Mar 1, 1991

Hexamethylmelamine: pharmacology and mechanism of action

Cancer Treatment Reviews
M M Ames

Abstract

Several conclusions can be drawn from a review of HMM preclinical and clinical pharmacology data. The drug is extensively metabolized by animals and by man. The drug is well absorbed following oral administration to animals, but oral bioavailability is low due to first pass metabolism. Based on limited human data and more complete animal data, absorption of HMM following oral administration may be quite high in man. We do not yet know the oral bioavailability of HMM in patients, but again based primarily on animal studies, oral bioavailability is most likely low and variable due to extensive first pass metabolism. Systemic exposure to HMM and demethylated metabolites following oral administration varies greatly from patient to patient and is sometimes quite low. Most patients are, however, exposed to a substantial fraction of the administered dose when determined by urinary recovery of the total dose (based on parent drug and metabolites or total radioactivity) or by the total plasma AUC of parent drug and all metabolites. Systemic exposure to HMM following intravenous administration is clearly greater and less variable than following oral administration. An unresolved question is whether the highly variable and often low syste...Continue Reading

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Citations

Mentioned in this Paper

Metabolic Process, Cellular
Clinical Pharmacology Discipline
Metabolic Pathway
Drug Evaluation
Metabolite
Activation, Metabolic
Metabolism
Altretamine
Dye Exclusion Assays, Antitumor
Metabolic Aspects

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