Population pharmacokinetics of doxapram in low-birth-weight Japanese infants with apnea.

摘要: This study aimed to determine the population pharmacokinetics of doxapram in low-birth-weight (LBW) infants. A total 92 serum concentration measurements that were obtained from 34 Japanese neonates analyzed using nonlinear mixed-effect modeling (NONMEM). Estimates generated by NONMEM indicated clearance (CL; L/kg/h) was affected postmenstrual age (PMA; weeks), body weight (BW; g), and aspartate aminotransferase (AST; IU/L). In addition, volume distribution (Vd; L/kg) gestational (GA; weeks). The final pharmacokinetic model as follows: CL = BW / PMA × 0.0453 AST−0.373; Vd 2.54 (if GA >28 weeks) 2.11 ≤28 interindividual variabilities 39.9 83.0 %, respectively, residual variability 20.9 %. To clarify reasons for large variations, enzymes involved metabolic pathway also determined. We found metabolized CYP3A4/5.