic clearance of intravenous (IV) alfentanil (ALF) is an in vivo probe for hepatic cytochrome P450 (CYP) 3A activity, miosis is a surrogate for plasma ALF concentrations, and IV ALF miosis is a noninvasive probe for hepatic CYP3A. This investigation characterized the bioavailability and first-pass metabolism of oral ALF and tested the hypotheses that (1) first-pass ALF clearance reflects first-pass CYP3A activity, (2) miosis after oral ALF will reflect intestinal and hepatic CYP3A activity, and (3) miosis can approximate plasma concentration-based pharmacokinetic measures for IV and oral ALF as a noninvasive in vivo probe for hepatic and first-pass CYP3A activity and drug interactions. Results were compared with those for midazolam (MDZ), an alternative CYP3A probe. ⋯ ALF and MDZ have similar intestinal extraction but low and intermediate hepatic extraction, respectively. Systemic and oral clearances of ALF are excellent in vivo probes for hepatic and first-pass CYP3A activities and drug interactions. Miosis was an acceptable surrogate for plasma ALF. ALF miosis may be a suitable noninvasive in vivo probe for both hepatic and first-pass CYP3A.
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Clin. Pharmacol. Ther. · Oct 2004
Randomized Controlled Trial Clinical TrialAngiotensin-converting enzyme inhibition and smoking potentiate the kinin response to cardiopulmonary bypass.
This study tested the hypothesis that angiotensin-converting enzyme (ACE) inhibitors potentiate activation of the kallikrein-kinin system during cardiopulmonary bypass (CPB). ⋯ Preoperative ACE inhibitors and smoking potentiate the kinin response to CPB and may contribute to the hemodynamic and fibrinolytic response observed during CPB.
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Clin. Pharmacol. Ther. · Oct 2004
Clinical Trial Controlled Clinical TrialEffect of St John's wort on imatinib mesylate pharmacokinetics.
Imatinib is a potent inhibitor of the Bcr-Abl and c- kit tyrosine kinases and is approved for the treatment of Philadelphia chromosome-positive chronic myelogenous leukemia and gastrointestinal stromal tumors. Because imatinib is predominantly metabolized by cytochrome P450 (CYP) 3A4, its pharmacokinetics may be altered when it is coadministered with drugs or herbs (eg, St John's wort) that modulate CYP3A4 activity. Thus we examined the effects of St John's wort on imatinib pharmacokinetics. ⋯ These data indicate that St John's wort increases imatinib clearance. Thus patients taking imatinib should avoid taking St John's wort. Concomitant use of enzyme inducers, including St John's wort, may necessitate an increase in the imatinib dose to maintain clinical effectiveness.
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Clin. Pharmacol. Ther. · Oct 2004
Clinical TrialQT interval prolongation after oxytocin bolus during surgical induced abortion.
Although oxytocin, a uterotonic agent, may cause short-term vasodilation that results in severe hypotension, it is still routinely given as an intravenous bolus injection during surgical suction curettage. Two reported cases of ventricular tachycardia after oxytocin bolus in patients with long QT interval syndrome led us to assess the effect of oxytocin on QT interval. ⋯ Oxytocin intravenous bolus induced a large and transient QTc interval prolongation, suggesting that it may lead to proarrhythmia in circumstances favoring QTc interval increase.