A model for the determination of carbamazepine clearance in children on mono- and polytherapy. 1998

A L Gray, and J H Botha, and R Miller
Department of Pharmacy, University of Durban-Westville, South Africa. agray@pixie.udw.ac.za

OBJECTIVE To derive a model describing carbamazepine (CBZ) clearance in children, in terms of individual patient characteristics. METHODS One hundred and eighteen steady-state serum carbamazepine concentration measurements were gathered during normal routine care of 72 compliant outpatients (2.3-16.3 years old). Levels were obtained from patients receiving monotherapy (55%), concomitant valproate (26%), or concomitant inducers (phenytoin, phenobarbitone; 19%). A one-compartment model was used to fit the data with the computer programme Nonlinear Mixed Effects Model (NONMEM). RESULTS Weight, age and concomitant medication were all important determinants of clearance. The final model for clearance (1.h-1) was: CL = [0.7(WT) 0.4] . M, where WT is patient weight (kg) and M is a scaling factor for concomitant medication, with a value of 1 for patients on CBZ monotherapy or concomitant valproate and 1.4 for those receiving concomitant inducers. For the purposes of this analysis, bioavailability (f) was assumed to be complete, i.e., f is thus included in the term CL. CONCLUSIONS CBZ clearance decreased with increasing age. As age and weight were correlated, either variable was a satisfactory predictor. The influence of both the inducers and valproate on CBZ clearance was as expected. This model, which describes clearance in terms of patient-specific details, can be used when predicting the maintenance dose required to achieve a target mean steady-state CBZ concentration in children.

UI MeSH Term Description Entries
D008954 Models, Biological Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment. Biological Model,Biological Models,Model, Biological,Models, Biologic,Biologic Model,Biologic Models,Model, Biologic
D002220 Carbamazepine A dibenzazepine that acts as a sodium channel blocker. It is used as an anticonvulsant for the treatment of grand mal and psychomotor or focal SEIZURES. It may also be used in the management of BIPOLAR DISORDER, and has analgesic properties. Amizepine,Carbamazepine Acetate,Carbamazepine Anhydrous,Carbamazepine Dihydrate,Carbamazepine Hydrochloride,Carbamazepine L-Tartrate (4:1),Carbamazepine Phosphate,Carbamazepine Sulfate (2:1),Carbazepin,Epitol,Finlepsin,Neurotol,Tegretol
D002648 Child A person 6 to 12 years of age. An individual 2 to 5 years old is CHILD, PRESCHOOL. Children
D002675 Child, Preschool A child between the ages of 2 and 5. Children, Preschool,Preschool Child,Preschool Children
D004359 Drug Therapy, Combination Therapy with two or more separate preparations given for a combined effect. Combination Chemotherapy,Polychemotherapy,Chemotherapy, Combination,Combination Drug Therapy,Drug Polytherapy,Therapy, Combination Drug,Chemotherapies, Combination,Combination Chemotherapies,Combination Drug Therapies,Drug Polytherapies,Drug Therapies, Combination,Polychemotherapies,Polytherapies, Drug,Polytherapy, Drug,Therapies, Combination Drug
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000293 Adolescent A person 13 to 18 years of age. Adolescence,Youth,Adolescents,Adolescents, Female,Adolescents, Male,Teenagers,Teens,Adolescent, Female,Adolescent, Male,Female Adolescent,Female Adolescents,Male Adolescent,Male Adolescents,Teen,Teenager,Youths

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