Clin Pharmacokinet
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Randomized Controlled Trial Clinical Trial
Population pharmacokinetics of delavirdine and N-delavirdine in HIV-infected individuals.
Delavirdine is a non-nucleoside reverse transcriptase inhibitor used in combination regimens for the treatment of HIV-1 infection. Our objective was to characterise the population pharmacokinetics of delavirdine in HIV-infected patients who participated in the adult AIDS Clinical Trials Group (ACTG) 260 and 261 studies. ⋯ Delavirdine disposition exhibits nonlinear pharmacokinetics and large interpatient variability, and is significantly altered by time of day (impacting potential therapeutic drug monitoring and future pharmacokinetic study designs). Although race and sex appear to influence delavirdine pharmacokinetics, men and women and patients of different races should receive similar mg/kg dosage regimens. The presence of large interpatient variability supports the further investigation of the utility of therapeutic drug monitoring for delavirdine, if target drug concentrations can be better defined.
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Randomized Controlled Trial
Effects of enteral feeding on the oral bioavailability of moxifloxacin in healthy volunteers.
Moxifloxacin is a new generation fluoroquinolone antimicrobial agent used worldwide. In clinical practice in intensive care units, moxifloxacin may be frequently administered through a nasogastric feeding tube. In the absence of an oral liquid formulation and since the multivalent cations contained in enteral feeds may potentially impair absorption of moxifloxacin administered via this route, we studied the effect of concomitant enteral feeding on the pharmacokinetics and tolerability of moxifloxacin administered as a crushed tablet through the nasogastric tube. ⋯ There was no clinically relevant effect of enteral feeding on the pharmacokinetics of oral moxifloxacin in healthy volunteers. This result has to be evaluated in patients, particularly those from the intensive care unit, who are characterised by severe infectious and/or concomitant diseases that might influence absorption of moxifloxacin.
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Randomized Controlled Trial Comparative Study Clinical Trial
Characterisation of the pharmacokinetics of the fentanyl HCl patient-controlled transdermal system (PCTS): effect of current magnitude and multiple-day dosing and comparison with IV fentanyl administration.
The fentanyl HCl patient-controlled transdermal system (PCTS) is a self-contained, preprogrammed, noninvasive analgesic delivery system for acute pain management. We carried out three studies with the following objectives: study I to evaluate the relationship between fentanyl absorption and the magnitude of current applied to the system; study II to determine dose-proportionality for the fentanyl HCl PCTS (25 and 40 microg); and study III to describe the effects of single- and multiple-day administration on the pharmacokinetics of fentanyl delivered by the PCTS. ⋯ A linear relationship exists between the amount of current applied to the fentanyl HCl PCTS and the amount of fentanyl absorbed. There is dose-proportionality in the pharmacokinetics of the fentanyl HCl PCTS 25 and 40 microg. Multiple-day administration does not affect the pharmacokinetics of the fentanyl HCl PCTS 40 microg. The system was well tolerated, even after repeated application.
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Randomized Controlled Trial Clinical Trial
Contribution of cytochrome P450 2D6 to 3,4-methylenedioxymethamphetamine disposition in humans: use of paroxetine as a metabolic inhibitor probe.
3,4-Methylenedioxymethamphetamine (MDMA) is a synthetic amphetamine derivative typically used for recreational purposes. The participation of cytochrome P450 (CYP) 2D6 in the oxidative metabolism of MDMA may suggest an increased risk of acute toxicity in CYP2D6 poor metabolisers. This study was aimed at assessing the contribution of CYP2D6 to MDMA disposition in vivo using paroxetine as a metabolic probe inhibitor. Paroxetine, a CYP2D6 inhibitor, was repeatedly administered before MDMA administration. ⋯ The contribution of CYP2D6 to MDMA metabolism in humans is not >30%, therefore other CYP isoenzymes may contribute to O-demethylenation of MDMA. Accordingly, the relevance of genetic polymorphism in CYP2D6 activity on MDMA effects and MDMA-induced acute toxicity should be examined as well as the interactions of other CYP2D6 substrates with MDMA, once the enzyme is inhibited. The pharmacokinetics of HM-paroxetine in humans after the administration of repeated doses is reported for the first time in this study.
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Randomized Controlled Trial Clinical Trial
Pharmacokinetic drug interactions of gefitinib with rifampicin, itraconazole and metoprolol.
Gefitinib (IRESSA, ZD1839), an epidermal growth factor receptor tyrosine kinase inhibitor, has been approved in several countries for the treatment of advanced non-small-cell lung cancer. Preclinical studies were conducted to determine the cytochrome P450 (CYP) isoenzymes involved in the metabolism of gefitinib and to evaluate the potential of gefitinib to cause drug interactions through inhibition of CYP isoenzymes. Based on these findings, three clinical studies were carried out to investigate pharmacokinetic drug interactions in vivo with gefitinib. ⋯ Although CYP3A4 inducers may reduce exposure to gefitinib, further work is required to define any resultant effect on the efficacy of gefitinib. Exposure to gefitinib is increased by coadministration with CYP3A4 inhibitors, but since gefitinib is known to have a good tolerability profile, a dosage reduction is not recommended. Gefitinib is unlikely to exert a clinically relevant effect on the pharmacokinetics of drugs that are dependent on CYP2D6-mediated metabolism for their clearance, but the potential to increase plasma concentrations should be considered if gefitinib is coadministered with CYP2D6 substrates that have a narrow therapeutic index or are individually dose titrated.