A study of the pharmacokinetic interaction of istradefylline, a novel therapeutic for Parkinson's disease, and atorvastatin.

The effect of steady-state istradefylline, an agent for Parkinson's disease with P-glycoprotein and CYP3A inhibitory activity, on the pharmacokinetics of atorvastatin and its metabolites was evaluated in healthy volunteers. A single 40-mg dose of atorvastatin was administered to 20 subjects. After a 4-day washout, subjects received a single 40-mg atorvastatin dose following 40 mg istradefylline (n=16) or placebo (n=4) daily for 14 days.

The pharmacokinetics of daptomycin in moderately obese, morbidly obese, and matched nonobese subjects.

Daptomycin pharmacokinetics were studied in adult volunteers who were moderately obese (body mass index [BMI] = 25-39.9 kg/m2) or morbidly obese (BMI > or =40 kg/m2) and a matched (gender, age, renal function) nonobese (BMI between 18.5 and 24.

Population pharmacokinetics of daptomycin.

Data from subjects in nine phase 1 (n = 153) and six phase 2/3 (n = 129) clinical trials were combined to identify factors contributing to interindividual variability in daptomycin pharmacokinetics (PK). Over 30 covariates were considered. A two-compartment model with first-order elimination provided the best fit for data on daptomycin concentrations in plasma over time.

Moderate liver impairment has no influence on daptomycin pharmacokinetics.

Daptomycin (N-decanoyl-L-tryptophyl-L-asparaginyl-L-aspartyl-L-threonylglycyl-L-ornithyl-L-aspartyl-D-alanyl-L-aspartylglycyl-D-seryl-threo-3-methyl-L-glutamyl-3-anthraniloyl-L-alanine-lactone) is a novel cyclic lipopeptide antibiotic derived from the fermentation of Streptomyces roseosporus. Daptomycin was recently approved for the treatment of complicated skin and skin structure infections caused by aerobic gram-positive bacteria, including those caused by methicillin-resistant and methicillin-susceptible Staphylococcus aureus. This single-dose, parallel-design, matched-controlled study was designed to evaluate the pharmacokinetics of daptomycin in subjects between ages 18 and 80 years with moderately impaired hepatic function (Child-Pugh Class B, n = 10).

Single-dose pharmacokinetics of daptomycin in young and geriatric volunteers.

Daptomycin is a novel lipoprotein antibiotic that was recently approved for the treatment of complicated skin and skin structure infections caused by aerobic gram-positive bacteria. The pharmacokinetics of daptomycin was evaluated after a single 0.5-hour intravenous infusion of 4 mg/kg to groups of young adult (18-30 years) and geriatric (>or= 75 years) volunteers.