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Comparison of the pharmacokinetics of lamotrigine in patients with chronic renal failure and healthy volunteers
Author(s) -
Wootton R.,
SoulLawton J.,
Rolan P. E.,
Sheung C. T. C. Fook,
Cooper J. D. H.,
Posner J.
Publication year - 1997
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/j.1365-2125.1997.tb00133.x
Subject(s) - lamotrigine , pharmacokinetics , metabolite , medicine , creatinine , urine , chronic renal failure , renal function , active metabolite , pharmacology , urology , gastroenterology , epilepsy , psychiatry
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 N 2 ‐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 C max , t max , 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, V z /F was 18% higher (95% Cl 1% to 39%) compared with controls and CL R was reduced to 61% (95% Cl 46% to 80%) of the control group value. For lamotrigine glucuronide, C max , 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. CL R was approximately 9‐fold lower and apparent t 1 / 2 was increased by 53% (95% Cl 27% to 84%). Concentrations of an N 2 ‐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.