Abstract
In order to clarify vancomycin pharmacokinetics in a Japanese elderly population, vancomycin (10 mg/kg) was repeatedly administered to 6 elderly female patients with methicillin-resistant Staphylococcus aureus (MRSA) infections (age 78 .3±5.9 years, weight 34.8±9.4 kg, CLCR 41.9±19.8 ml/min, mean±SD) by 1-hour constant infusion for 6days. Vancomycin was given to elderly patients once on day l and 6, and twice on day 2 to day 5 at 12-hour.intervals. Six healthy male volunteers (age 22 .0±1.7 years, weight 62.7±7.5kg, CLCR 115.0±9.6 ml/min, mean±SD) were administered vancomvcin once by 1-hour infusion. Serum and urinary vancomycin concentrations were measured by fluorescence polarization immunoassay and bioassay, respectively . Total clearance (CL) of vancomycin was 95.50±15.74 ml/min in the healthy control group subjects, while the value of CL was 35.21±13.29 ml/min in the elderly patients on 1st day. In elderly patients, vancomycin was substantially eliminated extrarenally in comparison with the healthy subjects. Pharmacokinetic parameters were compared between day 1 and day 6 in the elderly patients. Nonlinear pharmacokinetics was observed during multiple administration, t1/2 was prolonged from 12.99±7.11 to 21.95±12.00 hour on day 6 (p<0 .05). CL significantly decreased from 35.21±13.29 to 23.64±8 .50 ml/min on day 6 (p<0.05).In contrast, renal clearance of vancomycin (CLR) remained constant throughout the study (15.06±5.86 and 17.76±7.78 ml/min on day 1 and day 6, respectively). The ratio of non renal clearance (CLNR) to CL was decreased from 0.568 (mean) to 0.268 after multiple dosing of vancomycin. The results suggested that vancomycin was eliminated mainly extrarenally in the elderly patients and that this extrarenal elimination was reduced during the repeated administration. These findings may have clinical implications for the long-term treatment of elderly patients with MRSA infections .
