4-hydroxyphenformin has been researched along with Diabetic-Nephropathies* in 1 studies
1 other study(ies) available for 4-hydroxyphenformin and Diabetic-Nephropathies
Article | Year |
---|---|
Defective hydroxylation of phenformin as a determinant of drug toxicity.
The kinetics of phenformin and its metabolite, p-hydroxyphenethylbiguanide, was studied in eight diabetic patients with varying degrees of renal impairment. Plasma and urinary phenformin and p-hydroxyphenethylbiguanide levels were determined by the multiple selected ion monitoring technique. Phenformin half-lives were unrelated to the degree of renal impairment, whereas reduced renal clearances of insulin and creatinine were significantly correlated with a prolonged half-life of the metabolite. The excretion of p-hydroxyphenethylbiguanide was quite variable (between 4.9% and 27% of total urinary drug loss), probably due to a genetic polymorphism of hepatic mechanisms for hydroxylation. A reduced formation of the metabolite was concomitant with marked increases in the amount of circulating phenformin. A positive reciprocal correlation was detected between areas under the plasma curve of phenformin and both the renal clearance of the unchanged drug and the percentage of metabolite formation. A reduced hydroxylation of phenformin seems, therefore, to be responsible for the high plasma levels of the drug previously described in toxic patients. Topics: Aged; Diabetic Nephropathies; Female; Half-Life; Humans; Hydroxylation; Kinetics; Male; Middle Aged; Phenformin | 1981 |