Evidence for Non-Linear Pharmacokinetics of Oxytocin in Anesthetizetized Rat

Authors

  • Eric Troncy Université de Montréal
  • Valérie Morin
  • Jérôme R.E. del Castillo
  • Simon Authier
  • Norma Ybarra
  • Colombe Otis
  • Dominique Gauvin
  • Jolanta Gutkowska

DOI:

https://doi.org/10.18433/J3PK5X

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 (t½(λz) 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 t½(λz) 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.

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Author Biography

Eric Troncy, Université de Montréal

GREPAQ - Department of veterinary biomedicine Associate Professor in Physio-pharmacology

Published

2008-10-06

How to Cite

Troncy, E., Morin, V., del Castillo, J. R., Authier, S., Ybarra, N., Otis, C., … Gutkowska, J. (2008). Evidence for Non-Linear Pharmacokinetics of Oxytocin in Anesthetizetized Rat. Journal of Pharmacy & Pharmaceutical Sciences, 11(4), 12–24. https://doi.org/10.18433/J3PK5X

Issue

Section

Pharmaceutical Sciences; Original Research Articles