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.