Effect of the ET(B) receptor agonist, IRL-1620, on paclitaxel plasma pharmacokinetics of breast tumor rats.

Abstract

Endothelin (ET)-B receptors are expressed in human breast carcinoma. We previously demonstrated that intravenous administration of the ET(B) receptor agonist, IRL-1620, to tumor-bearing rats, increased blood perfusion and enhanced delivery of paclitaxel to breast tumor tissue. The present study was conducted to determine whether IRL-1620 alters the pharmacokinetics of paclitaxel. Breast tumor-bearing rats were given 0.3 ml/kg saline or 3 nmol/kg IRL-1620 by intravenous (iv) administration. Fifteen minutes after saline or IRL-1620, 40 microCi/rat 3H-Paclitaxel was administered iv and serial plasma samples were collected until 24 hrs. 3H-Paclitaxel radioactivity in the plasma samples was measured by liquid scintillation counting. Data were fit to a three-compartment model and pharmacokinetic parameters were generated using WinNonlin software. IRL-1620 did not produce any change in the plasma paclitaxel pharmacokinetics of tumor-bearing rats. The AUC(0-infinity) (9.43 +/- 3.18 microg-hr/ml), clearance (0.69 +/- 0.17 l/hr/kg), volume of distribution (10.31 +/- 4.54 l/kg), and half-life (1.0 +/- 0.32 hrs) of paclitaxel were similar between rats treated with saline or IRL-1620. In conclusion, the ET(B) receptor agonist, IRL-1620, does not alter paclitaxel plasma pharmacokinetics and, therefore, could be used to augment the delivery of paclitaxel to the tumor tissue.

• Authors: Aarati Rai, N V Rajeshkumar, Anil Gulati
• Journal: Experimental biology and medicine (Maywood, N.J.) (Exp Biol Med (Maywood)) Vol. 231 Issue 6 Pg. 1120-2 (Jun 2006) ISSN: 1535-3702 [Print] England
• PMID: 16741060 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents, Phytogenic
• Endothelins
• Peptide Fragments
• Receptor, Endothelin B
• sovateltide
• Paclitaxel

Topics

• Animals
• Antineoplastic Agents, Phytogenic (blood, pharmacokinetics)
• Endothelins (pharmacology)
• Female
• Mammary Neoplasms, Animal (drug therapy)
• Paclitaxel (blood, pharmacokinetics)
• Peptide Fragments (pharmacology)
• Rats
• Rats, Sprague-Dawley
• Receptor, Endothelin B (agonists)