Toxicity and pharmacokinetics of isolated lung perfusion with cisplatin in rat.
OBJECTIVE
This study was designed to evaluate the toxicity and the pharmacokinetics of cisplatin administered via isolated lung perfusion in Fischer 344 rat.


METHODS
Toxicity study; Cisplatin dosages of 3.3, 5.0, 6.7, and 10.0 mg/kg were injected intravenously in four groups, respectively. Cisplatin dosages of 3.3, 5.0, and 6.7 mg/kg were perfused via isolated lung perfusion in a further three groups, respectively. The maximum tolerated dosage of cisplatin was determined by assessing the survival rate on day 21. Pharmacokinetics study; Animals received 6.7 mg/kg of cisplatin intravenously or 3.3 mg/kg of cisplatin via isolated lung perfusion. The cisplatin levels of the lung were measured by flameless atomic spectrometry.


RESULTS
Toxicity study; The maximum tolerated dosage of cisplatin via intravenous injection was 6.7 mg/kg, and via isolated lung perfusion was 3.3 mg/kg. Pharmacokinetics study; The cisplatin level in the perfused lung was significantly higher than that in the lung of the animal treated intravenously (16.6 +/- 6.2 micrograms/g of tissue and 7.5 +/- 3.2 micrograms/g of tissue, respectively) (p = 0.0096).


CONCLUSIONS
Isolated lung perfusion with 3.3 mg/kg of cisplatin was pharmacokinetically superior to the maximum tolerated intravenous injection of cisplatin.
Kaneda
Y
Y
Department of Surgery I, Yamaguchi University School of Medicine, 1-1-1 Minami-Kogushi, Ube, Yamaguchi 755-8505, Japan.
Liu
D
D
Brooks
A
A
Abolhoda
A
A
Labow
D
D
Burt
M E
ME
Ginsberg
R J
RJ
D000818:Animals; D002945:Cisplatin / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000633:toxicity*; D004361:Drug Tolerance; D066298:In Vitro Techniques; D007275:Injections, Intravenous; D008168:Lung / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D010477:Perfusion; D051381:Rats; D011916:Rats, Inbred F344
D002945:Cisplatin