Vol.55 No.1 January 2007

Population pharmacokinetics of teicoplanin in infants and children

Masahiro Kobayashi¹⁾, Misayo Arima¹⁾, Toshimi Kimura¹⁾, Masahiro Ishii²⁾, Kazuo Yago¹⁾ and Keisuke Sunakawa³⁾

¹⁾Department of Pharmacy, Kitasato University Hospital,
1-15-1 Kitasato, Sagamihara, Kanagawa, Japan
²⁾Department of Pediatrics, School of Medicine, Kitasato University
³⁾Department of Infectious Disease, School of Medicine, Kitasato University

Abstract

We analyzed teicoplanin (TEIC) pharmacokinetics in infants and children using the nonlinear mixed effects model (NONMEM) to estimate population pharmacokinetics parameters. Subjects were 63 children (28 days to 16 years old) prescribed TEIC at Kitasato University Hospital and undergoing therapeutic drug monitoring. Population pharmacokinetics parameters were calculated using 1-compartment model of clearance (CL_TEIC) and volume of distribution (Vd_TEIC). An exponential error model was used to determine interindividual variability and a relative error model for residual variability. Patient age, gender, weight, serum creatinine, and serum albumin were covariates. The observed TEIC serum concentration was 101 points ranging from 4.4-39.1 μg/mL. TEIC population pharmacokinetics parameters finally estimated were: CL_TEIC=0.00836× (wt/Scr)^0.786 (L/h) and Vd_TEIC=0.81×wt (L). Interindividual variability was CL_TEIC=26.7 (%) and Vd_TEIC=32.7 (%), and residual variability was 2.8 μg/mL. CL_TEIC changes due to aging correlated well with that of kidney gravity. Model validity was sufficient. Our reports suggest that the population parameters are useful in evaluating TEIC pharmacokinetics in children undergoing long-term hospitalization.

Key word

teicoplanin, population pharmacokinetics, NONMEM, child

Received

September 6, 2006

Accepted

November 17, 2006

Jpn. J. Chemother. 55 (1): 17-22, 2007