Effect of the ET(B) receptor agonist, IRL-1620, on paclitaxel plasma pharmacokinetics of breast tumor rats.
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.
Rai
Aarati
A
Department of Biopharmaceutical Sciences (M/C 865), The University of Illinois at Chicago, 833 South Wood Street, Chicago, IL 60612, USA.
Rajeshkumar
N V
NV
Gulati
Anil
A
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000097:blood / Q000493:pharmacokinetics*; D016232:Endothelins / Q000494:pharmacology*; D005260:Female; D015674:Mammary Neoplasms, Animal / Q000188:drug therapy*; D017239:Paclitaxel / Q000097:blood / Q000493:pharmacokinetics*; D010446:Peptide Fragments / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D044023:Receptor, Endothelin B / Q000819:agonists*
D000972:Antineoplastic Agents, Phytogenic; D016232:Endothelins; D010446:Peptide Fragments; D044023:Receptor, Endothelin B; C074308:sovateltide; D017239:Paclitaxel