Effects of puerarin on the pharmacokinetics of triptolide in rats

Abstract

Context: Puerarin and triptolide are sometimes used together for the treatment of disease in Chinese clinics; however, the drug-drug interaction between puerarin and triptolide is still unknown. Objective: This study investigates the effects of puerarin on the pharmacokinetics of triptolide in rats and clarifies its main mechanism. Materials and methods: The pharmacokinetic profiles of oral administration of triptolide (1 mg/kg) in Sprague-Dawley rats with (test group, n ¼ 6) or without pretreatment (control group, n ¼ 6) with puerarin (100 mg/kg/day for seven days) were investigated. The effects of puerarin on the transport and metabolic stability of triptolide were also investigated using Caco-2 cell transwell model and rat liver microsomes. Results: The results showed that puerarin could significantly increase the peak plasma concentration (from 187.25 ± 15.36 to 219.67 ± 21.52 ng/mL), and decrease its oral clearance (from 4.92 ± 0.35 to 62.46 ± 3.75 ± 0.19 L/h/kg). The Caco-2 cell transwell experiments indicated that puerarin could decrease the efflux ratio of triptolide from 2.70 to 1.33, and the intrinsic clearance rate of triptolide was decreased by the pretreatment with puerarin (38.8 ± 4.7 vs. 32.9 ± 6.5 lL/min/mg protein). Discussion and conclusions: Puerarin could significantly change the pharmacokinetic profiles of triptolide in rats, and it might exert these effects through increasing the absorption of triptolide by inhibiting the activity of P-gp, or through inhibiting the metabolism of triptolide in rat liver. The results also showed that the dose of triptolide should be decreased when these drugs were co-administered.

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

“…Drug metabolizing reaction was reported in the PUE treated rats. It was shown that PUE inhibits the activity of P-gp or CYP3A4 [43]. P-gp is an ATP-dependent transmembrane efflux pump that is expressed in columnar epithelial cells of the lower gastrointestinal tract and canalicular surface of hepatocytes [44].…”

“…Since the intestinal bioavailability (FI=F/[FH*Fa]) in female cynomolgus monkeys is very low (about 0.012 or 1.2 %), this suggests that the intestine plays a major role in the metabolism of PUE. The plausible enzymes in intestinal enterocytes metabolizing the PUE are P-gp and CYP3A [43]. PUE was reported as a plausible substrate of P-gp [47].…”

Effects of puerarin on the pharmacokinetics of astragaloside IV in rats and its potential mechanism

“…The test group was pre-treated with puerarin at a dose of 100 mg/kg/day (dissolved directly in normal saline containing 0.5% methylcellulose at a concentration of 2 mg/mL) for 7 days before the administration of AS-IV. Next, AS-IV was orally administered to rats by gavage at a dose of 20 mg/kg (Du et al 2005;Wang et al 2019). Blood samples (250 lL) were collected into heparinized tubes via the oculi chorioideae vein at 0.083, 0.33, 0.5, 1, 2, 4, 6, 8, 10, 12 and 24 h after the oral administration of puerarin.…”

Pharmacokinetics and drug delivery systems for puerarin, a bioactive flavone from traditional Chinese medicine

“…On the contrary, puerarin could affect the pharmacokinetics of some active compounds which were substrates of P-gp, MRP and CYP 450. Puerarin could significantly change the pharmacokinetic profiles of triptolide in rats probably though inhibiting the activity of P-gp or CYP3A4 (Wang et al., 2019). CYP3A4 enzyme was also involved in the metabolism of ivabradine, the AUC and C max of ivabradine in rats that were pretreated with puerarin were significantly higher than that of the ivabradine control group (Zhang et al., 2016).…”