A pharmacokinetic study of roxatidine acetate in chronic renal failure

The pharmacokinetics of a single oral dose of roxatidine acetate 150 mg were studied in 31 patients with varying degrees of chronic renal failure. The patients were divided into 5 groups according to their creatinine clearance (Clcr): controls (Clcr 94.5 +/- 13.9 ml/min; n = 6); mild chronic renal failure (Clcr 47 +/- 6 ml/min; n = 4); moderate chronic renal failure (Clcr 27.3 +/- 3.1 ml/min; n = 4); severe chronic renal failure (Clcr 12.8 +/- 1.4 ml/min; n = 5) and uraemia (Clcr 6.6 +/- 0.6 ml/min; n = 12). Serum and urine samples were analysed with capillary gas chromatography to measure the salt of the desacetyl metabolite of roxatidine acetate (roxatidine). The terminal half-life was 6.02 +/- 0.31 hours in controls and 7.35 +/- 0.57, 9.3 +/- 0.83, 14.6 +/- 3.7 and 18.10 +/- 2.77 hours, respectively, in the 4 other groups, with progressively decreasing creatinine clearance. Maximum serum concentration and time to maximum serum concentration rose from 816 +/- 75 ng/ml and 2.08 +/- 0.22 hours, respectively, in controls to 1364.7 +/- 156 ng/ml and 4.05 +/- 0.47 hours, respectively, in uraemic patients. Relative total clearance progressively decreased with decreasing glomerular filtration rate (GFR) [from 353.6 +/- 26 ml/min in controls to 90.31 +/- 12.2 ml/min in patients with uraemia]. Renal clearance decreased from a control of 243.9 +/- 56 ml/min to 12.32 +/- 0.18 ml/min in uraemic patients. A linear correlation between creatinine clearance and both relative total clearance and renal drug clearance was noted.(ABSTRACT TRUNCATED AT 250 WORDS)