Disposition of the antiepileptic oxcarbazepine and its metabolites in healthy volunteers.
Oxcarbazepine (oxcarb) 600 and 900 mg (2360 and 3540 mumol) was taken by 3 volunteers (2 female, 1 male; 45-67 kg; age 22-34 years) after an overnight fast. Blood, saliva and urine were collected for the next 72 h for assay of oxcarb, 10,11-dihydro-10-hydroxy-carbamazepine (OHcarb), and 10,11-dihydro-trans-10,11-dihydroxy-carbamazepine (diol). Oxcarb reached a maximum level of about 1 microgram/ml (3.93 mumol/l) within 1 h and dropped below the detection limit (0.1 microgram/ml = 0.39 mumol/l) within 3 h. The active metabolite OHcarb appeared in the blood before oxcarb and reached the higher maximum level of 7.4 microgram/ml (29 mumol/l) after 7 h. Thereafter serum levels decreased with a t1/2 of about 25 h, and after 40 h with a t1/2 of 9 h, the latter agreeing with the renal excretory t1/2 calculated from the urine data (10 h). The ratio of OHcarb concentration in saliva to that in plasma varied considerably (0.3-1.7; median 1; r greater than 0.9), whereas that of blood to plasma was 1.25 with only small variation (r greater than 0.98); OHcarb concentrations in erythrocytes were 50% higher than in plasma. Diol was detected in blood (maximum level 0.5 microgram/ml = 1.84 mumol/l) in 2 volunteers. 45% of the dose could be recovered in urine (Oxcarb 5%, OH-carb 36%, Diol 4%). Whereas Oxcarb was completely conjugated, only 25% of OHcarb was conjugated and diol was unconjugated.
D000328:Adult; D000927:Anticonvulsants / Q000378:metabolism*; D002220:Carbamazepine / Q000031:analogs & derivatives* / Q000378:metabolism; D005260:Female; D006801:Humans; D006900:Hydroxylation; D007700:Kinetics; D008297:Male; D000078330:Oxcarbazepine; D012463:Saliva / Q000378:metabolism; D013997:Time Factors
D000927:Anticonvulsants; D002220:Carbamazepine; D000078330:Oxcarbazepine