PLASMA AND TONSILLAR TISSUE PHARMACOKINETICS OF TEICOPLANIN FOLLOWINGINTRAMUSCULAR ADMINISTRATION TO CHILDREN

The population pharmacokinetics of teicoplanin in plasma and tonsillar tissue in children was determined following intramuscular administrat ion. Thirty seven patients in all received either a single 5 mg/kg dos e; 2 doses of 5 mg/kg, 12 h apart; 3 doses of 5 mg/kg, 12 h apart; or, a single 10 mg/kg dose. Limited data, comprising a maximum of 2 blood samples and 1 tonsillar sample were taken from each patient, with the maximum time being 48 h after the first dose of teicoplanin (in the 3 X5 mg/kg dosing schedule). All plasma data were analyzed simultaneousl y by a maximum likelihood method employing a modified EM algorithm. A first-order absorption, one-compartment disposition model was fitted t o the data. Mean parameter values (with lower and upper 95% confidence intervals) were: clearance/bioavailability, 0.024 L h(-1) kg(-1) (0.0 20-0.027); volume of distribution/bioavailability, 0.61 L kg(-1) (0.54 -0.70); absorption rate constant, 0.43 h(-1) (0.31-0.61). A first-orde r transfer model for distribution of teicoplanin between plasma and to nsillar tissue was fitted to the tonsil data. The mean parameter value s (95% confidence intervals) were: transfer rate constant between plas ma and tonsils 0.49 h(-1) (0.35-0.67); transfer rate constant between tonsils and plasma 0.73 h(-1) (0.52-1.03). These rate constants corres pond to a distribution half-life of 0.95 h and an equilibrium distribu tion concentration ratio between tonsillar tissue and plasma of 0.67. After normalising clearance and volume of distribution for body weight , there was no further influence of body weight on the pharmacokinetic parameters. Also, there was no effect of dose, and as two formulation s were used, one for the 5 mg/kg dose and the other for the 10 mg/kg d ose, no effect of formulation on the pharmacokinetics of teicoplanin a fter im (intramuscular) administration was found. (C) 1998 Elsevier Sc ience B.V. All rights reserved.