Vol.54 No.1 January 2006
Population pharmacokinetics of teicoplanin in adult patients
1)Department of Pharmacy, Fukuroi Municipal Hospital, 2515-1 Kuno, Fukuroi, Shizuoka, Japan
2)Department of Internal Medicine, Fukuroi Municipal Hospital
3)Clinical Pharmacology, Astellas Pharma Inc.
4)Post Marketing Product Development, Astellas Pharma Inc.
Abstract
To establish the appropriate dosage of teicoplanin (TEIC), an antibiotic against methicillin-resistant Staphylococcus aureus (MRSA), we investigated covariates of the interindividual variability in pharmacokinetics using the NONMEM program. The subjects were 120 adult patients who were not on hemodialysis. These patients received TEIC upon admission to our hospital and underwent measurements of their serum TEIC concentrations. We adopted a two-compartment model and assumed an interindividual variability in TEIC clearance (CL), the central volume of distribution (V), and the transfer rate constant, k21, between the two compartments. In our investigation of variation factors, we adopted single or combination models of creatinine clearance (Ccr), serum albumin (Alb), and body weight (wt), which have been found to affect the pharmacokinetics of TEIC. The best-fit model was selected by comparison of the objective functions (OBJ). This model included weight and Ccr or Ccr/Alb as variation factors of CL.
CL=0.00498×Ccr+0.00426×wt (L/h)
CL=0.0117×Ccr/Alb+0.00468×wt (L/h)
Although the OBJ in the model including Ccr/Alb was slightly better than that in the model including Ccr, there was little difference in the precision of the measurement. The interindividual variability of CL in the final models (22%) was less than half of that in base model (46.9%). Given these variation factors, more than half of the interindividual variability of CL can be accounted for. Because the final models are built on broad Ccr patient data, we expect these models to be useful for more accurate dosing programs in clinical situations.
Key word
teicoplanin, population pharmacokinetics, NONMEM, creatinine clearance, MRSA
Received
October 21, 2005
Accepted
December 9, 2005
Jpn. J. Chemother. 54 (1): 1-6, 2006
