| Research Article |
Open Access |
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| Evaluation of Bioequivalence and Cardio-Hepatic Safety of
a Single Dose of Fixed Dose Combination of Artemether and
Lumefantrine |
| Suhas Sahebrao Khandave1*, Santosh Shrikrishna Joshi2, Satish Vitthal Sawant1 and Shahoo Vasant Onkar1 |
1Accutest Research Laboratories Limited, A-31, TTC Industrial Area, Khairne MIDC, Navi Mumbai- 400709, Maharashtra, India
2Sequel Pharmchem Pvt Limited, Factory: N-46 MIDC, Anand Nagar, Ambernath, Thane- 421504, Maharashtra, India |
| *Corresponding author: |
Dr. Suhas Sahebrao Khandave
Accutest Research Laboratories Limited
A-31, TTC Industrial Area
Khairne MIDC, Navi Mumbai-
400709
Maharashtra, India
Tel: 91-22-27780718/19/20
Fax: 91-22-27780721
E-mail: suhas.khandave@accutestindia.com |
|
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| Received June 07, 2010; Accepted July 01, 2010; Published July 01, 2010 |
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| Citation: Khandave SS, Joshi SS, Sawant SV, Onkar SV (2010) Evaluation of
Bioequivalence and Cardio-Hepatic Safety of a Single Dose of Fixed Dose
Combination of Artemether and Lumefantrine. J Bioequiv Availab 2: 081-085.
doi:10.4172/jbb.1000036 |
| |
| Copyright: © 2010 Khandave SS, et al. This is an open-access article distributed
under the terms of the Creative Commons Attribution License, which permits
unrestricted use, distribution, and reproduction in any medium, provided the
original author and source are credited. |
| |
| Abstract |
| Background and objective: The existing fixed-dose combination, Coartem® (artemether 20 mg and lumefantrine
80 mg) requires 4 tablets per dose and a total of 24 tablets for the six-dose regimen for the treatment of uncomplicated
P. falciparum malaria compromising the patient compliance. Also, the cardiotoxicity due to lumefantrine because of its
structural similarity with halofantrine remains a matter of debate in therapeutics. |
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| To enhance the patient compliance, the fixed-dose combination of artemether/lumefantrine (80/480 mg) is formulated
by Sequel Pharmachem Pvt. Ltd. India. In the present study, this fixed dose combination (test product) was evaluated
for its bioequivalence to the reference product, Coartem® 20/120 mg (artemether 20 mg and lumefantrine 120 mg) of Novartis Pharma Ltd. with assessment of cardio-hepatic safety. |
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| Methods: A randomized, open label, two-treatment, two-period, two-sequence, single-dose, crossover
bioequivalence study with comparative safety evaluation was conducted on 72 healthy Indian human subjects under
a fed condition. Quantification of artemether, dihydroartemisinin, and lumefantrine was done by a validated LC-MS/
MS method. For bioequivalence, AUC0-240, AUC0-inf and Cmax for artemether and lumefantrine were considered. Safety
assessment was done by monitoring vital signs, QTc interval, serum ALT and AST values before and after treatment.
Max QTc, baseline-corrected QTcmax, AST and ALT values were considered for statistical comparison between the two
treatments. Drug plasma concentrations estimated at identical time points with the ECG recordings were correlated with
ECG parameters. |
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Results: The test product was bioequivalent to the reference product as per the standard bioequivalence criteria.
There was no clinically significant difference between the two treatments for all the safety parameters. No significant
observation suggestive of cardiotoxicity and hepatotoxicity was noted in this study.
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| Conclusion: The test product can be used as a therapeutic option with likely better patient compliance in the
treatment of uncomplicated P. falciparum malaria. |
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