Comparative pharmacokinetics of puerarin in pure compound form and puerarin in white kwao krua extract in female cynomolgus monkeys

Abstract

Pueraria mirifica is an endemic Thai plant that puerarin is a major chemical found in this plant and shows several pharmacological activities in aging diseases. Although the pharmacokinetic data on puerarin have been reported in rodents, it is still inconclusive for the development of puerarin as phytopharmaceutical products for human use. This is because of the differences in anatomical and physiological characteristics between rodents and humans. Therefore, the comparative pharmacokinetics of puerarin in pure compound form (PUE) and puerarin in P. mirifica extract (PME) was conducted in female cynomolgus monkeys. PME at a dose of 826 mg/kg.BW (equivalent to 10 mg/kg.BW of puerarin) and PUE at a dose of 10 mg/kg.BW were daily orally administered to monkeys for 7 consecutive days. A single intravenous injection of 1 mg/kg.BW of PUE was also performed for the bioavailability analysis of puerarin orally administered to monkeys. Serial blood samples and excreta (urine and feces) were collected after dosing at designated times. The levels of puerarin in biological samples were determined by liquid chromatography tandem mass spectrometry. After PME and PUE orally dosing to monkeys, plasma levels of aspartate aminotransferase and alanine aminotransferase which were indicated the liver function, and plasma creatinine levels which were indicated the kidney function were fluctuated in the normal range, with no abnormal physical signs in animals. The absolute oral bioavailability of puerarin was 1.44% after the PME oral dosing and 0.88% after the PUE oral dosing, but the T1/2 was prolonged for nearly two times in the PUE group (4.78 h) comparing to the PME group (2.61 h). After 7-day multiple oral dosing of puerarin in both preparations, the accumulations were occurred in the body of the animals. Major metabolite pathways of puerarin found in monkeys were hydroxylation and deglycosylation before excreted via urine and feces. A negligible amount of unchanged puerarin was detected for less than 1% in urine and feces. In conclusion, an oral dosing of a puerarin shows the better absorption in the extract form than in the pure compound form, but it has a shorter half-life. Puerarin can be accumulated in the body of the animals when it is continuously orally dosing. Thus, the pharmacokinetic profiles obtained from female cynomolgus monkeys in this study could help to design the prescribed remedy of the oral administration of puerarin as phytopharmaceutical products for human use.