J Pharm Biomed Anal
Institute of Traditional Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei 112, Taiwan; Graduate Institute of Acupuncture Science, China Medical University, Taichung 404, Taiwan; Department of Chemistry, National Sun Yat-Sen University, Kaohsiung 804, Taiwan; School of Traditional Chinese Medicine, Chang Gung University, Taoyuan City 333, Taiwan. Electronic address:
Published: September 2023
The aim of this study was to explore the effects of herbal drug pharmacokinetic interactions on the biotransformation of molnupiravir and its metabolite β-D-N4-hydroxycytidine (NHC) in the blood and brain. To investigate the biotransformation mechanism, a carboxylesterase inhibitor, bis(4-nitrophenyl)phosphate (BNPP), was administered. Not only molnupiravir but also the herbal medicine Scutellaria formula-NRICM101 is potentially affected by coadministration with molnupiravir. However, the herb-drug interaction between molnupiravir and the Scutellaria formula-NRICM101 has not yet been investigated. We hypothesized that the complex bioactive herbal ingredients in the extract of the Scutellaria formula-NRICM101, the biotransformation and penetration of the bloodbrain barrier of molnupiravir are altered by inhibition of carboxylesterase. To monitor the analytes, ultrahigh-performance liquid chromatography tandem mass spectrometry (UHPLCMS/MS) coupled with the microdialysis method was developed. Based on the dose transfer from humans to rats, a dose of molnupiravir (100 mg/kg, i.v.), molnupiravir (100 mg/kg, i.v.) + BNPP (50 mg/kg, i.v.), and molnupiravir (100 mg/kg, i.v.) + the Scutellaria formula-NRICM101 extract (1.27 g/kg, per day, for 5 consecutive days) were administered. The results showed that molnupiravir was rapidly metabolized to NHC and penetrated into the brain striatum. However, when concomitant with BNPP, NHC was suppressed, and molnupiravir was enhanced. The blood-to-brain penetration ratios were 2% and 6%, respectively. In summary, the extract of the Scutellaria formula-NRICM101 provides a pharmacological effect similar to that of the carboxylesterase inhibitor to suppress NHC in the blood, and the brain penetration ratio was increased, but the concentration is also higher than the effective concentration in the blood and brain.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10228170 | PMC |
http://dx.doi.org/10.1016/j.jpba.2023.115499 | DOI Listing |
J Pharm Biomed Anal
September 2023
Institute of Traditional Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei 112, Taiwan; Graduate Institute of Acupuncture Science, China Medical University, Taichung 404, Taiwan; Department of Chemistry, National Sun Yat-Sen University, Kaohsiung 804, Taiwan; School of Traditional Chinese Medicine, Chang Gung University, Taoyuan City 333, Taiwan. Electronic address:
The aim of this study was to explore the effects of herbal drug pharmacokinetic interactions on the biotransformation of molnupiravir and its metabolite β-D-N4-hydroxycytidine (NHC) in the blood and brain. To investigate the biotransformation mechanism, a carboxylesterase inhibitor, bis(4-nitrophenyl)phosphate (BNPP), was administered. Not only molnupiravir but also the herbal medicine Scutellaria formula-NRICM101 is potentially affected by coadministration with molnupiravir.
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