Clin Pharmacokinet
-
Randomized Controlled Trial
Pharmacokinetics and dose proportionality of fentanyl effervescent buccal tablets in healthy volunteers.
Fentanyl effervescent buccal tablets (FEBT) are designed to enhance the rate and efficiency of fentanyl absorption through the buccal mucosa. This study was undertaken to characterise the pharmacokinetics and assess the dose proportionality of FEBT in healthy volunteers within the potential therapeutic dose range. ⋯ The pharmacokinetics of FEBT were characterised by a high early fentanyl concentration as a result of absorption across the buccal mucosa of the oral cavity, which results in bypassing first-pass metabolism. This high early tmax contributed to enhanced early systemic fentanyl exposure. Maximum concentration and AUCinfinity of FEBT increased in a dose-proportional manner from 200 to 810microg. This study provides preliminary pharmacokinetic data for FEBT across the potential therapeutic dose range.
-
Randomized Controlled Trial Multicenter Study Clinical Trial
Effects of application site and subject demographics on the pharmacokinetics of fentanyl HCl patient-controlled transdermal system (PCTS).
The fentanyl HCl patient-controlled transdermal system (PCTS) is a self-contained, preprogrammed, needle-free system currently in development for acute pain management in a medically supervised setting. The objectives of these studies were to evaluate skin application sites for the fentanyl HCl PCTS and to evaluate the effect of patient demographics on its pharmacokinetics. ⋯ Fentanyl HCl is comparably absorbed from the PCTS when it is applied to the upper outer arm or chest. The pharmacokinetics of fentanyl HCl delivered by the PCTS are unaffected by sex, age, race or weight.
-
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.
-
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.
-
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.