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Article History
Submitted: 22 May 2015
Revised: 18 Sep 2016
Accepted: 07 Nov 2016
First published online: 22 Dec 2016

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Adv Pharm Bull. 2016;6(4):589-595 doi: 10.15171/apb.2016.073

Characterization of the Effect of Drug-Drug Interaction on Protein Binding in Concurrent Administration of Sulfamethoxazol and Diclofenac Sodium Using Bovine Serum Albumin

Research Article

Md Kamal Hossain 1,2, Amina Khatun 1,3 * , Mahmudur Rahman 1,3, Md Nahid Akter 1, Sadia Afreen Chowdhury 4, SM Mahbubul Alam 1,5

1 Laboratory of Pharmaceutical Technology, Pharmacy Discipline, Khulna University, Khulna-9208, Bangladesh.
2 Opsonin Pharma Limited, 30, New Eskaton Road, Dhaka-1000, Bangladesh.
3 Southern Cross University, Lismore, NSW- 2480, Australia.
4 Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Dhaka, Dhaka-1000, Bangladesh.
5 Chancery, High Commission for the People’s Republic of Bangladesh, London.



Abstract
Purpose: This project was aimed to determine the effect of concurrent administration of sulfamethoxazole and diclofenac sodium. Methods: Equilibrium dialysis method was adopted to study different protein binding aspects of sulfamethoxazole and diclofenac sodium. Results: Sulfamethoxazole showed two types of association constants; high affinity constant 29.0±0.20×106 M-1 with lower number of binding sites of 0.7±1 and low affinity constant 1.13±0.20×106 M-1 with higher number of binding sites of 3.45±1 at pH 7.4 and 40 °C temperature. Diclofenac sodium showed high affinity constant 33.66±0.20×106 M-1 with lower number of binding sites of 1.01±1 and low affinity constant 1.72±0.20×106 M-1 with higher number of binding sites of 6.40±1 at the same condition. Site specific probe displacement data implied that site-I, warfarin sodium site, was the high affinity site, while site-II, diazepam site, was the low affinity site for these drugs. During concurrent administration, sulfamethoxazole increased the free concentration of diclofenac sodium from 17.5±0.14% to 70.0±0.014% in absence and from 22.5±0.07% to 83.0±0.014% in presence of site-I specific probe. Diclofenac sodium also increased the free concentration of sulfamethoxazole from 2.8±0.07% to 52.0±0.14% and from 8.5±0.014% to 64.4±0.07% in absence and presence of site-I specific probe respectively. Conclusions: The study revealed that the concurrent administration of sulfamethoxazole and diclofenac sodium may result drug concentration alteration in blood.





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