The anti-COVID-19 drug nirmatrelvir crosses the blood‒brain barrier and exhibits herb–drug pharmacokinetic interactions with Scutellaria baicalensis formulations
Wan-Hsin Lee,
Yen-Ying Kung,
Chung-Kai Sun,
Chun-Hao Chang,
Wen-Ya Peng,
Lie-Chwen Lin,
Chung-Hua Hsu,
Muh-Hwa Yang,
Tung-Hu Tsai
Affiliations
Wan-Hsin Lee
Institute of Traditional Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
Yen-Ying Kung
Institute of Traditional Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan; Center for Traditional Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
Chung-Kai Sun
Institute of Traditional Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
Chun-Hao Chang
Institute of Traditional Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
Wen-Ya Peng
Institute of Traditional Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
Lie-Chwen Lin
National Research Institute of Chinese Medicine, Ministry of Health and Welfare, Taipei, Taiwan
Chung-Hua Hsu
Institute of Traditional Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan; Branch of Linsen Chinese and Kunming, Taipei City Hospital, Taipei, Taiwan
Muh-Hwa Yang
Institute of Clinical Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
Tung-Hu Tsai
Institute of Traditional Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan; Graduate Institute of Acupuncture Science, China Medical University, Taichung, 404, Taiwan; School of Pharmacy, Kaohsiung Medical University, Kaohsiung, 807, Taiwan; Graduate Institute of Law and Interdisciplinary Studies, College of Law, National Chengchi University, Taipei, 116, Taiwan; Corresponding author. Institute of Traditional Medicine, College of Medicine, National Yang Ming Chiao Tung University, 155, Li-Nong Street Section 2, Taipei, 112, Taiwan.
Aim of the study: Our hypothesis is that nirmatrelvir can penetrate the blood‒brain barrier and reach effective concentrations in the brain. Furthermore, herbal formulations can help maintain nirmatrelvir levels in the body, suggesting potential interactions between these medications. Materials and methods: To investigate this hypothesis, an animal model combining multisite microdialysis, ultrahigh-performance liquid chromatography and tandem mass spectrometry (UHPLC-MS/MS) methods was developed to monitor nirmatrelvir levels in the blood and brain of rats. Results: The pharmacokinetic results showed that the area under the curve (AUC) of nirmatrelvir in the blood and brain was 798.3 ± 58.56 and 187.2 ± 23.46 min μg/mL, respectively, after the administration of nirmatrelvir alone (15 mg/kg, iv). When the Scutellaria baicalensis formulations were administered for five consecutive days prior to drug administration, the AUC of nirmatrelvir in the blood increased. Conclusions: These results provide constructive preclinical information that the concentrations of nirmatrelvir in the blood and brain were greater than the effective concentration (EC90) for more than 6 h, and the Scutellaria baicalensis formulations had synergistic pharmacokinetic effects by increasing the concentration of nirmatrelvir in the blood.
