Mitomycin C-loaded microcapsules in the treatment of colorectal liver metastases. Pharmacokinetics of regionally administered particulate chemotherapy.
Microencapsulated mitomycin C has been used for the treatment of intrahepatic tumors in Japan, but there have been no reports of its use in western countries. In this study, the pharmacokinetic profile of intrahepatic arterial mitomycin C microcapsules is reported. Regional mitomycin C was administered to six patients, both in the microencapsulated form and in solution. The clearance (140 +/- 31 1/hour, mean +/- SD) and half-life of drug in plasma (0.39 +/- 0.03 hours), and volume distribution (246 +/- 23 1) were significantly higher, and peak drug concentrations (80 +/- 75 ng/ml) significantly lower with the microencapsulated preparation than with the free drug (clearance, 46 +/- 8 1/hour; half-life, 0.11 +/- 0.02 hours; volume distribution, 33 +/- 4; peak drug concentration, 812 +/- 423 ng/ml), on Student's t testing (P less than 0.05). The results show that very little systemic exposure is associated with the microencapsulated form of mitomycin C. Dose escalation should be feasible without increasing systemic toxicity.
Goldberg
J A
JA
University Department of Surgery, Royal Infirmary, Glasgow, UK.
Kerr
D J
DJ
Blackie
R
R
Whately
T L
TL
Pettit
L
L
Kato
T
T
McArdle
C S
CS
D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D015179:Colorectal Neoplasms; D004339:Drug Compounding; D006207:Half-Life; D006499:Hepatic Artery; D006801:Humans; D007261:Infusions, Intra-Arterial; D007958:Leukocyte Count / Q000187:drug effects; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000556:secondary*; D016685:Mitomycin; D008937:Mitomycins / Q000008:administration & dosage* / Q000493:pharmacokinetics; D010976:Platelet Count / Q000187:drug effects
D000970:Antineoplastic Agents; D008937:Mitomycins; D016685:Mitomycin