Absolute oral bioavailability and disposition kinetics of puerarin in female rats

Abstract

BackgroundPueraria candollei var. mirifica is a medicinal plant that is promoted as a “Champion Product” by the Government of Thailand. This plant has been reported to relieve postmenopausal symptoms, prevent and reverse bone loss, inhibit the growth of breast cancer, and alleviate cardiovascular diseases in preclinical and clinical studies. However, there is little information on the oral bioavailability and tissue distribution of puerarin with respect to its pharmacodynamic activities. Therefore, the aim of this study was to determine the pharmacokinetics of puerarin, including absorption, distribution, metabolism, and elimination, in rats. Moreover, this is the first study to examine the tissue distribution of puerarin in the hippocampus, femur, tibia, and mammary gland.MethodsAdult female rats were administered puerarin at 1 mg/kg intravenously or 5 and 10 mg/kg orally. Blood, tissue, urine, and feces were collected and analyzed by liquid chromatography–tandem mass spectrometry.ResultsPuerarin reached a maximum concentration in the blood of 140–230 μg/L within 1 h of oral dosing, and had an absolute oral bioavailability of approximately 7%. Following intravenous administration, puerarin was widely distributed in several tissues, including the hippocampus, heart, lung, stomach, liver, mammary gland, kidney, spleen, femur, and tibia. Approximately 50% of the intravenous dose was excreted as glucuronide metabolites via the urinary route.ConclusionsThe absolute oral bioavailability of puerarin was approximately 7% at doses of 5 and 10 mg/kg. Puerarin was widely distributed to several organs related to the diseases of aging, including the hippocampus, femur, tibia, and mammary gland. Glucuronides were the major metabolites of puerarin and were mainly excreted in the urine. These results are useful for the development of puerarin and Pueraria candollei var. mirifica as phytopharmaceutical products.

Preparation of Puerarin Chitosan Oral Nanoparticles by Ionic Gelation Method and Its Related Kinetics

“…However, Pur is a BCS IV drug with low oral bioavailability [6]. Oral Pur is mostly excreted in its original form through feces, and only a small part is absorbed into the blood and distributed to various tissues and organs [7,8]. At present, there are only injections and eye drops in clinical use, and the injections require long-term use, and also have poor compliance and are prone to intravascular hemolysis, allergic asthma, anaphylactic shock, fevers, and other adverse reactions [9,10].…”

Comparative Pharmacokinetics of Puerarin Alone and in Pueraria mirifica Extract in Female Cynomolgus Monkeys

“…served in the PME group compared to PUE alone. The oral bioavailability of PUE in nonhuman primates was lower than that previously reported in rodents (1.0 vs. 7.0 %) [20]. One possible explanation is that the small intestine of cynomolgus monkey had a lower membrane permeability than those in rats [41].…”

Herb–drug interaction studies of herbs used in treatment of cardiovascular disorders—A narrative review of preclinical and clinical studies

“…Puerarin is the most abundant isoflavone compound obtained from the roots and responsible for cardioprotective and anti‐hypertensive action (Shibata et al, ). The amount of puerarin present in Radix puerariae is about 0.3570 ± 0.0016 mg/g with reported oral bioavailability of 7% (Anukunwithaya et al, ; Yu, Yan, Zhen, & Rao, ). Different in vitro and in vivo experiments along with clinical investigations showed the Radix puerariae herbal extract or its total flavones products could increase micro‐circulation, improve blood flow, and prevent coronary artery diseases, as well as lower hypertension.…”