Selective Binding of Tamsulosin to Genetic Variants of Human .ALPHA.1-Acid Glycoprotein

Abstract

We investigated the characteristics of binding of tamsulosin to a a 1 -acid glycoprotein (AGP) genetic variants. The binding of tamsulosin to each of the human AGP variants was determined by ultrafiltration, and the binding characteristics for each variant were compared using binding parameters and inhibition of the binding by disopyramide and warfarin. The affinities of tamsulosin binding to a F1/S variant mixture and total AGP variants were relatively high (dissociation constants 1.6 m mM). On the other hand, the dissociation constant for variant A was 14.9؎2.53 m mM. The binding of tamsulosin was competitively inhibited by warfarin but not by disopyramide. Tamsulosin appears to be a suitable compound for studying the characteristics of drug binding to human AGP F1/S variants under clinical conditions.

Lipophilicity Influences Drug Binding to α1-Acid Glycoprotein F1/S Variants But Not to the A Variant

“…(Tokyo, Japan) and 14 C-labeled warfarin was obtained from Amersham Biosciences Limited (Amersham, NJ, USA). Enantiomers of these drugs were separated by the enantioselective high-performance liquid chromatography (HPLC) method and their stereochemical purities were ascertained by stereoselective HPLC resolution, as reported previously [14]. Tamoxifen citrate and progesterone were obtained from Nakari Tesque (Kyoto, Japan).…”

“…The radio-labeled compounds were purified by HPLC as reported previously [13, 14], then dissolved in phosphate buffer and the solution was used on the same day. The binding of marker compounds to human AGP was determined by an ultrafiltration technique described previously [13, 14].…”

“…The binding of marker compounds to human AGP was determined by an ultrafiltration technique described previously [13, 14]. The binding of [ 3 H]tamsulosin was determined as follows: a 450-μL aliquot of commercial AGP was added to 50 µL of tamsulosin (40, 60, 80, 100, 150, 200, 300, or 500 μM) and 10 μL of [ 3 H]tamsulosin and 10 μL of the 14 drugs tested (9.62, 19.2, and 48.1 μM), and then the mixture was incubated for 15 min at 37 °C.…”

Development and Validation of Stability-Indicating HPTLC Determination of Tamsulosin in Bulk and Pharmaceutical Dosage Form

“…It is a white to yellowish-white powder, slightly soluble in water, soluble in methanol, and chloroform-administered orally. Literature survey reveals the chiral separation by electrophoresis [3,4], UV [5], and HPLC methods [6][7][8], coupled with ESI-MS-MS are reported for the estimation of tamsulosin hydrochloride with its impurities in bulk and pharmaceutical formulations [9] as well as in biological fluids [10][11][12][13][14][15][16][17]. The present work deals with HPTLC stability for tamsulosin hydrochloride in bulk and pharmaceutical formulation which is economical and intended for better reproducibility of degraded products, and this work is genuine as it is not used by any other author.…”