The tissue distribution in rats of [195mPt]carboplatin following intravenous, intraperitoneal and oral administration.
[195mPt]carboplatin has been administered intravenously, intraperitoneally and orally to Wistar rats and the tissue distribution, metabolism, and pharmacokinetics of the drug investigated. The urinary and faecal excretion and toxicity following oral [195mPt]carboplatin administration has also been studied. Virtually identical results have been observed following i.v. and i.p. administration, indicating a rapid absorption of the unaltered compound from the abdominal cavity into the systemic circulation. Thus i.p. administered drug should produce a similar therapeutic response as i.v. administration, but may produce an additional local effect within the peritoneal cavity. Orally administered compound shows a pattern of distribution which is similar to that following parenteral injection for all tissues (except for the increased relative concentration in the stomach tissue), the concentration being lower by a factor of 4-5. However, the overall fraction of the dose retained within the body at 24 h is similar to that following i.v. administration. The toxicity is considerably lower for the orally administered drug compared with i.v. injection. These results clearly show that oral doses could be adjusted to produce a comparable therapeutic effect as i.v. or i.p. doses, and should also result in a higher efficacy against gastric carcinomas than achievable with parenteral administration.
Department of Chemistry, UMIST, Manchester, U.K.
N
N
Tinker
B
B
De Spiegeleer
H
H
Sharma
H
H
Jackson
C
C
McAuliffe
J P
JP
Reman
D000284:Administration, Oral; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000633:toxicity; D016190:Carboplatin; D007274:Injections, Intraperitoneal; D007275:Injections, Intravenous; D008297:Male; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000633:toxicity; D010984:Platinum; D011868:Radioisotopes; D051381:Rats; D011919:Rats, Inbred Strains; D014018:Tissue Distribution
D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D011868:Radioisotopes; D010984:Platinum; D016190:Carboplatin