Sesquiterpene lactones (STLs) and diterpene lactones (DTLs) are two groups of common phytochemicals with similar structures. It's frequently reported that both exhibit changeable pharmacokinetics (PK) in vivo, especially the unstable absorption and extensive metabolism. However, the recognition of their PK characteristics is still scattered. In this review, representative STLs (atractylenolides, alantolactone, costunolide, artemisinin, etc.) and DTLs (ginkgolides, andrographolide, diosbulbins, triptolide, etc.) as typical cases are discussed in detail. We show how the differences of treatment regimens and subjects alter the PK of STLs and DTLs, with emphasis on the effects from absorption and metabolism. These compounds tend to be quite permeable in intestinal epithelium, but gastrointestinal pH and efflux transporters (represented by P-glycoprotein) have great impact and result in the unstable absorption. As the only characteristic functional moiety, the metabolic behavior of lactone ring is not dominant. The α, β-unsaturated lactone moiety has the strongest metabolic activity. While with the increase of low-activity saturated lactone moieties, the metabolism is led by other groups more easily. The phase I (oxidation, reduction and hydrolysis reaction) and II metabolism (conjugation reaction) are both extensive. CYP450s, mainly CYP3A4, are largely involved in biotransformation. However, only UGTs (UGT1A3, UGT1A4, UGT2B4 and UGT2B7) has been mentioned in studies about phase II metabolic enzymes. Our work offers a beneficial reference for promoting the safety evaluation and maximizing the utilization of STLs and DTLs.
Keywords: Sesquiterpene lactone; absorption; diterpene lactone; metabolism; pharmacokinetics.