Pharmacokinetics of cimetidine and its sulphoxide metabolite during haemodialysis.
A single intravenous dose of cimetidine 200mg was administered to 6 patients with severe chronic renal failure one hour prior to haemodialysis. The plasma concentrations of cimetidine and its sulphoxide metabolite at the start of haemodialysis were 2.74 +/- 0.12 and 0.76 +/- 0.08 microgram/ml, and after dialysis for 4h 1.08 +/- 0.10 and 0.51 +/- 0.08 microgram/ml, respectively (mean +/- SE). The average haemodialysis clearance (ClHDa) of cimetidine during dialysis was 46-92 ml/min at a dialysate flow rate of 320 ml/min and blood flow rates in the 6 patients between 160-240 ml/min. The mean ClHDa of the sulphoxide metabolite was 44% higher than that of cimetidine, and ranged between 49-148 ml/min. During haemodialysis the mean plasma elimination half-life (t 1/2) of cimetidine was 3.24h (range 2.08-5.08) and of the sulphoxide metabolite 9.49h (range 4.70-14.39). There was a significant relationship between the elimination rate constant (beta) and ClHDa of the sulphoxide metabolite (p less than 0.01), but no such relationship was found between beta and ClHDa of cimetidine. The mean total amount of cimetidine eliminated during dialysis was 27.3mg (range 17.9-31.8), which was 9.0-15.9% of the given dose. Between 12.2-21.2mg (mean 15.3) of the sulphoxide metabolite was eliminated in the dialysate. Major adjustment of the dose of cimetidine on days of dialysis is not necessary.
D000328:Adult; D000368:Aged; D001711:Biotransformation; D001783:Blood Flow Velocity; D002927:Cimetidine / Q000378:metabolism*; D005260:Female; D006146:Guanidines / Q000378:metabolism*; D006801:Humans; D007676:Kidney Failure, Chronic / Q000378:metabolism* / Q000628:therapy; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D006435:Renal Dialysis; D013454:Sulfoxides / Q000378:metabolism*
D006146:Guanidines; D013454:Sulfoxides; D002927:Cimetidine