Biomol Ther.  2015 May;23(3):296-300. 10.4062/biomolther.2015.029.

Preclinical Pharmacokinetic Evaluation of beta-Lapachone: Characteristics of Oral Bioavailability and First-Pass Metabolism in Rats

• Kim I
• Kim H
• Ro J
• Jo K
• Karki S
• Khadka P
• Yun G
• Lee J

• KMID: 2380341
• DOI: http://doi.org/10.4062/biomolther.2015.029

Abstract

beta-Lapachone has drawn increasing attention as an anti-inflammatory and anti-cancer drug. However, its oral bioavailability has not been yet assessed, which might be useful to develop efficient dosage forms possibly required for non-clinical and clinical studies and future market. The aim of the present study was thus to investigate pharmacokinetic properties of beta-lapachone as well as its first-pass metabolism in the liver, and small and large intestines after oral administration to measure the absolute bioavailability in rats. A sensitive HPLC method was developed to evaluate levels of beta-lapachone in plasma and organ homogenates. The drug degradation profiles were examined in plasma to assess the stability of the drug and in liver and intestinal homogenates to evaluate first-pass metabolism. Pharmacokinetic profiles were obtained after oral and intravenous administration of beta-lapachone at doses of 40 mg/kg and 1.5 mg/kg, respectively. The measured oral bioavailability of beta-lapachone was 15.5%. The considerable degradation of beta-lapachone was seen in the organ homogenates but the drug was quite stable in plasma. In conclusion, we suggest that the fairly low oral bioavailability of beta-lapachone may be resulted from the first-pass metabolic degradation of beta-lapachone in the liver, small and large intestinal tracts and its low aqueous solubility.

Keyword

beta-Lapachone; Preclinical; Pharmacokinetics; Bioavailability; Metabolism

MeSH Terms

Administration, Intravenous
Administration, Oral
Animals
Biological Availability*
Chromatography, High Pressure Liquid
Dosage Forms
Intestines
Liver
Metabolism*
Pharmacokinetics
Plasma
Rats*
Solubility
Dosage Forms