THE EFFECT OF RENAL IMPAIRMENT ON THE PHARMACOKINETICS OF OXCARBAZEPINE AND ITS METABOLITES

We have studied the effect of renal impairment on the pharmacokinetics of oxcarbazepine, its active monohydroxy-metabolite (which predominat es in plasma), their glucuronides, and the inactive dihydroxy-metaboli te after a single oral dose of oxcarbazepine (300 mg). Six subjects wi th normal renal function and 20 patients with various degrees of renal impairment participated. The mean areas under the plasma concentratio n-time curves of oxcarbazepine and its monohydroxy-metabolite were 2-2 .5-times higher in patients with severe renal impairment (CL(CR) < 10 ml.min(-1)) than in healthy subjects. The apparent elimination half-li fe, of the monohydroxy-metabolite [19 (SD 3) h] in these patients was about twice that in healthy subjects. The effect of renal impairment o n the plasma concentrations of glucuronides was more marked. The renal clearances of the unconjugated monohydroxy-metabolite and its glucuro nides (the main compounds recovered in urine) correlated well with cre atinine clearance. The maximum target dose in patients with slight ren al impairment (CL(CR) > 30 ml.min(-1)) should not be changed. In patie nts with moderate renal impairment (CL(CR) 10-30 ml.min(-1)) it should be reduced by 50%. In patients with severe renal impairment (CL(CR) < 10 ml.min(-1)), the glucuronides of oxcarbazepine and its monohydroxy -metabolite are likely to accumulate during repeated administration, a nd dosage adjustment of oxcarbazepine in these patients could not be p roposed from this single administration study.