Arzneimittel-Forschung 1988-08-01

[The binding of oxicam derivatives to human serum albumin].

A Kinawi, D Siebler

Index: Arzneimittelforschung 38(8) , 1089-92, (1988)

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Abstract

The binding characteristics of several oxicam derivatives (tenoxicam, 4-hydroxy-2-methyl-N-phenyl-2H-1,2-benzothiazixine-3- carboxamide-1,1-dioxide (CP 14,304), 4-hydroxy-2-methyl-N-2-(3-methyl)-pyridyl-2H-1,2-benzothiazixine-3 -carboxamide- 1,1-dioxide (CP 16,460), piroxicam, meloxicam [corrected], isoxicam, 5-hydroxy-piroxicam) to 2% and 4% human serum albumin (HSA) were determined using a modified ultrafiltration process. The binding properties to HSA were characterized by determining the overall binding constant, the apparent binding constant, the slope, the free reaction energy, and the unbound portion of the drug. The following results were obtained: 1. These oxicam derivatives show a high affinity to HSA. The unbound fraction amounts to 1-3%. 2. The affinity of the compounds to HSA decreases in the order mentioned above. 3. Doubling of the HSA concentration reduces the unbound fraction, to the half, with piroxicam being the only exception.