Pharmacokinetics of rifampin in children. I. Multiple dose intravenous infusion.

The pharmacokinetics of intravenous rifampin (280 +/- 78 mg/m2) were investigated during multiple dose administration in 12 pediatric patients aged 3 months to 12.8 years. Serum rifampin concentration data were fit to a linear one-compartment model. There was a significant effect of duration of therapy on rifampin clearance (Cl) and half-life (t1/2) (p = 0.027 and p = 0.048, respectively). A mean increase of 52.0% in Cl (3.10-4.72 L/h/m2) and a mean decrease of 27.0% in t1/2 (2.38-1.73 h) were observed when data collected during the first 2 days of therapy were compared with data collected following 8 or more days of therapy. Peak concentrations extrapolated to the end of infusion were 27.0 +/- 8.2 micrograms/ml, and concentrations at 8 h after the dose were only 1.9 +/- 1.5 micrograms/ml. There was no significant effect of duration of therapy on these concentration values. There was no correlation between Cl and age or administered dose. Intrapatient variation in Cl was great, as evidence by the lack of correlation of initial Cl values with subsequent values in individual patients (r = 0.259). It would appear that dosage intervals may need to be shortened from 12 to 8 h during continuous therapy, and that periodic measurement of rifampin concentration may be required.