Changes in vancomycin pharmacokinetics during treatment.

Using data gathered in routine monitoring, the pharmacokinetics of vancomycin during the first 10 days of treatment were compared with the pharmacokinetics after 10 days of treatment in 46 adult patients with normal renal function, ages 17-85 years old (mean +/- SD: 50.8 +/- 17.5). The mean time from initiation of treatment to the first sample determination was 5.5 days, and the mean time to the second determination was 13.4 days. Statistical differences between the two periods were observed for all pharmacokinetic parameters, except for the steady-state distribution volume. After 10 days of treatment, the mean +/- SD of the vancomycin clearance and elimination rate constant decreased from 1.31 +/- 0.82 to 1.13 +/- 0.72 ml/kg/min (p = 0.0044) and from 0.13 +/- 0.08 to 0.10 +/- 0.06 h-1 (p = 0.091), respectively. The half-life (t1/2) increased from 8.01 +/- 6.82 to 10.02 +/- 8.00 h (p = 0.012). The median percentage of the increment of t1/2 was 9.4%. The increase in t1/2 was > 50% in 12 patients and > 100% in nine cases. No association was found between the increment of t1/2 and the cumulative vancomycin dose. Frequent monitoring of serum vancomycin seems indicated, given the risk of decreased elimination during prolonged treatment.