Enhanced oral bioavailability of paclitaxel by recombinant interleukin-2 in mice with murine Lewis lung carcinoma

Drug Metabol Drug Interact. 2004;20(4):219-31. doi: 10.1515/dmdi.2004.20.4.219.

Abstract

The effect of recombinant interleukin-2 (rIL-2) pretreatment on the pharmacokinetics of paclitaxel was investigated in the murine Lewis lung carcinoma model in C57B1/6 mice. Paclitaxel 15 mg/kg was administrated orally to mice, either alone or after 3 days pretreatment with twice daily dose of 16.5 microg rIL-2. Plasma concentrations of paclitaxel were estimated by reversed phase HPLC. Pharmacokinetic parameters were determined using MicroPharm software. Using Bailer's method, a significant difference was observed in the AUCs of paclitaxel administrated alone and with rIL-2 pretreatment (928.2 +/- 136.8 vs 2549.6 +/- 131.3 ng.h.ml(-1), p <0.0001). Pretreatment with rIL-2 resulted in a 3-fold increase in the oral bioavailability of paclitaxel without altering its elimination half-life (0.798 vs 0.747 h). This could be due to the inhibition of P-glycoprotein (P-gp) mediated transport, thus enhancing paclitaxel intestinal absorption. The combination of these two drugs could be of interest in clinical practice due to their activity in pulmonary cancer.

MeSH terms

  • Administration, Oral
  • Animals
  • Antineoplastic Agents, Phytogenic / administration & dosage
  • Antineoplastic Agents, Phytogenic / blood*
  • Biological Availability
  • Carcinoma, Lewis Lung / blood*
  • Drug Synergism
  • Female
  • Interleukin-2 / pharmacology*
  • Lung Neoplasms / blood*
  • Mice
  • Mice, Inbred C57BL
  • Paclitaxel / administration & dosage
  • Paclitaxel / blood*
  • Recombinant Proteins / pharmacology

Substances

  • Antineoplastic Agents, Phytogenic
  • Interleukin-2
  • Recombinant Proteins
  • Paclitaxel