Evidence for non-linear pharmacokinetics of oxytocin in anesthetizetized rat.

Abstract:

PURPOSE:Because oxytocin (OT) is potentially useful in cardiovascular therapy but has hormonal roles on the cardiovascular and renal systems, we characterized its pharmacokinetic (PK) properties as a function of dose. METHODS:A single intravenous bolus of OT was given at doses of 200, 300, 500, 1000, 3000, 5000 and 10000 ng/kg to anesthetized male rats (n >= 4 per dose). Blood samples (6) were taken over 72 min to 150 min, depending on dose. The individual time-courses of plasma OT concentrations were analyzed with a one- or an open two-compartment PK model. Kruskal-Wallis tests (alpha=0.05) were used to compare the PK parameters among groups. RESULTS:At doses up to 500 ng/kg, OT showed a higher median systemic clearance (CLT = 0.0624 L/(min*kg); 0.0622 +/- 0.0228 as mean +/- SD value), a higher median central compartment volume of distribution (VC = 0.7906 L/kg; 0.6961 +/- 0.1754), and a lower median elimination half life (t(1/2)(lambdaz) 7.94 min; 9.08 +/- 4.3) with respect to the higher doses (CLT = 0.0266 L/(min*kg); 0.0284 +/- 0.0098, VC = 0.2213 L/kg; 0.2227 +/- 0.1142, and t(1/2)(lambdaz) 21.09 min; 28.36 +/- 21.8), all differences being significant (p 0.0008). Minimal differences were found for the estimates of these PK parameters among the 4 higher OT doses. CONCLUSION:The PK properties and persistence of exogenous OT are not proportional to dose, therefore this must be accounted for in dosing regimen design for potential cardiovascular therapy.

journal_name

J Pharm Pharm Sci

authors

Morin V,Del Castillo JR,Authier S,Ybarra N,Otis C,Gauvin D,Gutkowska J,Troncy E

doi

10.18433/j3pk5x

subject

Has Abstract

pub_date

2008-01-01 00:00:00

pages

12-24

issue

4

issn

1482-1826

journal_volume

11

pub_type

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