Bioavailability and pharmacokinetic comparison of tanshinones between two formulations of Salvia miltiorrhiza in healthy volunteers

Abstract

Abstract Salvia miltiorrhiza (SM) is widely used to treat microcirculatory disturbance-related diseases; its lipophilic components play important roles in this application. Cryptotanshinone (CTS), tanshinone I (TSI) and tanshinone IIA (TSA) are the most widely-studied lipophilic ingredients, but low oral bioavailability limits their clinical application. It has been proven that micronization could improve the bioavailability of some drugs, so we’ve conducted this randomized study to investigate whether micronized granular powder (GP) of SM could improve the bioavailability of tanshinones compared with traditional decoction (TD). An oral dose of TD or GP of SM was administrated to subjects and blood samples were collected at predetermined time points. The plasma concentrations of tanshinones were detected by a validated method and pharmacokinetic parameters were calculated using a non-compartmental model. GP of SM resulted in a significant increase in mean maximum plasma concentration (C max ), elimination half-life and area under concentration-time curve (AUC) of tanshinones, with the plasma AUC of CTS, TSI and TSA in GP 5–184, 4–619 and 5–130 times higher than TD. In addition, the individual variances of C max and AUC were much lower after GP administration. Summarily, tanshinones in micronized GP of SM had higher oral bioavailability and lower individual variances, thus we speculate that it may indicate a better clinical efficacy and be a better choice than current treatments.