Determination of population pharmacokinetic parameters for amikacin in neonates using mixed-effect models

Eur J Clin Pharmacol. 1998 Jan;53(5):337-41. doi: 10.1007/s002280050389.

Abstract

Objective: The population pharmacokinetics of amikacin, in neonates, was investigated using the nonlinear mixed effects model (NONMEM).

Methods: One hundred and six steady-state amikacin serum levels were obtained from 53 black neonates with a mean gestational age of 35.1 weeks and mean age at the start of treatment of 3.1 days. A one-compartment model was used to fit the data.

Results: The final models for clearance (CL) and volume of distribution (V) were: CL(l.h(-1)) = 0.031WT(1.45) x P and V(l) = 0.316WT(1.44) where WT = birth weight (kg) and P = 1.28 for girls and 1.0 for boys. Inclusion of other fixed effect parameters in the model did not significantly improve the fit of the data. The inter-individual variability for CL and V were 18% and 13%. respectively. Intra-individual variability was 29%. Mean (95% CI) values of CL, V and half-life were 0.048 (0.045, 0.051) l.h(-1).kg(-1), 0.434 (0.414, 0.453) l.kg(-1) and 6.4 (6.2, 6.6) h respectively.

Conclusion: Birth weight was an important determinant of both CL and V and, in this data set, gender was also found to influence CL. Mean population pharmacokinetic values were within the range of those previously derived for other neonatal populations using traditional methods.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • African Continental Ancestry Group
  • Amikacin / pharmacokinetics*
  • Anti-Bacterial Agents / pharmacokinetics*
  • Child, Preschool
  • Female
  • Humans
  • Infant
  • Male
  • Metabolic Clearance Rate
  • Models, Statistical
  • Sex Factors

Substances

  • Anti-Bacterial Agents
  • Amikacin