A model for the determination of carbamazepine clearance in children on mono- and polytherapy |
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Authors: | A L Gray J H Botha R Miller |
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Institution: | (1) Department of Pharmacy, University of Durban-Westville, Private Bag X54001, Durban 4000, South Africa Tel.: +27 31 2044358; Fax: +27 31 2044792 e-mail: agray@pixie.udw.ac.za, ZA;(2) Department of Clinical and Experimental Pharmacology, University of Natal, South Africa, ZA;(3) Drug Studies Unit, Department of Pharmacology, University of Durban-Westville, South Africa, ZA |
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Abstract: | 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 out-patients (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 (l · 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.
Received: 10 May 1997 / Accepted: 16 February 1998 |
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Keywords: | Carbamazepine Population pharmacokinetics Children NONMEM |
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