Pharmacokinetic evaluation of pancreatic arterial infusion chemotherapy with lipid emulsion as a drug carrier in an animal model

Anticancer Drugs. 2012 Aug;23(7):713-7. doi: 10.1097/CAD.0b013e3283512a68.

Abstract

The purpose of this study was to investigate the potential pharmacokinetic advantage of pancreatic arterial infusion chemotherapy with lipid emulsion as a drug carrier for pancreatic cancer in a dog model. The 20% Intralipid, as a solvent, was used in the experimental animals with 2 ml/kg (group A) and 1 ml/kg (group B). Normal sodium as a solvent was used as a control with 2 ml/kg (group C) and 1 ml/kg (group D), respectively. Cisplatin (4 mg/kg) was infused into the proximal segment of the splenic artery. The concentrations of cisplatin were measured in plasma of the portal vein and in the liver and pancreas of groups A and C. The area under the concentration-time curve (AUC), the maximum plasma concentration (C(max)), and the elimination half-life (t(1/2)) in plasma were calculated and compared statistically. Compared with group C, the AUC and C(max) of group A were significantly lower (P<0.01 and P<0.01, respectively), the t 1/2 was longer (P<0.05), and the tissue cisplatin concentration of the pancreas was higher (P<0.05). Compared with group D, the AUC and C(max) of group B were significantly lower (P<0.01 and P<0.01, respectively) and the t(1/2) was longer (P<0.01). Pancreatic arterial infusion chemotherapy with lipid emulsion as a drug carrier can increase the local concentration and prolong the retention time of a drug.

MeSH terms

  • Animals
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / pharmacokinetics*
  • Cisplatin / administration & dosage
  • Cisplatin / pharmacokinetics*
  • Dogs
  • Drug Carriers / administration & dosage
  • Drug Carriers / pharmacokinetics
  • Emulsions / administration & dosage
  • Emulsions / pharmacokinetics
  • Fat Emulsions, Intravenous / administration & dosage
  • Fat Emulsions, Intravenous / pharmacokinetics*
  • Infusions, Intra-Arterial / methods*
  • Models, Animal
  • Pancreas / blood supply
  • Pancreatic Neoplasms / drug therapy*
  • Phospholipids / administration & dosage
  • Phospholipids / pharmacokinetics*
  • Soybean Oil / administration & dosage
  • Soybean Oil / pharmacokinetics*
  • Splenic Artery

Substances

  • Antineoplastic Agents
  • Drug Carriers
  • Emulsions
  • Fat Emulsions, Intravenous
  • Phospholipids
  • soybean oil, phospholipid emulsion
  • Soybean Oil
  • Cisplatin