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.
Defective hydroxylation of phenformin as a determinant of drug toxicity / E. Bosisio, M. G. Kienle, G. Galli, M. Ciconali, A. Negri, A. Sessa, S. Morosati, C. R. Sirtori. - In: DIABETES. - ISSN 0012-1797. - 30:8(1981 Aug), pp. 644-649.
|Titolo:||Defective hydroxylation of phenformin as a determinant of drug toxicity|
BOSISIO, ENRICA ANGELA (Primo)
SIRTORI, CESARE (Ultimo)
|Parole Chiave:||Phenformin; Diabetic Nephropathies; Half-Life; Kinetics; Humans; Aged; Middle Aged; Male; Female; Hydroxylation|
|Settore Scientifico Disciplinare:||Settore BIO/14 - Farmacologia|
|Data di pubblicazione:||ago-1981|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.2337/diab.30.8.644|
|Appare nelle tipologie:||01 - Articolo su periodico|