Disposition kinetics of taxanes after intraperitoneal administration in rats and influence of surfactant vehicles

Authors: Yokogawa K.1; Jin M.1; Furui N.1; Yamazaki M.1; Yoshihara H.1; Nomura M.1; Furukawa H.2; Ishizaki J.1; Fushida S.3; Miwa K.3; Miyamoto K-i.1

Source: Journal of Pharmacy and Pharmacology, Volume 56, Number 5, 1 May 2004 , pp. 629-634(6)

Publisher: Pharmaceutical Press

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Abstract:

Rats were intraperitoneally administered 40 mg kg-1 of paclitaxel or docetaxel dissolved in various drug solutions. The drug solutions were prepared using 20 mL of saline, adding 4.2% Cremophor EL (crEL) for paclitaxel (TXL), and 1.5% Polysorbate-80 (PS-80) (TXT), 7.5% PS-80 (TXT+PS-80) or 4.2% crEL (TXT+crEL) for docetaxel. The apparent first-order absorption rate constant from the peritoneal cavity (ka) of TXL was about one-twentieth of that of TXT. The ratio of the area under the concentration-time curve of drug in plasma over that in ascites for TXL was about one-third of that of TXT. The values of the above ratio and the ka of TXT+PS-80 and TXT+crEL were similar to those of TXL. After intraperitoneal administration, the values of the blood-to-plasma concentration ratio in the four groups were similar and independent of time. In the in-vitro study, PS-80 and crEL caused similar, concentration-dependent decreases of drug permeation into red blood cells after a 15-min incubation of rat blood with 10 mug mL-1 of TXL. We demonstrated that the disposition kinetics of taxanes after intraperitoneal administration to rats was strongly influenced, in a concentration-dependent manner, by the surfactant vehicle used, crEL or PS-80.

Document Type: Research article

DOI: 10.1211/0022357023303

Affiliations: 1: Department of Hospital Pharmacy, School of Medicine, Kanazawa University, 13-1 Takara-machi, Kanazawa 920-8641, Japan 2: Clinical Trial Control Center, School of Medicine, Kanazawa University, 13-1 Takara-machi, Kanazawa 920-8641, Japan 3: Department of Surgery II, School of Medicine, Kanazawa University, 13-1 Takara-machi, Kanazawa 920-8641, Japan

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