Intravenous administration of @entity4770 in XXXX : elimination kinetics and blood pressure response.

@entity1 @entity1423 @entity95 @entity4770 @entity857 @entity551
Prostacyclin (PGI2) has been used extensively in @entity1 clinical trials and animal studies, but because of its instability, knowledge of its pharmacokinetics has progressed slowly. We assayed plasma PGI2 concentrations with a quantitative chromatographic method following bolus intravenous injection and during continuous infusion in @entity95 . Blood pressure response was correlated with plasma PGI2 concentrations and compared with the concentrations necessary to inhibit @entity1423 in vitro. A two-compartment model was used to analyze the elimination kinetics for PGI2 after a single injection. The half-life of the terminal elimination phase was 2.7 minutes. The calculated systemic clearance and whole body volume of distribution were 93 ml/kg/min and 357 ml/kg, respectively. During continuous infusion, steady-state plasma concentrations were reached within 15 minutes and increased linearly with increasing infusion rate from 4.2 to 604 ng/kg/min, which resulted in PGI2 concentrations of 0.06 +/- 0.01 to 7.6 +/- 2.1 ng/ml, respectively. At steady-state plasma concentrations of PGI2 greater than 0.1 ng/ml, the mean arterial blood pressure decreased in a concentration-dependent manner, reaching a decrease of 45 mm Hg when the plasma concentration was 7.6 ng/ml. @entity4770 caused a concentration-dependent inhibition of @entity857 -induced @entity1423 in vitro with 10% inhibition at 0.4 ng/ml. These results indicate that in the @entity95 the level of PGI2 at which the onset of @entity551 occurs coincides with the inhibition of @entity1423 .
