Journal of Pharmacokinelics and Biopharmaceutics, Vol. 25, No. 6, 1997 695 0090-4«6X/97/l200-0«S$l2.50/0 © 1997 Plenum Publishing Corporation Implementation and Evaluation of a Stochastic Control Strategy for Individualizing Teicoplanin Dosage Regimen Michel Tod, 1,2,4 Patrice Alet, 1 Olivier Lortholary,2,3 and Olivier Petitjean1' 2 Received August 30, 1996—Final December 10, 1997 A stochastic control strategy for individualizing teicoplanin dosing schedule in neutropenic patients is proposed and compared to the usual Bayesian approach based on the mode of the posterior density of the model perameters. Teicoplanin disposition is described by a bicompurlmental model. Age, body weight, serum creatinine, white blood cell count, and sex can be included as covariates. Posterior density of model parameters is obtained by Bayes theorem under a discrete form from which the posterior density of leicoplanin trough concentrations are computed for any dosing schedule. Optimal maintenance dose is determined by minimizing the cost associated, through a logarithmic risk function, to the concentrations being outside the therapeutic range. In Monte Carlo simulation studies on 300 individuals, stochastic control was more accurate than, and equally precise as the usual Bayesian approach. Two-sample based predictions were not better than one- sample based ones. Inclusion of covariates in the model improved dramatically the performances of both strategies. A small retrospective study based on real data (n = 16 patients) shows that reasonable accuracy (bias of 0.7 mg/L) and precision (img/L) in teicoplanin trough concentra- tion prediction is obtained with both strategies provided that covariates are taken into account. KEY WORDS: therapeutic drug monitoring; stochastic control; teicoplanin. INTRODUCTION Teicoplanin is a glycopeptide antibiotic used for treating severe Gram- positive infections by intramuscular or intravenous route (1). In particular, teicoplanin is given in combination with pMactams and aminoglycosides as an empirical antibiotic regimen in febrile neutropenic patients (2). The pharmacokinetics of teicoplanin in neutropenic patients have been shown 'Departement de Pharmacotoxicologie, Hopital Avicenne, 125 Route de Stalingrad, Bobigny 93009, France. 'Centre de Recherche en Pathologic Infectieuse et Tropicale, Faculte de Medecine Paris-Nord, Bobigny 93000, France. 'Service de Medecine Interne, Hopital Avicenne, Bobigny 93009, France. *To whom correspondence should be addressed.