Comparison of the pharmacokinetics of lamotrigine in patients with chronic renal failure and healthy volunteers.
OBJECTIVE
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 pharmacokinetics 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 18 ml 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, t1/2,z, CL/F and amount excreted in urine although t1/2,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% CI 1% to 39%) compared with controls and CLR was reduced to 61% (95% CI 46% to 80%) of the control group value. For lamotrigine glucuronide, Cmax was increased 4-fold (95% CI 3.1 to 5.3) and AUC 7.8-fold (95% CI 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% CI 27% to 84%). Concentrations of an N2-methylated cardio-active metabolite, previously observed in dogs, were below the limit of detection (2 ng ml-1) 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.
Wootton
R
R
Department of Clinical Pharmacology, Wellcome Research Laboratories, Beckenham, UK.
Soul-Lawton
J
J
Rolan
P E
PE
Sheung
C T
CT
Cooper
J D
JD
Posner
J
J
D000284:Administration, Oral; D000328:Adult; D000704:Analysis of Variance; D000927:Anticonvulsants / Q000493:pharmacokinetics*; D016903:Drug Monitoring; D005260:Female; D006801:Humans; D007676:Kidney Failure, Chronic / Q000378:metabolism*; D000077213:Lamotrigine; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D014227:Triazines / Q000493:pharmacokinetics*
D000927:Anticonvulsants; D014227:Triazines; D000077213:Lamotrigine