Comparison of the pharmacokinetics of lamotrigine in patients with chronic renal failure and healthy volunteers

Abstract

Aims The aim of this study was to compare the pharmacokinetics of the anti‐epileptic agent, lamotrigine, in patients with chronic renal failure and healthy volunteers. Methods Non‐compartmental pharmacoknetics of a single oral dose (200 mg) of the anti‐epileptic agent, lamotrigine, and its main metabolite, lamotrigine N2‐glucuronide, were determined for 10 patients with chronic renal failure of mean estimated creatinine clearance 18ml min−1 and a control group of 11 healthy volunteers, matched for age and gender. Results For lamotrigine, there were no significant differences in Cmax, tmax, AUC, t 1/2, z, CL/F and amount excreted in urine although t 1/2, z, tended to be longer for the renal failure group with a mean (± s.d.) of 35.9 ± 10.7 h vs 27.8 ± 4.3 h for the control group. For the renal failure group, Vz/F was 18% higher (95% Cl 1% to 39%) compared with controls and CLR was reduced to 61% (95% Cl 46% to 80%) of the control group value. For lamotrigine glucuronide, Cmax, was increased 4‐fold (95% Cl 3.1 to 5.3) and AUC 7.8–fold (95% Cl 6.0 to 10.1) in the renal failure group compared with controls. CLR was approximately 9‐fold lower and apparent t1/2 was increased by 53% (95% Cl 27% to 84%). Concentrations of an N2 ‐methylated cardo‐active metabolite, previously observed in dogs, were below the limit of detection (2 ng ml−7) of the ASTED/h.p.l.c. assay in the renal failure group as well as controls. Conclusions These results indicate that impaired renal function will have little effect on the plasma concentrations of lamotrigine achieved for a given dosing regimen.