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. Daptomycin was safe and well tolerated. No adverse events related to the infusion were reported. With increased age, there were increases in the area under the plasma concentration-time curve extrapolated to infinity (AUC( infinity )) and the terminal elimination half-life. Systemic (CL) and renal clearance (CL(R)) both decreased with increasing age. The observed changes seen in CL between the two cohorts were most likely a result of changes in renal function, as estimated by creatinine clearance. No statistically significant differences were observed between the two groups in the maximum plasma concentration (C(max)) and volume of distribution at steady state (Vd(ss)). The confidence intervals for the arithmetic mean ratios of the fraction of the dose excreted in the urine as daptomycin (%Fe) (geriatric subjects over younger subjects) were 60% to 101%, indicating that %Fe(dose) was lower in geriatric subjects. These results demonstrate that changes in the pharmacokinetics of daptomycin in the elderly are attributable to changes in renal function, whereas age per se is not a significant factor.