Reduction of metformin renal tubular secretion by cimetidine in man
Abstract
To determine whether cimetidine altered the renal handling of metformin, seven subjects took 0.25 g metformin daily with and without cimetidine 0.4 g twice daily. Blood and urine samples were collected and assayed for metformin, cimetidine and creatinine by h.p.l.c. Cimetidine significantly increased the area under the plasma metformin concentration-time curve by an average of 50% and reduced its renal clearance over 24 h by 27% (P less than 0.008). There was no alteration in the total urinary recovery of metformin when cimetidine was co-administered. The effect of cimetidine on the renal clearance of metformin was time dependent, being significantly reduced up to 6 h following cimetidine. These results appeared to be consistent with competitive inhibition of renal tubular secretion. Cimetidine had no effect on the renal clearance of creatinine, but time-dependent variations in both metformin and creatinine renal clearance were observed. Metformin had no effect on cimetidine disposition. It is concluded that cimetidine inhibits the renal tubular secretion of metformin in man, resulting in higher circulating plasma concentrations. Because of its propensity for causing dose and concentration-dependent adverse effects, the dose of metformin should be reduced when cimetidine is co-prescribed.
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