Disposition kinetics of taxanes after intraperitoneal administration in rats and influence of surfactant vehicles.
Rats were intraperitoneally administered 40 mg x 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 (k(a)) 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 k(a) 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 microg x 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.
Yokogawa
Koichi
K
Department of Hospital Pharmacy, School of Medicine, Kanazawa University, 13-1 Takara-machi, Kanazawa 920-8641, Japan.
Jin
Mingji
M
Furui
Naho
N
Yamazaki
Masaru
M
Yoshihara
Hiromi
H
Nomura
Masaaki
M
Furukawa
Hiroyuki
H
Ishizaki
Junko
J
Fushida
Sachio
S
Miwa
Kouichi
K
Miyamoto
Ken-ichi
K
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001201:Ascites / Q000378:metabolism; D000077143:Docetaxel; D004912:Erythrocytes / Q000378:metabolism; D005079:Excipients / Q000737:chemistry / Q000494:pharmacology; D005260:Female; D005990:Glycerol / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D066298:In Vitro Techniques; D007274:Injections, Intraperitoneal; D017239:Paclitaxel / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D010539:Permeability; D014677:Pharmaceutical Vehicles / Q000737:chemistry / Q000494:pharmacology*; D011136:Polysorbates / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D013501:Surface-Active Agents / Q000737:chemistry / Q000494:pharmacology*; D043823:Taxoids / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D013997:Time Factors; D014018:Tissue Distribution
D000972:Antineoplastic Agents, Phytogenic; D005079:Excipients; D014677:Pharmaceutical Vehicles; D011136:Polysorbates; D013501:Surface-Active Agents; D043823:Taxoids; D000077143:Docetaxel; C000515:cremophor EL; D017239:Paclitaxel; D005990:Glycerol