Absorption, distribution, metabolism and excretion of [14C]dexlansoprazole in healthy male subjects.

Background And Objective: The proton pump inhibitor dexlansoprazole is a modified-release formulation of dexlansoprazole, an enantiomer of lansoprazole, which employs a Dual Delayed Release™ (DDR) delivery system. This study was conducted in healthy subjects to assess the absorption, distribution, metabolism and excretion of a 60 mg dose of [14C]dexlansoprazole.

Methods: After multiple daily doses of dexlansoprazole DDR for 4 days followed by a single dose of [14C]dexlansoprazole on day 5, absorption, distribution, metabolism and elimination of [14C]dexlansoprazole were assessed in six healthy male subjects whose CYP (cytochrome P450) 2C19 metabolizer status was also determined.

Effect of hydrochlorothiazide on the pharmacokinetics and pharmacodynamics of febuxostat, a non-purine selective inhibitor of xanthine oxidase.

What Is Already Known About This Subject: Hyperuricaemia and gout frequently coexist with cardiovascular disorders such as hypertension and heart failure. The use of diuretics has been re-established as a first-line treatment for patients with hypertension and the effects of diuretics on serum uric acid may diminish the urate-lowering effects of febuxostat, a novel, potent, non-purine selective inhibitor of xanthine oxidase.

What This Study Adds: Co-administration of febuxostat 80 mg and hydrochlorothiazide 50 mg had no effect on the pharmacokinetics and did not have a clinically significant effect on the pharmacodynamics of febuxostat.

Metabolism and excretion of [14C] febuxostat, a novel nonpurine selective inhibitor of xanthine oxidase, in healthy male subjects.

Absorption, metabolism, and excretion of one 80 mg oral dose of [(14)C] febuxostat ([thiazole-4-(14)C] 2-[3-cyano-4-isobutoxyphenyl]-4-methyl-5-thiazolecarboxylic acid) were studied in 6 healthy subjects. Mean cumulative recovery in excreta was 94% (49% urine and 45% feces) of the dose over 9 days; 87% of the dose was profiled. Seventeen radioactive peaks were observed in urine and fecal chromatograms.

Effect of food or antacid on pharmacokinetics and pharmacodynamics of febuxostat in healthy subjects.

Unlabelled: What is already known about this subject. Febuxostat is a novel nonpurine selective inhibitor of xanthine oxidase. What this study adds.

Pharmacokinetics, pharmacodynamics and safety of febuxostat, a non-purine selective inhibitor of xanthine oxidase, in a dose escalation study in healthy subjects.

Background: Febuxostat is a novel non-purine selective inhibitor of xanthine oxidase currently being developed for the management of hyperuricemia in patients with gout.

Objective: To investigate the pharmacokinetics, pharmacodynamics and safety of febuxostat over a range of oral doses in healthy subjects.

Methods: In a phase I, dose-escalation study, febuxostat was studied in dose groups (10, 20, 30, 40, 50, 70, 90, 120, 160, 180 and 240 mg) of 12 subjects each (10 febuxostat plus 2 placebo).

The effect of hepatic insufficiency on the safety and pharmacokinetics of paricalcitol (Zemplar).

Background/aims: Paricalcitol is highly protein bound, extensively metabolized and eliminated primarily by hepatobiliary excretion. This study was designed to determine if hepatic disease alters the pharmacokinetics or affects the safety of paricalcitol.

Methods: Subjects with mild (n = 5) or moderate (n = 5) hepatic impairment, and subjects with normal hepatic function (n = 10) enrolled in and completed the study.

The effect of mild and moderate hepatic impairment on pharmacokinetics, pharmacodynamics, and safety of febuxostat, a novel nonpurine selective inhibitor of xanthine oxidase.

To assess the effect of hepatic impairment on the pharmacokinetics, pharmacodynamics, and safety of febuxostat at steady state, multiple once-daily 80-mg oral doses of febuxostat were administered to subjects with normal hepatic function and to subjects with mild or moderate hepatic impairment. There were no statistically significant differences in the plasma pharmacokinetic parameters for unbound febuxostat and its active metabolites between subjects with mild or moderate hepatic impairment and those with normal hepatic function. The percentage decrease in serum uric acid appeared to be lower in hepatic impairment groups (49% [mild] and 48% [moderate]) as compared to the normal hepatic group (62%).

Metabolism and disposition of the HIV-1 protease inhibitor lopinavir (ABT-378) given in combination with ritonavir in rats, dogs, and humans.

Purpose: The objective of this study was to examine the metabolism and disposition of the HIV protease inhibitor lopinavir in humans and animal models.

Methods: The plasma protein binding of [14C]lopinavir was examined in vitro via equilibrium dialysis technique. The tissue distribution of radioactivity was examined in rats dosed with [14C]lopinavir in combination with ritonavir.