Plasma and tissue disposition of paclitaxel (taxol) after intraperitoneal administration in mice.
The pharmacokinetics of single intraperitoneal doses of paclitaxel (18 and 36 mg/kg) in mice were investigated in the present study. The analysis of drug concentrations by HPLC indicated that the plasma Cmax (13.0 +/- 3.1 and 25.7 +/- 2.8 micrograms/ml, respectively) were reached at the 2nd hr. The values of CL were low (0.06 and 0.1 ml/min, respectively), and t1/2 beta values of 3.0 and 3.7 hr were found, after 18 and 36 mg/kg, respectively. The highest tissue concentrations were observed in the liver (50.2 +/- 3.1 and 92.0 +/- 9.5 micrograms/g respectively), followed by the pancreas (39.3 +/- 9.9 micrograms/g) and the ovary (53.4 +/- 5.6 micrograms/g) after 18 and 36 mg/kg, respectively. In the case of the colic tissue, paclitaxel Cmax were 14.4 +/- 0.8 and 32.8 +/- 3.5 micrograms/g at the 3rd hr, respectively, with sustained drug levels still detectable 24 hr after treatment. Paclitaxel Cmax values of 12.7 +/- 3.0 and 53.4 +/- 5.6 micrograms/g were detected in the ovary after 18 and 36 mg/kg, respectively. The overall results provide evidence that, after intraperitoneal administration, paclitaxel concentrates in peritoneal organs; however, the intraperitoneal route does not prevent systemic drug exposure, allowing high and sustained levels of paclitaxel also in several extraperitoneal tissues.
Innocenti
F
F
Institute of Medical Pharmacology, University of Pisa, Italy.
Danesi
R
R
Di Paolo
A
A
Agen
C
C
Nardini
D
D
Bocci
G
G
Del Tacca
M
M
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000097:blood / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D005260:Female; D007274:Injections, Intraperitoneal; D051379:Mice; D017239:Paclitaxel / Q000097:blood / Q000493:pharmacokinetics*; D014018:Tissue Distribution
D000972:Antineoplastic Agents, Phytogenic; D017239:Paclitaxel