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

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.

A Phase III, Randomized, Double-Blind, Matched-Pairs, Active-Controlled Clinical Trial and Preclinical Animal Study to Compare the Durability, Efficacy and Safety between Polynucleotide Filler and Hyaluronic Acid Filler in the Correction of Crow's Feet: A

The Rejuran(R) is a new filler product made from purified polynucleotides. Here we present data from an animal study and a clinical trial to examine the durability, efficacy and safety of the Rejuran(R) on crow's feet. For the animal study, 25 mice were divided into three groups: Group 1 received phosphate buffered saline (PBS); Group 2 were treated with Yvoire(R); and Group 3 were treated with Rejuran(R). The durability and efficacy of each treatment were assessed by microscopy and staining. In the clinical trial, 72 patients were randomized to receive Rejuran(R) treatment for crow's feet on one side and Yvoire-Hydro(R) on the contralateral side, at a ratio of 1:1. Repeated treatments were performed every two weeks for a total of three times, over a total of 12 weeks' observation. All injections and observations of efficacy and safety were performed by the same two investigators. In the animal study, the Rejuran(R) group showed similar durability and inflammatory response to the Yvoire(R) group. Upon efficacy assessment, the Rejuran(R) group showed the greatest elasticity and collagen composition, and a significant difference in skin surface roughness and wrinkle depth. In the clinical trial, the primary and secondary objective efficacy outcome measure showed no statistical significance between the two groups, and in safety outcomes there were no unexpected adverse effects. Our data suggest that the Rejuran(R), as a new regenerative filler, can be useful to reduce wrinkles, by showing evidence for its efficacy and safety.