Effect of repeated intraperitoneal chemotherapy with epirubicin on the hepatic transport of bile acids and their enterohepatic circulation.
The effect of repeated intraperitoneal perfusion with epirubicin on the clearance of 14C-taurocholate by the liver and the enterohepatic circulation of the synthetic bile acid 75-SeHCAT were investigated using a rat model. After six treatments there was no significant difference in the transport rate constants (plasma to liver, liver to bile and liver to plasma) between and within the saline and epirubicin groups. Similarly, there were no differences detected between the groups for the parameters derived from these transport rate constants. Thus the initial plasma clearance after six perfusions was 39 +/- 9, and 36 +/- 11 ml/min/kg in the epirubicin and saline groups respectively. The excretory efficiency of the liver at this stage was identical: 67 +/- 10% in the epirubicin treated animals and 67 +/- 6% in the saline controls. A deterioration in the SeHCAT retention was observed after repeated intraperitoneal perfusion in both groups. This was significant only in the cytotoxic group, between the first and sixth epirubicin perfusion: 59 +/- 9% vs 48 +/- 9% at 24 h (P = 0.03), 31 +/- 8% vs 22 +/- 5% at 48 h (P = 0.019) and was not cumulative beyond this stage. These findings indicate that repeated intraperitoneal perfusion chemotherapy with epirubicin does not impair bile acid clearance by the hepatocyte. The decrease in the retention of SeHCAT is unlikely to be the result of epirubicin-induced ileal mucosal damage since the reduction was not cumulative beyond 48 h of administration of the compound.
Hastie
K J
KJ
Department of Surgery, Ninewells Hospital and Medical School, University of Dundee, Scotland, UK.
Baker
P R
PR
Reid
A
A
Cuschieri
A
A
D000818:Animals; D001647:Bile Acids and Salts / Q000493:pharmacokinetics*; D001692:Biological Transport / Q000187:drug effects; D015251:Epirubicin / Q000008:administration & dosage / Q000009:adverse effects*; D007263:Infusions, Parenteral; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008657:Metabolic Clearance Rate / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D012644:Selenium Radioisotopes; D013656:Taurocholic Acid / Q000031:analogs & derivatives* / Q000493:pharmacokinetics
D001647:Bile Acids and Salts; D012644:Selenium Radioisotopes; D015251:Epirubicin; D013656:Taurocholic Acid; C033638:23-seleno-25-homotaurocholic acid