[Does ranitidine alter the pharmacokinetic of metformin?]

ABSTRACT

As Metformin is prescribed for a long-term therapy, it may be coadministered with a lot of other medicines. Ranitidine is a cationic drug and theoretically could decrease the excretion of metformin by competing for renal tubular transport. Increased metformin levels may increase the risk of lactic acidosis, in type II diabetic patients. The main goal of study the pharmacokinetics of Metformin is to help physicians to determine the accurate dose of Metformin, that enable them to have good glycemic control in patient with type II diabetes mellitus. Many medicines alter the pharmacokinetics of Metformin use and that make modifying of the dose necessary. An overview of metformin in the treatment of type II diabetes mellitus was studied by Davidson and Peters [1997]. Marked hypoglycemia was seen in patients on Glibenclamide when treated with Ranitidine [Lee et al; 1987], and another report briefly describes hypoglycemia in two patients given Cimetidine, and two other given Ranitidine, while taking un-named sulfonylureas [Girardin et al. 1992]. Another study reported that the hypoglycemic effect was reduced by Cimetidine and Ranitidine [Guthrie 1996]. In general view of the potential interactions, which may ultimately be hazardous due to long-term therapy of metformin with H2 receptor antagonists, the present study is focused on drug interactions of metformin with the commonly prescribed H2 receptor antagonist Ranitidine at human body temperature. This research aims to study the interaction between Metformin and one of another medicines which are commonly used together. We choose to study the interaction between the Ranitidine and Metformin, in patients with type II diabetes mellitus. Especially when different studies, about the coadministration of metformin and antacids, was contradictories, and was realized in lab. conditions not in humans. Fifteen male volunteers [25-40 years] received oral Metformin [500 mg every 12 hours] for 4 days, Ranitidine [150 mg every 12 hours] in combination of oral Metformin [500 mg every 12 hours] for 4 days. Plasma samples were collected on day 4 of each regimen. The result showed that coadministration of Metformin and Ranitidine had no significant effects on the steady state pharmacokinetics [AUC 0-12 h, Cmax, Tmax or Tl/2] of Metformin in patient with type II diabetes mellitus