title: Preclinical Pharmacokinetic Evaluation of β-Lapachone: Characteristics of Oral Bioavailability and First-Pass Metabolism in Rats.
abstract: β-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 β-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 β-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 β-lapachone at doses of 40 mg/kg and 1.5 mg/kg, respectively. The measured oral bioavailability of β-lapachone was 15.5%. The considerable degradation of β-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 β-lapachone may be resulted from the first-pass metabolic degradation of β-lapachone in the liver, small and large intestinal tracts and its low aqueous solubility.
authors.affiliation: College of Pharmacy, Chung-Ang University, Seoul 156-756.
authors.forename: Iksoo
authors.initials: I
authors.lastname: Kim
authors.affiliation: College of Pharmacy, Chung-Ang University, Seoul 156-756.
authors.forename: Hyeongmin
authors.initials: H
authors.lastname: Kim
authors.affiliation: College of Pharmacy, Chung-Ang University, Seoul 156-756.
authors.forename: Jieun
authors.initials: J
authors.lastname: Ro
authors.affiliation: College of Pharmacy, Chung-Ang University, Seoul 156-756.
authors.forename: Kanghee
authors.initials: K
authors.lastname: Jo
authors.affiliation: College of Pharmacy, Chung-Ang University, Seoul 156-756.
authors.forename: Sandeep
authors.initials: S
authors.lastname: Karki
authors.affiliation: College of Pharmacy, Chung-Ang University, Seoul 156-756.
authors.forename: Prakash
authors.initials: P
authors.lastname: Khadka
authors.affiliation: Department of Food Science and Technology, Chung-Ang University, Anseong 456-756, Republic of Korea.
authors.forename: Gyiae
authors.initials: G
authors.lastname: Yun
authors.affiliation: College of Pharmacy, Chung-Ang University, Seoul 156-756.
authors.forename: Jaehwi
authors.initials: J
authors.lastname: Lee
keywords: Bioavailability; Metabolism; Pharmacokinetics; Preclinical; β-Lapachone