Drugs online research references
Br J Clin Pharmacol. 1987 May;23(5):545-51.
Reduction of metformin renal tubular secretion by cimetidine in man.
Somogyi A, Stockley C, Keal J, Rolan P, Bochner F.
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.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3593625&dopt=Abstract
Metabolism. 1987 Aug;36(8):774-6.
Direct effects of biguanides on glucose utilization in vitro.
Purrello F, Gullo D, Brunetti A, Buscema M, Italia S, Goldfine ID, Vigneri R.
The effect of the biguanides metformin and phenformin on glucose utilization in isolated cells was studied with IM-9 human lymphocytes. Both agents stimulated glucose consumption from the incubation media. Detectable effects of metformin were seen at 33 mumol/L and detectable effects of phenformin were seen at 1.7 mumol/L. Both agents, at similar concentrations, also stimulated [3H] 2-deoxy-D-glucose uptake. Studies with phenformin indicated that biguanides increase the Vmax of uptake without changing the Km. In contrast to the biguanides, IM-9 cells insulin did not influence either glucose consumption or [3H] 2-deoxy-D-glucose uptake. These data provide evidence, therefore, that biguanides may directly influence the cellular utilization of glucose.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3600289&dopt=Abstract
Diabete Metab. 1979 Mar;5(1):5-9.
Effects of biguanides on the intermediate metabolism of glucose in normal and portal-strictured rats.
Schlienger JL, Frick A, Marbach J, Freund H, Imler M.
Phenformin and metformin treatments may be complicated by lactic adidosis. This metabolic complication seems favoured by preexistent hepatic disease. We have therefore compared the metabolic effects of phenformin and metformin on non fasting normal and portal-strictured rats. The latter group is characterized by impaired hepatic passage of these drugs without hepatocellular lesions. Given orally to normal rats over 5 days, phenformin (20 mg/kg/24 h) and metformin (150 mg/kg/24 h) decreased blood glucose levels and increased blood urea and the substrates of gluconeogenesis (alanine, glutamine, lactic and pyruvic acids), effects more apparent with phenformin than metformin. In non-treated portal strictured rats, blood glucose levels were lower and the intermediate metabolites were higher than in noraml rats, suggesting a modification of gluconeogenesis. Treatment of the portal strictured group by phenformin or metformin induced no changes in the studied parameters. This absence of effect of the biguanides in portal strictured rats supports the postulate that, in normal rats, biguanides act principally on hepatic metabolism by reducing gluconeogenesis and that, in the absence of other hepatic damage, the presence of a peri-hepatic shunt, which, by itself, modifies gluconeogenesis, does not further predispose to lactic acidosis during short term administration of biguanides.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=446834&dopt=Abstract
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