Effect of ophiopogonin D on the pharmacokinetics and transport of cryptotanshinone during their co‐administration and the potential mechanism

Cryptotanshinone and ophiopogonin D are sourced from herbs with similar indications. It is necessary to evaluate their interaction to provide a reference for their clinical prescriptions. The co-administration of cryptotanshinone (30 and 60 mg/kg) and ophiopogonin D was carried out in Sprague-Dawley rats and the pharmacokinetics of cryptotanshinone were analyzed. The Caco-2 cells were employed to evaluate the transport of cryptotanshinone, and the metabolic stability was studied in the rat liver microsomes. Ophiopogonin D significantly increased the Cmax (from 5.56 ± 0.26 to 8.58 ± 0.71 μg/mL and from 15.99 ± 1.81 to 185.12 ± 1.43 μg/mL), half-life (21.72 ± 10.63 vs. 11.47 ± 3.62 h and 12.58 ± 5.97 vs. 8.75 ± 2.71 h) and decreased the clearance rate (0.697 ± 0.36 vs. 1.71 ± 0.15 L/h/kg) and (60 mg/kg and 0.101 ± 0.02 vs. 0.165 ± 0.05 L/h/kg) of cryptotanshinone. In vitro, ophiopogonin D significantly suppressed the transport of cryptotanshinone with the decreasing efflux rate and enhanced the metabolic stability with the reducing intrinsic clearance. The combination of cryptotanshinone and ophiopogonin D induced prolonged exposure and suppressed the transport of cryptotanshinone, which indicated the decreased bioavailability of cryptotanshinone.