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Pharmacokinetics of rifampin in children. I. Multiple dose intravenous infusion
Insights
Pediatric patients receiving intravenous rifampin showed significant changes in drug clearance and half-life over time. Dosage intervals may require adjustment and monitoring during extended therapy.
Area of Science:
- Pharmacokinetics
- Pediatric Pharmacology
Background:
- Rifampin is a crucial antibiotic for treating various infections.
- Understanding its pharmacokinetic profile in pediatric populations is essential for effective treatment.
Purpose of the Study:
- To investigate the pharmacokinetics of intravenous rifampin in pediatric patients.
- To assess the impact of therapy duration on rifampin clearance and half-life.
Main Methods:
- A linear one-compartment model was used to analyze serum rifampin concentration data.
- Data from 12 pediatric patients (3 months to 12.8 years) were collected over multiple doses.
Main Results:
- Rifampin clearance significantly increased by 52.0% and half-life decreased by 27.0% from early to later stages of therapy.
- No significant correlation was found between clearance and patient age or administered dose.
- High intrapatient variability in clearance was observed.
Conclusions:
- Therapy duration significantly impacts rifampin pharmacokinetics in children.
- Shortening dosage intervals to 8 hours and periodic drug concentration monitoring may be necessary during prolonged treatment.
Abstract:
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.