Blood Distribution of Tenoxicam in Humans: A Particular Hsa Drug Interaction

Abstract

Blood binding of tenoxicam was studied in vitro by equilibrium dialysis. Isolated human plasma proteins and blood cells were checked, and the distribution of the bound form was then calculated. The results showed that tenoxicam is mainly bound to HSA and that binding percentages are not different when measured in plasma (98.4%) and in an HSA solution at physiological concentration (704 microM, 98.15%). In these conditions, within the range of 1-150 microM, the tenoxicam binding percentage remained constant, evidence of a nonsaturable process. When a lower HSA concentration (10 microM) was used, the binding parameters of the tenoxicam interaction were calculated by using the same equilibrium dialysis data, by 3 methods of analysis- a stoichiometric method and site-oriented methods, fixing or not the number of HSA binding sites (n) as integer values. The best fit was observed with the first method, suggesting that two main interactions occurred. The site-oriented method gave lesser fits, the better being observed when n was not fixed. Its value, 1.77, suggest the possibility of two binding sites, one of them not preformed. The effects of known markers of site I, warfarin and apazone, of site II, diazepam and ibuprofen and of palmitic acid showed that tenoxicam is bound simultaneously to both sites I and II. The binding capacity of site I for tenoxicam is enhanced by diazepam: as this compound alone is bound to site II, this result suggests that the two HSA binding sites are not independent.

A method for rapidly predicting drug tissue distribution using surfactant vesicle electrokinetic chromatography

“…Thirdly, previous researchers have reported extensive interaction between some moderateto-strong basic drugs and tissue DNA [44,45], this could cause significantly under-predicting for drug candidates. Finally, some tissue proteins, such as a1-acid glycoprotein, also contribute to tissue affinities, although its impact on the regional distribution of the drug can be considered minimal [46]. Limitations aside, there is still a significant correlation between retention in the AOT vesicle SEKC system and in vivo tissue distribution data, suggesting AOT vesicle SEKC can provide a primary profile screening method for a large number of drug candidates early in the drug discovery process.…”

A re-evaluation of the HSA-piroxicam interaction

“…i.e. isoxicam and tenoxicam which were shown to bind to HSA with a main high affinity site plus another one of a lesser affinity (6,7).…”

“…The equilibrium binding data were fitted according to the site specific model and the stoichiometric one as previously reported (6,7). The binding characteristics were expressed as follows: n is the number of binding sites per mole of protein, N is the binding site concentration, K, is the corresponding association constant, and K the stoichiometric constant.…”

“…The identification of HSA (3,4) but none of them seemed to involve a competitive mechanism (4). Recently we observed that two other oxicams, isoxicam and tenoxicam, bound to both sites with different affinities (6,7) and this property seemed to be characteristic of this chemical group.…”

Human Serum Albumin Conformational Changes as Induced by Tenoxicam and Modified by Simultaneous Diazepam Binding

“…Dialysis was performed with a Dianorm (Science Tec, Les Ulis, France) apparatus at 25 and 15°C as previously described (Bree et al 1989). Equilibrium was where R is the concentration of total protein, n, is the number of binding sites and K, the association constant of the ith class of sites.…”