Randomized two way crossover open label study to compare the bioequivalence of LOSARDIL 100 TM (Drug International Ltd, Bangladesh) and COZAAR TM (Merck Sharp & Dhome Ltd, UK) in Bangladeshi normal male volunteers

Authors

  • Uttam Kumar Sarker Department of Chemistry, Hajee Mohammad Danesh Science and Technology University, Dinajpur
  • Fatiha Farhana Department of Chemistry, Hajee Mohammad Danesh Science and Technology University, Dinajpur, Bangladesh
  • Atikul Islam Department of Chemistry, Hajee Mohammad Danesh Science and Technology University, Dinajpur, Bangladesh
  • Mir Misbahuddin Department of Pharmacology, Bangabandhu Sheikh Mujib Medical University, Dhaka
  • Md. Rabiul Islam Department of Chemistry, Jahangirnagar University, Savar, Dhaka, Bangladesh.

DOI:

https://doi.org/10.22270/ajprd.v11i1.1228

Keywords:

Bioequivalence, Losartan potassium, Hypertension, HPLC, Pharmacokinetics, Drug International Ltd.

Abstract

Objectives: A crossover-randomized bioequivalence study of two oral formulations of losartan (100 mg) tablets was carried out in 16 healthy male Bangladeshi volunteers. The test and reference formulations were LOSARDIL 100™ (Drug International Ltd, Bangladesh) and COZAAR™ (Merck Sharp & Dohme Ltd, UK), respectively.

Methods: Each tablet was administered with 150 mL of water to subjects after whole night fasting condition on two therapy days distinct by 1 week washout period. After administration, blood samples were accumulated periodically for 24 hours. The plasma concentrations of losartan were evaluated using a validated HPLC method. The pharmacokinetic parameters Cmax, Tmax, AUC0→24h, t1/2, and Kel were determined.

Results: The mean (± SD) AUC0→24h for losartan of test drug LOSARDIL 100TM for 16 volunteers was 3310 ± 1165 ng.hr/mL whereas it was 3545 ± 1251 ng.hr/mL for losartan of COZAARTM . The relative bioavailability (LOSARDIL 100TM/COZAARTM ratio) was 93%. The Cmax, tmax, half-life of elimination (t1/2) and the rate of elimination (Kel) of losartan of test drug were 1855 ± 675 ng/mL, 0.77 ± 0.39 hours, 4.69 ± 1.17 hour and 0.15 ± 0.04 respectively. The Cmax, tmax, half-life of elimination (t1/2) and the rate of elimination (Kel) of losartan of reference drug were 2254 ± 944 ng/mL, 0.87 ± 0.29 hours, 4.13 ± 1.41  hour and 0.20 ± 0.04 respectively.  

Conclusion: Depend on the statistical interpretation the 90% CI for the test and reference drugs were observed within the acceptance range of 80-125%. In conjecture, LOSARDIL 100™ is bioequivalent to COZAAR ™ in terms of absorption.

 

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Author Biographies

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

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

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

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

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

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

Department of Pharmacology, Bangabandhu Sheikh Mujib Medical University, Dhaka

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

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

References

1. Whitworth JA, World Health Organization, International Society of Hypertension Writing Group. WHO/ISH Statement on management of Hypertension. J Hypertens 2003;21:1983-92
2. Losartan Potassium Tablet Prescribing information. Lupin Pharmaceuticals, Inc. Revised: 02/2011 Available from: http://www.dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=e5886220-43b7-46e1-9034-5242ba245bd1).[Last revised on 2011 Feb 28]
3. Michael W. Clinical Safety and Tolerability of Losartan. Clin Ther 1977; 4:604-16.
4. Aghera NJ, Shah SD, Vadalia KR. Formulation and Evaluation of Sublingual Tablets of Losartan Potassium. Asian Pacific J Tropical Disease 2012; 2:S130-5.
5. Koytcheva R, Ozalpb Y, Erenmemisogluc A, Van der Meerd MJ, Alpanb RS. Combination of Losartan and Hydrochlorothiazide: In vivo Bioequivalence. Arzneimittelforschung 2004;54:611-7
6. Center for Drug Evaluation and Research (2003). "Guidance for Industry: Bioavailability and Bioequivalence Studies for Orally Administered Drug Products — General Considerations" (PDF). United States Food and Drug Administration.
7. Midha KK, McKay G. Bioequivalence; Its History, Practice, and Future. AAPS J 2009; 11:664-70.
8. Shah VP, Midha KK, Dighe S, et al. Conference report: Analytical method validation: Bioavailability, bioequivalence and pharmacokinetic studies. Eur J Drug Metab Pharmacokinet 1991; 16: 249–255.
9. Kinetica TM2000. Version 3.0, Innaphase, User Manual, 1999.
10. Uesugi T. FDA. Bioanalytical method validation. Food and drug administration. Guidance for Industry. 2001:1–22;
11. Westlake WJ. Bioavailability, bioequivalence of pharmaceutical formulations. In Biopharmaceutical Statistics for Drug Development, Peace KE (ed.). Marcel Dekker: New
12. York, 1988; 329–352.

Published

2023-02-15

How to Cite

Sarker, U. K., Farhana, F., Islam, A., Misbahuddin, M., & Islam, M. R. (2023). Randomized two way crossover open label study to compare the bioequivalence of LOSARDIL 100 TM (Drug International Ltd, Bangladesh) and COZAAR TM (Merck Sharp & Dhome Ltd, UK) in Bangladeshi normal male volunteers. Asian Journal of Pharmaceutical Research and Development, 11(1), 8–13. https://doi.org/10.22270/ajprd.v11i1.1228