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PHENFORMIN 4-HYDROXYLATION

PHENFORMIN 4-HYDROXYLATION

Phenformin is a biguanide that was formerly used as an oral hypoglycemic agent in maturity-onset diabetes. It is rapidly absorbed and metabolized exclusively by ...

Phenformin is a biguanide that was formerly used as an oral hypoglycemic agent in maturity-onset diabetes. It is rapidly absorbed and metabolized exclusively by p-hydroxylation to a single metabolite, 4-hydroxyphenformin. The unchanged drug and its metabolite are cleared from the blood virtually exclusively by the kidneys. About two-thirds of an oral dose is excreted in the urine within 8 hours as the unchanged drug plus its metabolite. Shah et al. (1985) found that about 9% of a London population had a defect in p-hydroxylation of phenformin, inherited as an autosomal recessive. Phenformin was withdrawn from the market because it was often associated with lactic acidosis which could be fatal. Persons with the metabolic defect may have been more susceptible to this complication. Shah et al. (1985) reviewed the evidence that the same genetic defect may be responsible for both impaired debrisoquine oxidation (124030) and impaired phenformin 4-hydroxylation.

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