In Vivo Pharmacokinetic Interactions of Finasteride and Identification of Novel Metabolites

This thesis aimed to enhance the understanding of the in vivo pharmacokinetics and metabolism of finasteride, a drug used for treating enlarged prostate and male pattern baldness. It identified CYP3A4 as the primary enzyme responsible for metabolizing finasteride into ω-OH finasteride (M1) and ω-COOH finasteride (M3). Studies in humans and pigs showed that induced metabolism decreased plasma exposure of finasteride, while inhibited metabolism increased it. The research detailed the biliary pharmacokinetics and hepatic extraction of finasteride and its metabolites, revealing that M3's excretion involved carrier-mediated processes, unlike finasteride. M1 was not quantifiable, but its isomers were identified and found to undergo glucuronide conjugation. The findings advanced the understanding of finasteride's pharmacokinetics and could be applicable to other drugs.