Vancomycin disposition: the importance of age

We examined the influence of age on vancomycin kinetics in 12 normal healthy men (six young and six elderly) after an intravenous infusion of 6 mg/kg. Serial blood and urine samples were collected for up to 2 days after dosing and were assayed for unchanged drug by a specific radioimmunoassay. Serum concentrations of vancomycin after infusion declined in a multiphasic manner. Both serum and urinary excretion data were simultaneously fit by a three-compartment model with SAAM-27 computer programs. Estimates of mean t1/2 obtained from the terminal phase of the drug disposition profile showed the t1/2 to be longer in the elderly than in the young subjects (12.1 and 7.2 hr). Although there was no change in the initial distribution volume of the central compartment, total systemic and renal clearances were reduced in the elderly and did not correlate with renal function. The increase in the vancomycin volume of distribution at steady state was ascribed to enhanced tissue binding of drug in the elderly, since the mean fraction of vancomycin bound in systemic pool of the young and elderly did not differ (0.53 and 0.56). In-depth analysis of excretion data tends to support suggestions of vancomycin excretion solely by glomerular filtration. Our data strongly suggest the need for adjustment or modification of recommended vancomycin dosing schedules in the elderly.