Randomized, open-label, two-way crossover bioequivalence study of Novirax (Drug International Ltd, Bangladesh) compared with Zovirax (Glaxo Wellcome, UK) – two brands of Acyclovir – in healthy male volunteers

Authors

  • Uttam Kumar Sarker Department of Chemistry, Hajee Mohammad Danesh Science and Technology University, Dinajpur, Bangladesh
  • Mezbah Hossain Department of Chemistry, Hajee Mohammad Danesh Science and Technology University, Dinajpur, Bangladesh
  • Md. Atikul Islam Department of Chemistry, Hajee Mohammad Danesh Science and Technology University, Dinajpur, Bangladesh
  • Md. Shamsuzzoha Department of Chemistry, Hajee Mohammad Danesh Science and Technology University, Dinajpur, Bangladesh
  • Md. Najim Uddin Department of Chemistry, Hajee Mohammad Danesh Science and Technology University, Dinajpur, Bangladesh
  • Mir Misbahuddin Department of Pharmacology, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh
  • Md. Elias Mollah Department of Chemistry, Jahangirnagar University, Savar, Dhaka, Bangladesh.
  • Md. Rabiul Islam Department of Chemistry, Jahangirnagar University, Savar, Dhaka, Bangladesh.

DOI:

https://doi.org/10.22270/ajprd.v9i3.964

Keywords:

Bioequivalence, Acyclovir, HPLC, Pharmacokinetics, Drug International Ltd.

Abstract

Objectives: A crossover-randomized bioequivalence study of two oral formulations of acyclovir 200 mg tablet was accomplished with 16 adults and physically fit male volunteers from Bangladesh. NOVIRAX™ (Drug International Ltd, Bangladesh) was the test variant whereas ZOVIRAX™ (GlaxoWellcome) was the reference one.

Methods: After a night fasting each volunteer was subjected to take a single dosage of tablet with 150 mL of water. After a week for complete washing out, a second dosage was applied. After that, blood samples were collected at a serial interval for a 24 hours period to observe the plasma concentration by HPLC technique. Several pharmacokinetic parameters like Cmax, Tmax, AUC0→24h, t1/2, and Kel were estimated.

Results: The mean (± SD) AUC0→24h for acyclovir of test variant NOVIRAXTM for 16 participants was 1057.5 ± 358.9 ng/hr/mL whereas it was 1134.9 ± 467.2 ng/hr/mL for acyclovir of ZOVIRAXTM. The relative bioavailability (NOVIRAXTM/ZOVIRAXTM ratio) was 93.2%. The Cmax, tmax, half-life of elimination (t1/2) and the rate of elimination (Kel) of acyclovir of test drug were 207.0 ± 86.9 ng/mL, 2.4 ± 0.4 hours, 3.2 ± 1.8 hour and 0.0898 respectively. The Cmax, tmax, half-life of elimination (t1/2) and the rate of elimination (Kel) of acyclovir of reference drug were 230.7 ± 107.2 ng/mL, 2.0 ± 0.9 hours, 2.8 ± 1.2 hour and 0.0921 respectively.

Conclusion: Depend on these statistical speculations; it was culminated that a NOVIRAX tablet is bioequivalent to a ZOVIRAX tablet.

 

Downloads

Download data is not yet available.

Author Biographies

Uttam Kumar Sarker, Department of Chemistry, Hajee Mohammad Danesh Science and Technology University, Dinajpur, Bangladesh

Department of Chemistry, Hajee Mohammad Danesh Science and Technology University, Dinajpur, Bangladesh

Mezbah Hossain, Department of Chemistry, Hajee Mohammad Danesh Science and Technology University, Dinajpur, Bangladesh

Department of Chemistry, Hajee Mohammad Danesh Science and Technology University, Dinajpur, Bangladesh

Md. Atikul Islam, Department of Chemistry, Hajee Mohammad Danesh Science and Technology University, Dinajpur, Bangladesh

Department of Chemistry, Hajee Mohammad Danesh Science and Technology University, Dinajpur, Bangladesh

Md. Shamsuzzoha, Department of Chemistry, Hajee Mohammad Danesh Science and Technology University, Dinajpur, Bangladesh

Department of Chemistry, Hajee Mohammad Danesh Science and Technology University, Dinajpur,Bangladesh

Md. Najim Uddin, Department of Chemistry, Hajee Mohammad Danesh Science and Technology University, Dinajpur, Bangladesh

Department of Chemistry, Hajee Mohammad Danesh Science and Technology University, Dinajpur, Bangladesh

Mir Misbahuddin, Department of Pharmacology, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh

Department of Pharmacology, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh

Md. Elias Mollah, Department of Chemistry, Jahangirnagar University, Savar, Dhaka, Bangladesh.

Department of Chemistry, Jahangirnagar University, Savar, Dhaka, Bangladesh.

Md. Rabiul Islam, Department of Chemistry, Jahangirnagar University, Savar, Dhaka, Bangladesh.

Department of Chemistry, Jahangirnagar University, Savar, Dhaka, Bangladesh.

References

1. De Clercq E, Field HJ. Antiviral prodrugs–the development of successful prodrug strategies for antiviral chemotherapy. British journal of pharmacology. 2006; 147(1):1-1.
2. Hammer KD, Dietz J, Lo TS, Johnson EM. A systematic review on the efficacy of topical acyclovir, penciclovir, and docosanol for the treatment of herpes simplex labialis. Dermatology. 2018; 6(1):118-123
3. Rafailidis PI, Mavros MN, Kapaskelis A, Falagas ME. Antiviral treatment for severe EBV infections in apparently immunocompetent patients. Journal of clinical virology. 2010; 49(3):151-7.
4. The American Society of Health-System Pharmacists. Archived from the original on 2015-01-05. Retrieved Jan 1, 2015.
5. Gershburg E, Pagano JS. Epstein–Barr virus infections: prospects for treatment. Journal of Antimicrobial Chemotherapy. 2005 Aug 1; 56(2):277-81.
6. Ganesan A, Proudfoot J. Analogue-based drug discovery. Fischer J, Ganellin CR, editors. Mörlenbach, Germany: Wiley-VCH; 2010
7. Wilhelmus KR. Antiviral treatment and other therapeutic interventions for herpes simplex virus epithelial keratitis. Cochrane Database of Systematic Reviews. 2015.
8. Hamilton RJ. Tarascon Pocket Pharmacopoeia 2017 Deluxe Lab-Coat Edition. Jones & Bartlett Learning; 2016.
9. Mar 10, 2015. Archived from the original on 5 March 2016. Retrieved 8 March 2016. Even with the highest maternal dosages, the dosage of acyclovir in milk is only about 1% of a typical infant dosage and would not be expected to cause any adverse effects in breastfed infants
10. Gartner LM, Morton J, Lawrence RA, Naylor AJ, O'Hare D, Schanler RJ, Eidelman AI. Breastfeeding and the use of human milk. Pediatrics. 2005; 115(2):496-506.
11. "Prescribing medicines in pregnancy database". Australian Government. 3 March 2014. Archived from the original on 8 April 2014. Retrieved 22 April 2014.
12. Rossi, S, ed. (2013). Australian Medicines Handbook (2013ed.). Adelaide: The Australian Medicines Handbook Unit Trust. ISBN 978-0-9805790-9-3.
13. Pottage JC, Kessler HA, Goodrich JM, Chase R, Benson CA, Kapell K, Levin S. In vitro activity of ketoconazole against herpes simplex virus. Antimicrobial agents and chemotherapy. 1986; 30(2):215-9.
14. XIAO-YING LIAO, QIANG-QIANG DENG, LI HAN, ZHI-TAO WU, ZHAO-LIANG PENG, YUAN XIE, GUANG-JI WANG, JI-YE AA, AND GUO-YU PAN, LEFLUNOMIDE INCREASED THE RENAL EXPOSURE OF ACYCLOVIR BY INHIBITING OAT1/3 AND MRP2,ACTA PHARMACOL SIN. 2020; 41(1): 129–137
15. GlaxoSmithKline Zovirax® (acyclovir sodium) for injection prescribing information. Research Triangle Park, NC; 2003 Nov
16. Shah VP, Midha KK, Dighe S, McGilveray IJ, Skelly JP, Yacobi A, Layloff T, Viswanathan CQ, Cook CE, McDowall RD. Analytical methods validation: bioavailability, bioequivalence and pharmacokinetic studies. Conference report. European journal of drug metabolism and pharmacokinetics. 1991;16(4):249-55.
17. Kinetica TM2000. Version 3.0, Innaphase, User Manual, 1999.
18. FDA F. Guidance for industry: bioanalytical method validation. http://www. fda. gov/cder/Guidance/4252fnl. pdf. 2001.
19. Peace KE, editor. Biopharmaceutical statistics for drug development. Marcel Dekker, Incorporated; 1988.

Published

2021-06-15

How to Cite

Sarker, U. K., Hossain, M., Islam, M. A., Shamsuzzoha, M., Najim Uddin, M., Misbahuddin, M., … Islam, M. R. (2021). Randomized, open-label, two-way crossover bioequivalence study of Novirax (Drug International Ltd, Bangladesh) compared with Zovirax (Glaxo Wellcome, UK) – two brands of Acyclovir – in healthy male volunteers. Asian Journal of Pharmaceutical Research and Development, 9(3), 6–10. https://doi.org/10.22270/ajprd.v9i3.964