The effect of body size on the metabolic clearance of carbamazepine

Objectives. To examine the profile of the known pathways of carbamazepine ( CBZ) metabolism in a group of children and adolescents, and to test for ass ociations with physical measurements, age and plasma hormonal levels. Study design. Cross-sectional study of children and adolescents attending a neurological outpatients department who were medicated with CBZ. Partial c learances of CBZ to CBZ-epoxide (CBZ-ep), CBZ-10,11-trans-diol (CBZ-diol), 2-hydroxy-CBZ (CBZ-2-OH), 3-hydroxy-CBZ (CBZ3-OH), CBZ-acridan (CBZ-acr) an d their respective glucuronides were calculated by relating 24-h recovery o f these metabolites from urine to trough steady-state serum CBZ levels. CBZ and its metabolites were measured by a gradient high performance liquid ch romatography (HPLC) method. Serum CBZ-ep, LH, FSK, prolactin, IGF-I, and te stosterone or oestradiol and progesterone were also measured. Surface area (SA) and liver volume (LV) were calculated from height and weight. Results. Twelve males and nine females with an age range of 6-17 years part icipated in the study. Partial clearance to each of the metabolites was mos t strongly correlated with the calculated size of the liver relative to bod y weight. These associations persisted when corrected for potential confoun ders using multiple regression analysis. Conclusion. In the age group studied, urinary clearance of CBZ to its known metabolites is proportional to the size of the liver relative to body weig ht. Copyright (C) 2000 John Wiley & Sons, Ltd.