Comparative bioavailability of a lipophilic steroid

Area of Science:

• Pharmacology
• Reproductive Science
• Drug Delivery

Background:

• 17beta-Acetoxy-2alpha-chloro-3-(p-nitrophenoxy)imino-5alpha-androstane (I) is a lipophilic steroid with antifertility properties.
• Understanding its bioavailability is crucial for effective therapeutic application.

Purpose of the Study:

• To compare the bioavailability of micronized I from solutions versus suspensions.
• To investigate the impact of formulation on drug absorption in rats and preliminary human data.

Main Methods:

• Adult female Wistar rats received varying concentrations of micronized 3H-I in sesame oil via oral gavage.
• Blood and urine samples were collected and assayed for radioactive content.
• Absorption was determined by analyzing radioactivity in blood and urine, with preliminary human data comparing sesame oil to lactose formulations.

Main Results:

• A significantly higher fraction of the dose was absorbed when I was formulated in solution compared to suspension.
• A linear relationship between absorbed dose and administered dose was observed primarily for solution formulations.
• Preliminary human data indicated greater absorption of 3H-I in sesame oil versus lactose.

Conclusions:

• Formulation as a solution significantly enhances the oral bioavailability of micronized I.
• Sesame oil appears to be a superior vehicle for oral drug delivery of I compared to lactose.
• These findings have implications for optimizing the delivery and efficacy of this antifertility steroid.