Bioequivalence study of two favipiravir tablet formulations in healthy male subjects

Sağlam, Onursal; Güney, Berrak; Saraner, Nihal; Sevici, Gamze; Doğan-Kurtoğlu, Emel; Ulusoy, Merve Gülşah; Demiray, Gökçe; Nacak, Muradiye; Erenmemişoğlu, Aydın; Özbek, Mahmut; Aytac, Peri S.

doi:10.5414/cp203936

Cited by 7 publications

(7 citation statements)

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“…Despite this second run of experiments, the CC 10 could not be obtained for remdesivir, dexamethasone, and favipiravir, as the cytotoxic effect of these compounds was not extensive enough in a relevant concentration range to obtain a sigmoidal curve. In these cases, the maximum plasma concentration (C max ) or 10-fold of the C max was used to ensure a physiologically relevant concentration range [ 27 , 28 , 29 ]. Thereafter, the CC 10 , C max , or C max x10 of each drug ( Table 1 ) was used as a benchmark concentration (BC) to set a working concentration range to be tested—namely, BC-BC/2-BC/10 for protein and mRNA quantification measurements, and BCx10-BCx5-BCx2-BC-BC/2-BC/10 for the assessment of effects on Panx1 channel activity ( Table 1 ).…”

Section: Resultsmentioning

confidence: 99%

Effects of Drugs Formerly Suggested for COVID-19 Repurposing on Pannexin1 Channels

Caufriez

Tabernilla

Campenhout

et al. 2022

IJMS

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Although many efforts have been made to elucidate the pathogenesis of COVID-19, the underlying mechanisms are yet to be fully uncovered. However, it is known that a dysfunctional immune response and the accompanying uncontrollable inflammation lead to troublesome outcomes in COVID-19 patients. Pannexin1 channels are put forward as interesting drug targets for the treatment of COVID-19 due to their key role in inflammation and their link to other viral infections. In the present study, we selected a panel of drugs previously tested in clinical trials as potential candidates for the treatment of COVID-19 early on in the pandemic, including hydroxychloroquine, chloroquine, azithromycin, dexamethasone, ribavirin, remdesivir, favipiravir, lopinavir, and ritonavir. The effect of the drugs on pannexin1 channels was assessed at a functional level by means of measurement of extracellular ATP release. Immunoblot analysis and real-time quantitative reversetranscription polymerase chain reaction analysis were used to study the potential of the drugs to alter pannexin1 protein and mRNA expression levels, respectively. Favipiravir, hydroxychloroquine, lopinavir, and the combination of lopinavir with ritonavir were found to inhibit pannexin1 channel activity without affecting pannexin1 protein or mRNA levels. Thusthree new inhibitors of pannexin1 channels were identified that, though currently not being used anymore for the treatment of COVID-19 patients, could be potential drug candidates for other pannexin1-related diseases.

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Section: Resultsmentioning

confidence: 99%

Effects of Drugs Formerly Suggested for COVID-19 Repurposing on Pannexin1 Channels

Caufriez

Tabernilla

Campenhout

et al. 2022

IJMS

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“…The pharmacokinetic parameters in the present study were slightly higher than those reported in previous studies, which reported mean C max and AUC 0-∞ values in the range of ≈5-6 μg/mL and 10-13 h • μg/mL, respectively, after oral administration of equivalent favipiravir 200-mg doses in healthy subjects under fasting conditions. [21][22][23] The current study had limitations that should be considered. Since data were obtained only from healthy subjects with a limited number of sample sizes, the pharmacokinetic characteristics of favipiravir might not represent the whole population.…”

Section: Discussionmentioning

confidence: 95%

Pharmacokinetic Comparison of Favipiravir Oral Solution and Tablet Formulations in Healthy Thai Volunteers

Siripongboonsitti

Ungtrakul

Watanapokasin

et al. 2022

Clinical Pharm in Drug Dev

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This study compared the pharmacokinetics and safety of favipiravir oral solution with those of tablet formulations, which were agents repurposed to treat nonsevere coronavirus disease 2019 in Thailand. In an open-label, single-dose, randomized, crossover study, 24 healthy subjects under fasting conditions were randomly assigned to a single dose of 200 mg of favipiravir, either as an oral solution of 200 mg/15 mL (test product) or a tablet (reference product), separated by a 7-day washout period. Fifteen plasma samples were collected over 12 hours after drug administration. Plasma favipiravir levels were quantified using in-house developed ultra-high-performance liquid chromatography-tandem mass spectrometry. The test/reference geometric mean ratio along with 90%CI for the maximum plasma concentration, area under the concentration-time curve (AUC) to the time of the last quantifiable concentration,and AUC after single-dose administration, extrapolated to infinity were 115.3% (90%CI, 107.7%-123.3%), 100.4% (90%CI, 96.9%-104.0%), and 100.4% (90%CI, 96.8%-104.2%), respectively. These results were within the predefined acceptance criteria for bioequivalence (80.0%-125.0%). No adverse events were observed in either group. The oral solution formulation could offer the advantage of easier swallowing in broader patient groups.

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“…In another study to evaluate the bioequivalence of two favipiravir oral tablet formulations (200 mg) in Caucasian adult males under fasting conditions, the observed Cp max of the reference product was 5002.171 ± 1231.177 ng/mL and AUC 0-∞ was 10152.115 ± 2507.694 ng.h/mL. T max was 0.75 h while t 1/2 was 1.319 h [34]. The results showed substantial comparisons between Caucasian and Egyptian volunteers.…”

Section: Discussionmentioning

confidence: 99%

Does the Ethnic Difference Affect the Pharmacokinetics of Favipiravir? A Pharmacokinetic Study in Healthy Egyptian Volunteers and Development of Level C In-vitro In-vivo Correlation

2023

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Favipiravir is an antiviral drug used to treat influenza and is also being investigated for the treatment of SARS-CoV-2. Its pharmacokinetic profile varies depending on ethnic group. The present research examines the pharmacokinetic features of favipiravir in healthy male Egyptian volunteers. Another goal of this research is to determine the optimum dissolution testing conditions for immediate release tablets. In vitro dissolution testing was investigated for favipiravir tablets in three different pH media. The pharmacokinetic features of favipiravir were examined in 27 healthy male Egyptian volunteers. The parameter “AUC0-t” vs. percent dissolved was used to develop level C in vitro in vivo correlation (IVIVC) to set the optimum dissolution medium to achieve accurate dissolution profile for favipiravir (IR) tablets. The in vitro release results revealed significant difference among the three different dissolution media. The Pk parameters of twenty-seven human subjects showed mean value of Cpmax of 5966.45 ng/mL at median tmax of 0.75 h with AUC0-∞ equals 13325.54 ng.h/mL, showing half-life of 1.25 h. Level C IVIVC was developed successfully. It was concluded that Egyptian volunteers had comparable Pk values to American and Caucasian volunteers, however they were considerably different from Japanese subjects. AUC0-t vs. % dissolved was used to develop level C IVIVC to set the optimum dissolution medium. Phosphate buffer medium (pH 6.8) was found to be the optimum dissolution medium for in vitro dissolution testing for Favipiravir IR tablets.

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Bioequivalence study of two favipiravir tablet formulations in healthy male subjects

Cited by 7 publications

References 0 publications

Effects of Drugs Formerly Suggested for COVID-19 Repurposing on Pannexin1 Channels

Effects of Drugs Formerly Suggested for COVID-19 Repurposing on Pannexin1 Channels

Pharmacokinetic Comparison of Favipiravir Oral Solution and Tablet Formulations in Healthy Thai Volunteers

Does the Ethnic Difference Affect the Pharmacokinetics of Favipiravir? A Pharmacokinetic Study in Healthy Egyptian Volunteers and Development of Level C In-vitro In-vivo Correlation

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