Enhanced oral bioavailability of paclitaxel by recombinant interleukin-2 in mice with murine Lewis lung carcinoma |
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Authors: | Abbara Chadi Rouchon Christophe Hosten Benoît Farinotti Robert Bonhomme-Faivre Laurence |
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Affiliation: | Laboratoire de Pharmacologie, Service de Pharmacie, H?pital Paul Brousse, Villejuif, France. |
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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. |
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