Pharmacokinetics of cisplatin regional hepatic infusions

Publisher Website
Google Scholar
Abstract
Cisplatin (DDP), a potent antineoplastic agent, is usually administered via a peripheral vein. Recently, there has been considerable interest in intraarterial regional infusions of DDP. The pharmacokinetics of DDP when administered by this technique have not been explored in detail. DDP pharmacokinetics was studied in dogs given DDP by infusion and bolus injection in the hepatic artery (H.A.), portal vein (portal V) and peripheral vein (P.V.). Blood and biliary Pt concentrations [Pt] were assayed by flameless atomic absorption spectrophotometry. During an infusion into the H.A., peak Pt in this vessel were markedly higher (mean value 19 .mu.g/ml) than those found simultaneously in the portal V or superior vena cava. Following a bolus injection of DDP into the H.A., higher H.A. (Pt) were also seen, but Pt rapidly (within 5-10 min) equilibrated in all sites sampled. During the H.A. infusion, most Pt was in its free (active) form. Bile and hepatic tissue were also sampled. Hepatic artery infusions of DDP give high drug concentrations in the perfusing blood; systemic Pt are much lower. During the infusion, the majority of DDP is in its active (unbound) state.