Effect of α1-acid glycoprotein on the pharmacokinetics of tamsulosin in rats treated with turpentine oil

✍ Scribed by Hiroshi Matsushima; Takashi Watanabe; Saburo Higuchi

• Publisher: John Wiley and Sons
• Year: 2000
• Tongue: English
• Weight: 249 KB
• Volume: 89
• Category: Article
• ISSN: 0022-3549
• DOI: 10.1002/(sici)1520-6017(200004)89:4<490::aid-jps6>3.0.co;2-o

✦ Synopsis

The pharmacokinetics of tamsulosin (TAM) was investigated using male Sprague-Dawley rats in which plasma ␣ 1 -acid glycoprotein (␣ 1 -AGP) levels were elevated by the subcutaneous injection of 0.2 mL/kg of turpentine oil. ␣ 1 -AGP levels increased about eight times after turpentine oil treatment, causing a threefold decrease in plasma unbound fraction (f u ) of TAM. When 0.3 mg/kg of TAM was dosed intravenously, total and nonrenal clearances (CL tot and CL nr ) in turpentine-treated rats were 47% and 44% lower than those in nontreated controls, respectively. The area under the concentration-time curve of plasma unbound TAM (AUC inf,u ) was lower than that in the control. When 1 mg/kg of TAM was dosed orally, oral clearance (CL oral ) in ␣1-AGPinduced rats was 65% lower than in the control. The AUC inf,u and unbound oral clearance (CL oral,u ) were nearly equal in both groups. Moreover, a positive correlation was observed between fu and CL oral of TAM (r 2 ‫ס‬ 0.603, P < 0.01), whereas no correlation was observed between f u and CL oral,u . The absolute bioavailability (BA) increased from 19.2% to 46.9% by induction of ␣ 1 -AGP. These results suggest that decreased f u caused by the elevation of plasma ␣ 1 -AGP level affects the pharmacokinetics of TAM, but does not affect the CL oral,u, which represents the hepatic metabolism of TAM.