Comparison of Berberine Bioavailability between Oral and Rectal Administrations in Rats

Area of Science:

• Pharmacology
• Drug Delivery Systems
• Pharmacokinetics

Background:

• Berberine (BBR) exhibits low oral bioavailability due to extensive first-pass metabolism.
• First-pass metabolism in the intestine and liver significantly limits BBR's systemic exposure.
• Alternative administration routes are needed to overcome these pharmacokinetic limitations.

Purpose of the Study:

• To evaluate the efficacy of rectal administration of berberine sulfate to enhance bioavailability.
• To compare the pharmacokinetic profile of rectally administered BBR sulfate with oral and intravenous routes.
• To assess the potential of rectal delivery to mitigate first-pass metabolism of BBR.

Main Methods:

• Berberine sulfate was administered intravenously (1 mg/kg), orally (10 mg/kg), and rectally (1, 3, 10 mg/kg) in rats.
• Rectal formulations utilized Witepsol® H15 suppository base.
• Plasma BBR concentrations were quantified using liquid chromatography-tandem mass spectrometry (LC-MS/MS).

Main Results:

• Oral administration resulted in an average oral bioavailability of 0.26%.
• Rectal administration yielded significantly higher average bioavailabilities: 17.0% (1 mg/kg), 24.3% (3 mg/kg), and 12.3% (10 mg/kg).
• Rectal delivery markedly improved BBR bioavailability compared to the oral route.

Conclusions:

• Rectal administration of berberine sulfate substantially increases BBR bioavailability in rats.
• This enhanced bioavailability via the rectal route is attributed to the avoidance of significant first-pass metabolism.
• Rectal delivery of BBR sulfate holds promise for improving its therapeutic efficacy in vivo.