Enhanced oral bioavailability of paclitaxel by recombinant interleukin-2 in mice with murine Lewis lung carcinoma.
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.
Abbara
Chadi
C
Laboratoire de Pharmacologie, Service de Pharmacie, Hôpital Paul Brousse, Villejuif, France.
Rouchon
Christophe
C
Hosten
Benoît
B
Farinotti
Robert
R
Bonhomme-Faivre
Laurence
L
D000284:Administration, Oral; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000097:blood*; D001682:Biological Availability; D018827:Carcinoma, Lewis Lung / Q000097:blood*; D004357:Drug Synergism; D005260:Female; D007376:Interleukin-2 / Q000494:pharmacology*; D008175:Lung Neoplasms / Q000097:blood*; D051379:Mice; D008810:Mice, Inbred C57BL; D017239:Paclitaxel / Q000008:administration & dosage / Q000097:blood*; D011994:Recombinant Proteins / Q000494:pharmacology
D000972:Antineoplastic Agents, Phytogenic; D007376:Interleukin-2; D011994:Recombinant Proteins; D017239:Paclitaxel