Evidence for Non-Linear Pharmacokinetics of Oxytocin in Anesthetizetized Rat

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Title Evidence for Non-Linear Pharmacokinetics of Oxytocin in Anesthetizetized Rat
Creator Troncy, Eric
Morin, Valérie
del Castillo, Jérôme R.E.
Authier, Simon
Ybarra, Norma
Otis, Colombe
Gauvin, Dominique
Gutkowska, Jolanta
Description 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.
Publisher Canadian Society for Pharmaceutical Sciences
Contributor Canadian Institutes of Health Research and the Heart and Stroke Foundation of Canada, New Emerging Team (#108291) program
Date 2008-10-06
Type info:eu-repo/semantics/article

Format application/pdf
Identifier https://journals.library.ualberta.ca/jpps/index.php/JPPS/article/view/4150
Source Journal of Pharmacy & Pharmaceutical Sciences; Vol 11, No 4 (2008); 12-24
Journal of Pharmacy & Pharmaceutical Sciences; Vol 11, No 4 (2008); 12-24
Language eng
Relation https://journals.library.ualberta.ca/jpps/index.php/JPPS/article/view/4150/3459

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