The pharmacokinetics of thiopental in pediatric surgical patients

Abstract

Thiopental pharmacokinetics and protein binding were determined in 24 pediatric surgical patients with normal hepatic and renal function, ranging in age from 5 months to 13 yr. These pharmacokinetic data were compared with those from 11 adult patients previously studied at our institution. All pediatric patients received a single intravenous bolus of thiopental, 4.0 ± 0.08 mg.kg-1 (mean ± SD), while the adult patients received 6.0 ± 0.74 mg.kg-1. Distribution phase kinetics and volume of distribution at steady state (Vd(ss) did not differ statistically between the two groups. The degree of serum protein binding of thiopental also was similar in pediatric and adult patients with free fractions of 13.2% ± 1.5% and 13.6% ± 1.3%, respectively. The two patient groups showed a marked difference in elimination half-time and clearance of thiopental. Total drug clearance was 6.6 ± 2.2 ml.kg-1.min-1 for pediatric patients and 3.1 ± 0.5 ml.kg-1.min-1 for adults (P<0.001). The elimination half-time of 6.1 ± 3.3 hours found in pediatric patients was significantly shorter (P<0.005) than that for adults, 12 ± 6 hours. Linear regression of the pediatric data failed to achieve significance (P=0.06) for elimination half-time to increase with age, while clearance decreased (P<0.001) with increasing age. The shorter elimination half-time seen in infants and children was due solely to greater hepatic clearance. Thus, recovery time after large or repeated doses may be more for infants and children than for adults because of the higher clearance.