生物等效性和生物利用度杂志

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Bioequivalence Study of Molnupiravir 200 mg Capsules in Healthy Thai Volunteers

Vipada Khaowroongrueng, Jaturavit Vattanarongkup, Sumete Kunsa-ngiem, Wiwat Supasena, Lalinthip Saeaue, Busarat Karachot, Piengthong Narakorn, Isariya Techatanawat, Porranee Puranajoti

The antivirals inhibiting RNA-Dependent RNA Polymerase (RdRp) enzyme seem to be the most effective therapeutic solution for a Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). Molnupiravir is a prodrug of N-Hydroxycytidine (NHC) which is subsequently phosphorylated to NHC triphosphate, thereby targeting RdRp and inducing error catastrophe. In response to the treatment demands within the national public health system during the COVID-19 pandemic, the Government Pharmaceutical Organization (GPO), Thailand had developed a generic product of molnupiravir 200 mg capsules. An open label, randomized, two-treatment, two-period, two-sequence, single oral-dose, crossover study was designed to determine the bioequivalence of two molnupiravir 200 mg capsule formulations, MONOVIR® and LAGEVRIO® under fasting conditions. The plasma-concentration time profiles of NHC were used to characterize the rate and extent of absorption of molnupiravir as the parent compound was rapidly converted in plasma. The pharmacokinetics parameters were calculated using non-compartmental model. The 90% confidence intervals of geometric least squares mean ratio (test/reference) for ln-transformed parameters were within 80.00%-125.00% of bioequivalence criteria: 103.74-111.46% for AUC_0-tlast, 103.73%-111.4% for AUC_{0- ∞} and 101.98%-110.19% for C_max. Both products were well tolerated and no serious adverse events were reported. This study demonstrated bioequivalence between MONOVIR® and LAGEVRIO® supporting the interchangeability between these products.