Plasma protein binding of tamsulosin hydrochloride in renal disease: role of alpha1-acid glycoprotein and possibility of binding interactions.
OBJECTIVE
To investigate the factors that affect the plasma protein binding of tamsulosin in patients with lowered renal function compared with that in healthy subjects and to evaluate the possibility of binding interactions.


METHODS
Blood was donated from patients with renal dysfunction and from healthy subjects. The binding of 14C-tamsulosin to plasma proteins was determined by the ultrafiltration method. In addition, plasma protein binding interactions were investigated between tamsulosin and other drugs used concomitantly.


RESULTS
The mean percentage of unbound 14C-tamsulosin was 0.90% in the healthy subjects (control) and was 0.71% in the patients. The unbound fraction in the patients with alpha1-acid glycoprotein (alpha1-AGP) levels over 0.9 mg/ml was significantly lower than that in the healthy subjects. In contrast, the unbound fraction in the patients with alpha1-AGP levels less than 0.7 mg/ml, which is the mean normal level, was almost equal to the control levels. A significant correlation existed between the Cb/Cu of tamsulosin and plasma alpha1-AGP level (r2 = 0.580, P < 0.001), while no correlation existed between the Cb/Cu and plasma albumin level (r2 = 0.021, P = 0.381) in both groups. No apparent binding interactions were observed between tamsulosin and the other drugs examined.


CONCLUSIONS
Tamsulosin is highly bound to alpha1-AGP. The extent of plasma protein binding of tamsulosin correlated with the alpha1-AGP level but not with the albumin level. Furthermore, there appears to be no or little possibility of binding interactions between tamsulosin and other drugs in clinically concomitant use, despite its strong binding to alpha1-AGP.
Matsushima
H
H
Drug Metabolism Laboratories, Yamanouchi Pharmaceutical Co., Ltd., Tokyo, Japan. matsushi@yamanouchi.co.jp
Kamimura
H
H
Soeishi
Y
Y
Watanabe
T
T
Higuchi
S
S
Miyazaki
M
M
D000317:Adrenergic alpha-Antagonists / Q000493:pharmacokinetics*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D006801:Humans; D007674:Kidney Diseases / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009961:Orosomucoid / Q000378:metabolism*; D011485:Protein Binding; D013449:Sulfonamides / Q000493:pharmacokinetics*; D000077409:Tamsulosin
D000317:Adrenergic alpha-Antagonists; D009961:Orosomucoid; D013449:Sulfonamides; D000077409:Tamsulosin