Competitive binding of ibuprofen and naproxen to bovine serum albumin : modified form of drug-drug displacement interaction at the binding site.
The competitive binding characteristics of ibuprofen and naproxen with respect to binding site on bovine serum albumin (BSA) was studied by equilibrium dialysis method at pH 7.4 and 25 degrees C. We studied the effect of one drug on the free concentration of another in vitro during concurrent administration. There was remarkable increase in free concentration of naproxen when ibuprofen (2x10(-5) M) was added to a 1:1 naproxen-BSA mixture (2x10(-5) M: 2x10(-5) M), suggesting that ibuprofen displaced naproxen from its binding sites. However free fraction of naproxen was not increased up to the level expected from direct competitive displacement. Free concentration of ibuprofen was hardly increased by naproxen when naproxen (2x10(-5) M) was added to the ibuprofen-BSA (1:1) mixture. But in both cases, in presence of ranitidine (site I specific probe), the free concentration of the displaced drug increased more prominently compared to that in absence of ranitidine. This result suggests that, ibuprofen displaces naproxen and vice versa from its high affinity binding site (site II) and the displaced drug rebounds to its low affinity binding site (site I) on BSA molecule. This form of modified displacement has been arbitrarily referred to as site-to-site displacement.
Rahman
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Pharmacy Discipline, Life Science School, Khulna University, Khulna-9208, Bangladesh.
Rahman
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MH
Rahman
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D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry*; D001665:Binding Sites; D001667:Binding, Competitive; D002417:Cattle; D004347:Drug Interactions; D007052:Ibuprofen / Q000737:chemistry*; D009288:Naproxen / Q000737:chemistry*; D012709:Serum Albumin / Q000737:chemistry*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D012709:Serum Albumin; D009288:Naproxen; D007052:Ibuprofen