Speaker
Description
Background: Compound Danshen droplet pill, containing Salvia miltiorrhiza root (Danshen), Panax notoginseng root (Sanqi), and Borneolum syntheticum (Bingpian), is widely used for chronic stable angina. Two key pharmacokinetic questions are: “Which constituents are of significantly oral bioavailability and so merit pharmacodynamic study?” and “Whether the pill’s components are of pharmacokinetic compatibility (PKC, absence of adverse drug interaction)？”
Methods: Human plasma/urine samples post-dose were analyzed by LC/MS and GC/MS. To evaluate the pill’s PKC, the major circulating compounds were assessed in vitro with respect to their inhibition and induction of human drug metabolizing enzymes and transporters that govern the compounds’ systemic exposure.
Results: Constituents (compound dose, 0.01–96.1 μmol/day) detected in the pill were 25 phenolic acids and 12 diterpene quinones originating from Danshen, 34 triterpene saponins from Sanqi, and three monoterpenes from Bingpian. After dosing, major circulating compounds were mostly metabolites: tanshinol and its methylated forms, protocatechuic acid derivatives (from Danshen); protopanaxatriol and its oxidized metabolites (from Sanqi); borneol, isoborneol, their glucuronides and camphor (from borneol). They showed weak inhibition of CYP3A, CYP2A6, CYP2B6, UGT2B7, ALDH, COMT, OATs (DDI indices 0.005–0.019) and no significant induction of CYP3A4/CYP2B6, indicating high PKC.
Conclusions: Most of the major circulating compounds after orally dosing the pill are metabolites, rather than their parent constituents. This finding allows pharmacodynamic studies of the pill to be conducted with the ‘right’ potentially important compounds. The high degree of PKC limits the impact of pharmacokinetic DDIs on the pill’s multifaceted antianginal action.