Pharmacokinetics of lamotrigine in patients with renal impairment: influence of haemodialysis.
The pharmacokinetics of a single 100 mg oral dose of lamotrigine, a new anticonvulsant drug, were studied in six healthy volunteers and in twenty patients with various degrees of renal impairment. Six of these patients were regularly haemodialysed. Lamotrigine concentrations in plasma and urine were measured by the HPLC method. The mean peak plasma concentrations of lamotrigine, tmax, volume of distribution and total clearance were not significantly modified by the degree of renal impairment. 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 since very large variations in pharmacokinetics were found. A 100 mg oral dose every two days is recommended if creatinine clearance is below 10 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 the dialysis period; 17% of the dose was extracted by haemodialysis.
Fillastre
J P
JP
Department of Nephrology, University of Rouen, France.
Taburet
A M
AM
Fialaire
A
A
Etienne
I
I
Bidault
R
R
Singlas
E
E
D000328:Adult; D000368:Aged; D000927:Anticonvulsants / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D002851:Chromatography, High Pressure Liquid; D005260:Female; D005965:Glucuronates / Q000097:blood / Q000652:urine; D006207:Half-Life; D006801:Humans; D007676:Kidney Failure, Chronic / Q000378:metabolism*; D000077213:Lamotrigine; D008297:Male; D008875:Middle Aged; D006435:Renal Dialysis; D014227:Triazines / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine
D000927:Anticonvulsants; D005965:Glucuronates; D014227:Triazines; D000077213:Lamotrigine