Turkiye Klinikleri Journal of Biostatistics

.: ORIGINAL RESEARCH
Meta-analysis for Favipiravir Bioequivalence Studies
Favipiravir Biyoeşdeğerlik Çalışmaları İçin Metaanalizi
Emel DOĞAN KURTOĞLUa, Onursal SAĞLAMa
aNovagenix Bioanalytical Drug R&D Centre, Ankara, TURKEY
Turkiye Klinikleri J Biostat. 2021;13(2):170-7
doi: 10.5336/biostatic.2021-82031
Article Language: EN
Full Text
ABSTRACT
 Objective: A global pandemic called coronavirus disease-2019 (COVID-19) has devastatingly hit the world since December 2019. Favipiravir has widely been used in treatment of COVID-19 and generic pharmaceutical companies took an action to manufacture generic drugs of favipiravir. In favipiravir treatment, when the patient needs to switch from one generic drug to another generic drug, the interchangeability of the generic drugs becomes important. For this purpose, meta-analysis is used between generic drugs based on data obtained from independent favipiravir bioequivalence studies. Material and Methods: Pharmacokinetics data of 6 favipiravir bioequivalence studies performed by Novagenix Bioanalytical R&D Centre in Turkey in 2020 were used. The 90% confidence intervals for the differences between the means of pharmacokinetic parameters, area under the curve (AUC0-tlast) and maximum plasma concentration (Cmax), were determined for each binary combinations of six generic drugs by meta-analysis used in average bioequivalence. These confidence intervals are compared with the bioequivalence acceptance limit of 80.00-125.00%. Results: Considering the 90% confidence intervals, 33.33% of the binary combinations of six generic drugs for only Cmax and 53.33% of the binary combinations of six generic drugs for only AUC0-tlast have been concluded as bioequivalent. Three of the binary combinations fulfilled the bioequivalence criteria for both Cmax and AUC0- tlast. Conclusion: When assessing the interchangeability between generic drugs, some of the combinations did not meet the acceptance criteria. Therefore, when a patient switches between favipiravir generic drugs, the pharmacokinetic behaviour of the drug product and thus its efficacy may change.

Keywords: Meta-analysis; bioequivalence; favipiravir; generic drug
ÖZET
 Amaç: Koronavirüs hastalığı-2019 [coronavirus disease2019 (COVID-19)] adlı küresel bir salgın, Aralık 2019'dan beri dünyayı yıkıcı bir şekilde etkiledi. Favipiravir, COVID-19'un tedavisinde yaygın olarak kullanılmakta olup; jenerik ilaç şirketleri, jenerik favipiravir üretmek için harekete geçti. Favipiravir tedavisinde hasta, bir jenerik ilaçtan başka bir jenerik ilaca geçiş yapması gerektiğinde jenerik ilaçların değiştirilebilirliği önem kazanır. Bu amaçla bağımsız favipiravir biyoeşdeğerlik çalışmalarından elde edilen verilere dayalı olarak jenerik ilaçlar arasında metaanalizi kullanılmaktadır. Gereç ve Yöntemler: Novagenix Biyoanalitik Ar-Ge Merkezi tarafından 2020 yılında yapılan 6 favipiravir biyoeşdeğerlik çalışmalarının farmakokinetik verileri kullanılmıştır. Ortalama biyoeşdeğerlikte kullanılan metaanaliz ile 6 jenerik ilacın 2'li kombinasyonlarının farmakokinetik parametreleri için eğri altındaki alan (EAA) ve maksimum plazma konsantrasyon (Cmaks), ortalamalar arasındaki fark için %90 güven aralıkları elde edilmiştir. Bu güven aralıkları, %80,00-125,00 biyoeşdeğerlik kabul limitleri ile karşılaştırılmıştır. Bulgular: Yüzde 90 güven aralıkları dikkate alındığında, yalnızca Cmaks için 6 jenerik ilacın 2'li kombinasyonlarının %33,33'ü ve sadece EAA0-tlast için 6 jenerik ilacın 2'li kombinasyonlarının %53,33'ü biyoeşdeğer olarak sonuçlanmıştır. İkili kombinasyonların 3'ü, hem Cmaks hem de EAA0-tlast için biyoeşdeğerlik kriterlerini karşıladı. Sonuç: Jenerik ilaçlar arasındaki değiştirilebilirliği değerlendirirken, bazı kombinasyonların kabul kriterini sağlamadığı görülmüştür. Bu nedenle, bir hasta favipiravir jenerik ilaçlar arasında geçiş yaptığında, ilaç ürününün farmakokinetik davranışı ve dolayısıyla etkinliği değişebilir.

Anahtar Kelimeler: Metaanalizi; biyoeşdeğerlik; favipiravir; jenerik ilaç
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