Preclinical Pharmacokinetic Evaluation of beta-Lapachone: Characteristics of Oral Bioavailability and First-Pass Metabolism in Rats.
10.4062/biomolther.2015.029
- Author:
Iksoo KIM
1
;
Hyeongmin KIM
;
Jieun RO
;
Kanghee JO
;
Sandeep KARKI
;
Prakash KHADKA
;
Gyiae YUN
;
Jaehwi LEE
Author Information
1. College of Pharmacy, Chung-Ang University, Seoul 156-756, Republic of Korea. jaehwi@cau.ac.kr
- Publication Type:Original Article
- Keywords:
beta-Lapachone;
Preclinical;
Pharmacokinetics;
Bioavailability;
Metabolism
- MeSH:
Administration, Intravenous;
Administration, Oral;
Animals;
Biological Availability*;
Chromatography, High Pressure Liquid;
Dosage Forms;
Intestines;
Liver;
Metabolism*;
Pharmacokinetics;
Plasma;
Rats*;
Solubility
- From:Biomolecules & Therapeutics
2015;23(3):296-300
- CountryRepublic of Korea
- Language:English
-
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.
