How are CGA and CA metabolized and cleared in vivo?

Phase I/II metabolism can either activate, inactivate or toxify phytochemicals; understanding routes informs dosing and safety.

CGA bypasses cytochrome P450-mediated phase I oxidation and is directly conjugated via glucuronidation, sulfonation and glycine conjugation. CA undergoes CYP1A2/2D6/3A4 hydroxylation to active metabolites (cinnamyl alcohol, cinnamic acid) and a reactive epoxide that can be detoxified by epoxide hydrolase. Both are further conjugated by UGTs, sulfotransferases and GSTs. Plasma clearance is moderate (CGA 11.1 mL min⁻¹ kg⁻¹; CA 3.3 mL min⁻¹ kg⁻¹) with short half-lives (CGA 1.4 h; CA 2.8 h), suggesting low accumulation and the need for repeated dosing.