Biguanides absorption

The ultraviolet spectra of a number of substituted arylbiguanides have been recorded and the effects of various substituents in both the aryl and biguanide moiety examined 608) (see Table 5). SimUaiities in the absorption properties of arylbiguanides and acetanilides are noteworthy. 

Four groups of drugs have been shown to affect the absorption of vitamin B12. These include the oral hypoglycemic biguanides, colchicine, ethanol, and aminosalicylic acid. 

The different mechanisms of action of the various classes of hypoglycemic drugs makes combined therapy feasible the sulfonylureas and meglitinides stimulate insulin production by different mechanisms, the biguanides reduce glucose production by the liver and excretion from the liver, acarbose reduces the absorption of glucose from the gut, and the thiazolidinediones reduce insulin resistance in fat. It is not necessary to wait until the maximal dose of... 

Metformin can cause reduced vitamin Bi2 absorption, reducing serum Bi2 concentrations and causing megaloblastic anemia (87), the prevalence of which was 9% in 600 patients with type 2 diabetes taking biguanides (phen-formin or metformin) for a mean of 12 years (88). In 353 patients with type 2 diabetes, treated with insulin, who took metformin for 16 weeks in a placebo-controlled study, metformin increased serum homocysteine concentrations by 4% and reduced serum folate by 7% and vitamin Bi2 by 14% (89). 

Biguanides inhibit the enteric absorption of glucose. Owing to appetite loss the patient is forced to take smaller meals. They do not work when given parenterally. 

Metformin has an absolute oral bioavailability of about 50-60% of the dose after oral application of a single dose. Deconvolution analysis showed that after a short lag-time, the available remainder of the oral dose was absorbed at an exponential rate over about 6 h (Tucker et al., 1981). The bioavailability of phenformin seems to be more variable but also in the range of about 50% (Beckmann, 1968 Travis and Sayers, 1970). In general, absorption of biguanides is slower than their elimination, hence the plasma levels follow flip-flop kinetics (Pentikainen et al., 1979). 

Metformin hydrochloride is a biguanide that decreases blood glucose by decreasing hepatic glucose production. It may also decrease intestinal absorption of glucose and increase response to insulin. Metformin is indicated as an adjunct to diet and exercise to lower blood glucose in patients with type 2 diabetes mellitus. Metformin IR tablets and oral solution are indicated in patients 10 years of age and older. The ER tablets are indicated in patients 17 years of age and older. In combination with a sulfonylurea or insulin to improve glycemic control, metformin is indicated in patients 17 years of age and older. 

---