Isolated pelvic perfusion: plasma pharmacokinetics depend primarily on drug dosage and not the type of drug.
OBJECTIVE
Comparison of the pharmacokinetics of four drugs with the isolated pelvic perfusion protocol showed linear relationships between drug dosage and two isolated pelvic plasma parameters, mean AUC (pelvic exposure, microM min) and the mean maximum pelvic drug level (microM). It appears that the pharmacokinetics are sufficiently defined as to predict plasma distribution curves for an additional drug with this protocol. Recent FDA approval of oxaliplatin allowed an evaluation of this premise.


METHODS
Linearity of drug dosage with maximum drug levels and exposure (AUC) in the isolated pelvic plasma yields initial estimates of these parameters for additional drugs. Use of an empirical, four-compartment pharmacokinetic model (Wanebo and Belliveau in Cancer Chemother. Pharmacol. 43:427, 1999) allowed the generation of predictive plasma distribution curves. These curves were established by optimizing the initial estimates of maximum drug levels and exposure along with estimates of two additional parameters (half-life of pelvic clearance and pelvic to systemic exposure ratio) from experimental data of the four drugs pharmacokinetically characterized.


RESULTS
Calculated plasma distribution curves for oxaliplatin matched the experimental curves from the first three patients receiving oxaliplatin therapy, given the experimental ranges of pharmacokinetic parameters seen with the initial four drugs.


CONCLUSIONS
These results give an overall picture for the plasma pharmacokinetics during the isolation period for the isolated pelvic perfusion protocol. Enough experimental data have been accumulated for five drugs to establish a simple pharmacokinetic model (Wanebo and Belliveau in Cancer Chemother Pharmacol 43:427, 1999) and interdrug relationships (i.e., this report) which can be used to predict reasonable plasma distribution curves for additional drugs with this protocol.
Belliveau
James F
JF
Departments of Chemistry and Biochemistry, Providence College, 549 River Avenue, Providence, RI, 02918, USA. bells@providence.edu.
Arevalo
Elisabeth
E
Department of Biology, Providence College, 549 River Avenue, Providence, RI, 02918, USA.
Griffin
Hank
H
Departments of Chemistry and Biochemistry, Providence College, 549 River Avenue, Providence, RI, 02918, USA.
Wanebo
Harold J
HJ
Division of Surgical Oncology, Roger Williams Medical Center/Boston University School of Medicine, Providence, RI, 02908, USA.
D000465:Algorithms; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000097:blood* / Q000493:pharmacokinetics; D010478:Chemotherapy, Cancer, Regional Perfusion; D006801:Humans; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D000077150:Oxaliplatin; D010386:Pelvic Neoplasms / Q000097:blood / Q000188:drug therapy*
D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin