Phenformin absorption

The most common toxic effects of metformin are gastrointestinal (anorexia, nausea, vomiting, abdominal discomfort, and diarrhea), which occur in up to 20% of patients. They are dose-related, tend to occur at the onset of therapy, and are often transient. However, metformin may have to be discontinued in 3-5% of patients because of persistent diarrhea. Absorption of vitamin B12 appears to be reduced during long-term metformin therapy, and annual screening of serum vitamin B12 levels and red blood cell parameters has been encouraged by the manufacturer to determine the need for vitamin B12 injections. In the absence of hypoxia or renal or hepatic insufficiency, lactic acidosis is less common with metformin therapy than with phenformin therapy. 

Megaloblastic anemia is rare with metformin, but vitamin Bi2 concentrations can be reduced by metformin and phenformin (92) because of reduced absorption, and pre-existing deficiency can be exacerbated (64). 

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). 

Malabsorption of vitamin B12 was observed in 14 of 46 diabetics taking metformin or phenformin (Callaghan et al., 1980 Adams et al., 1983) metformin was more often to blame. Withdrawal of the drug resulted in normal absorption in only 7 of the 14 (Adams et al., 1983). 

A report suggests that the hypocholesterolaemic effect of colestipol is unaffected in insulin-treated diabetics but it may be ineffective in those taking phenformin and sulphonylureas. Diabetic control was not affected. Colestyramine may enhance the effect of acarbose, and insulin levels may rebound if both drugs are stopped at the same time. There is evidence that the absorption of glipizide may be reduced by about 30% if it is taken at the same time as colestyramine, but tolbutamide does not appear to be affected. 

Phenformin - The recent status of the mechanism of action of phenformin, has been thoroughly reviewed >. There have been additional reports on the anorexigenic effect, or lack thereof, and on the inhibitory effect of the drug on the rate of intestinal glucose absorption. Although phenformin increases the tolerance to orally administered glucose, it has no effect on intravenous glucose tolerance in hximans . 

---