Amphastar New Drug Research Center (NDRC) Chino California USA.
Division of Pulmonary and Critical Care edicine, David Geffen School of Medicine University of California at Los Angeles Los Angeles California USA.
Pharmacol Res Perspect. 2019 Aug 19;7(5):e00515. doi: 10.1002/prp2.515. eCollection 2019 Oct.
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 ( ) and occurred at 2 minutes ( ). The AUC of the inhaled thymol at 0-60 minutes (AUC) 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 and AUC, respectively.
百里酚通常被 FDA 认定为安全物质，已广泛应用于制药、食品和化妆品行业。此前已进行了百里酚口服给药的药代动力学 (PK) 研究，但尚未进行吸入给药或静脉 (IV) 注射的 PK 研究。本研究旨在探索和比较百里酚在小鼠模型中的吸入和 IV PK 特征。通过毛皮/皮肤吸收对小鼠模型的吸入 PK 进行了校正。将 32 只雄性 CD-1 小鼠随机分为静脉注射组（n=16）和吸入组（n=16）。在最高剂量下，测定了 Arm-A 中血清中百里酚的含量，以及 Arm-B 中血清中百里酚的含量。还利用 48 只小鼠进行了百里酚的毛皮/皮肤吸收。共分析了 320 个小鼠血清样本中的百里酚，采用 LC/MS 方法。吸入后，小鼠血清中百里酚的峰浓度为 42.3ng/mL（），出现在 2 分钟（）。0-60 分钟（AUC）的吸入百里酚 AUC 为 464ng/mL/min。从 10-60 分钟给药后，PK 吸入曲线似乎高于 IV 注射。这可能归因于通过小鼠的毛皮/皮肤吸收百里酚的作用。通过毛皮/皮肤吸收校正后，净吸入 PK 曲线与双室模型吻合。实际上，相对于 AUC 和 AUC，净吸入百里酚的生物利用度分别为 IV 注射的 74%和 77%。
