Pharmacokinetic study of thymol after intravenous injection and high‐dose inhalation in mouse model

Thymol is generally recognized as a safe substance by the FDA and has been widely used in the pharmaceutical, food, and cosmetic industries. Pharmacokinetic (PK) studies of thymol have been previously conducted for oral administration, but there has been no PK study for inhalation administration or intravenous (IV) injection. This study aims at exploring and comparing the inhalation and IV PK profile of thymol in a mouse model. The inhalation PK for mouse model was corrected with fur/skin absorption. Thirty‐two male CD‐1 mice were randomized into two study arms, Arm‐A for intravenous (n = 16) and Arm‐B for inhalation (n = 16). The amount of thymol in the mouse serum was measured for Arm‐A and for Arm‐B at the highest dose. Furthermore, 48 mice were utilized for fur/skin absorption of thymol. In total, 320 mouse serum samples for thymol were analyzed by LC/MS method. After inhalation, the peak concentration of thymol in mouse serum was 42.3 ng/mL (C(max)) and occurred at 2 minutes (t(max)). The AUC of the inhaled thymol at 0‐60 minutes (AUC(0‐60)) was 464 ng/mL/min. From 10‐60 minutes post‐dose, the PK inhalation curve appeared to be higher than that for the IV injection. This is likely attributed to the effect of absorption of thymol through the fur/skin of mice. After an adjustment by fur/skin absorption, the PK profile for net inhalation closely matched the two‐compartment model. In fact, the bioavailability for the net inhalation of thymol was 74% and 77% relative to that for IV injection per AUC(0‐60min) and AUC(0‐infinite), respectively.