[Source: Antimicrobial Agents and Chemotherapy, full text: (LINK). Abstract, edited.]
Pharmacokinetics, Metabolism, and Excretion of the Antiviral Drug Arbidol in Humans
Pan Deng 1, Dafang Zhong 1, Kate Yu 2, Yifan Zhang 1, Ting Wang 3 and Xiaoyan Chen 1,*
Author Affiliations: 1Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China 2Waters Corporation, MA, USA 3First Affiliated Hospital of Lanzhou University, Lanzhou, China
Arbidol is a broad-spectrum antiviral drug, which is clinically used to treat influenza. In this study, the pharmacokinetics, metabolism, and excretion of arbidol were investigated in healthy male Chinese volunteers after a single oral administration of 200 mg of arbidol hydrochloride. A total of 33 arbidol metabolites were identified in human plasma, urine, and feces. The principal biotransformation pathways included sulfoxidation, dimethylamine N-demethylation, glucuronidation, and sulfate conjugation. The major drug-related component in the plasma was sulfinylarbidol (M6-1), followed by unmetabolized arbidol, N-demethylsulfinylarbidol (M5), and sulfonylarbidol (M8). The exposures of M5, M6-1, and M8, as determined by the metabolite-to-parent AUC0-t ratio, were 0.9 ± 0.3, 11.5 ± 3.6, and 0.5 ± 0.2, respectively. In human urine, glucuronide and sulfate conjugates were detected as the major metabolites, accounting for 6.3% of the dose excreted within 0 to 96 h after drug administration. The fecal specimens mainly contained the unchanged arbidol, accounting for 32.4% of the dose. Microsomal incubation experiments demonstrated that liver and intestines were the major organs that metabolize arbidol in humans. CYP3A4 was the major isoform involved in arbidol metabolism, whereas the other P450s and FMOs played minor roles. These results indicated possible drug interactions between arbidol and CYP3A4 inhibitors and inducers. Further investigations are needed to understand the importance of M6-1 in the efficacy and safety of arbidol, because of its high plasma exposure and long elimination half-life (25.0 h).
* Corresponding author: Xiaoyan Chen, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 501 Haike Road, Shanghai 201203, China, Phone/Fax: 86-021-50800738, Email: firstname.lastname@example.org
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