PHARMACOKINETICS OF LAMOTRIGINE IN PATIENTS WITH RENAL IMPAIRMENT - INFLUENCE OF HEMODIALYSIS

The pharmacokinetics of a single 100 mg oral dose of lamotrigine, a ne w anticonvulsant drug, were studied in six healthy volunteers and in t wenty patients with various degrees of renal impairment. Six of these patients were regularly haemodialysed. Lamotrigine concentrations in p lasma and urine were measured by the HPLC method. The mean peak plasma concentrations of lamotrigine, t(max) volume of distribution and tota l clearance were not significantly modified by the degree of renal imp airment, The elimination half-life of lamotrigine was approximately 25 h in subjects with normal renal function and 50 h in uraemic patients . These are very large variations in uraemic patients and the results were not statistically significant. Renal clearance of lamotrigine is significantly reduced. Urinary elimination of unchanged and conjugated lamotrigine was reduced in uraemic patients. Thus it seems necessary to treat carefully patients with a very severe renal insufficiency sin ce very large variations in pharmacokinetics were found. A 100 mg oral dose every two days is recommended if creatinine clearance is below 1 0 ml/min. Haemodialysis shortened the elimination half-life from 59.6 +/- 28. 1 h during the interdialysis period to 12.2 +/- 6.4 h during t he dialysis period; 17% of the dose was extracted by haemodialysis.