Population pharmacokinetic modeling of steady state carbamazepine clearance in children, adolescents, and adults

Carbamazepine (CBZ) clearance decreases from childhood to adulthood and the factors determining this change could include age, size, autoinduction, or maturational changes. This study ainu to describe the population pharmacok inetics of CBZ in children and young adults and rest the hypothesis that CB Z clearance correlates with weight, surface area, and age. CBZ therapeutic drug monitoring data (sparse data) were collected from child and adult epil eptics, and rich data were obtained from a bioequivalence study of CBZ in y oung adults. Population pharmacokinetic analysis was performed using NONMEM V. Forward stepwise, multiple regression was performed on the covariates. Bootstrap validation was performed. A total of 946 observations from 91 sub jects, ages 0.7-37 years, were collected and analyzed. A one-compartment, f irst-order absorption and elimination model, with exponential interindividu al error and additive residual error models was developed. The population m odel was: Clearance (Lhr(-1)) = ((2.24(.)Surface area (m(2))) + (0.047(.)Do se (mg(.)kg(-1))); Volume of distribution (L) = 0.37(.)weight (kg); Absorpt ion rate constant = 0.013 (hr(-1)). CBZ clearance increased with surface ar ea and dose.