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 associations 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 clearances of CBZ to CBZ-epoxide (CBZ-ep), CBZ-10,11-trans-diol (CBZ-diol), 2-hydroxy-CBZ (CBZ-2-OH), 3-hydroxy-CBZ (CBZ-3-OH), CBZ-acridan (CBZ-acr) and their respective glucuronides were calculated by relating 24-h recovery of these metabolites from urine to trough steady-state serum CBZ levels. CBZ and its metabolites were measured by a gradient high performance liquid chromatography (HPLC) method. Serum CBZ-ep, LH, FSH, prolactin, IGF-I, and testosterone 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 participated in the study. Partial clearance to each of the metabolites was most strongly correlated with the calculated size of the liver relative to body weight. These associations persisted when corrected for potential confounders 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 weight.