Changes in pharmacokinetics of cisplatin after hepatic resection in rats.
Adjuvant chemotherapy concomitant with hepatic resection has been considered as treatment of patients with hepatocarcinoma. To examine the influence of a partial hepatectomy on the platinum pharmacokinetics, rats were given a single dose of cisplatin (2 mg/kg) prior to 2/3 hepatic resection or sham operation. The partially hepatectomized rats showed a 44% increase in the AUC between 2-48 hr compared with the sham-operated controls. The terminal plasma half-life from 12-48 hr was 21.1 hr for the partially hepatectomized rats and 14.7 hr for the sham-operated animals. Total platinum concentration in liver tissue was 1.3 times that of plasma 20 min after injection. Although cisplatin is considered to be eliminated mainly via renal excretion, our finding may suggest a role for the liver in the elimination of platinum.
Department of Clinical Pharmacology, University of Oslo, Rikshospitalet.
K S
KS
Hall
B
B
Lien
L
L
Endresen
A
A
Bergan
H E
HE
Rugstad
D000818:Animals; D002945:Cisplatin / Q000097:blood / Q000493:pharmacokinetics*; D006400:Hematocrit; D006454:Hemoglobins / Q000378:metabolism; D006498:Hepatectomy; D008099:Liver / Q000378:metabolism / Q000601:surgery*; D008297:Male; D010984:Platinum / Q000097:blood / Q000378:metabolism; D011300:Preoperative Care; D051381:Rats; D011915:Rats, Inbred BUF
D006454:Hemoglobins; D010984:Platinum; D002945:Cisplatin