Evidence for Non-Linear Pharmacokinetics of Oxytocin in Anesthetizetized Rat
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, 10...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2008-10-01
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| Series: | Journal of Pharmacy & Pharmaceutical Sciences |
| Online Access: | https://journals.library.ualberta.ca/jpps/index.php/JPPS/article/view/4150 |
| _version_ | 1797728812825313280 |
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| author | Eric Troncy Valérie Morin Jérôme R.E. del Castillo Simon Authier Norma Ybarra Colombe Otis Dominique Gauvin Jolanta Gutkowska |
| author_facet | Eric Troncy Valérie Morin Jérôme R.E. del Castillo Simon Authier Norma Ybarra Colombe Otis Dominique Gauvin Jolanta Gutkowska |
| author_sort | Eric Troncy |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-12T11:19:31Z |
| format | Article |
| id | doaj.art-2832c824b7d64d5abec3d558c51ca373 |
| institution | Directory Open Access Journal |
| issn | 1482-1826 |
| language | English |
| last_indexed | 2024-03-12T11:19:31Z |
| publishDate | 2008-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Journal of Pharmacy & Pharmaceutical Sciences |
| spelling | doaj.art-2832c824b7d64d5abec3d558c51ca3732023-09-02T00:49:03ZengFrontiers Media S.A.Journal of Pharmacy & Pharmaceutical Sciences1482-18262008-10-0111410.18433/J3PK5XEvidence for Non-Linear Pharmacokinetics of Oxytocin in Anesthetizetized RatEric Troncy0Valérie MorinJérôme R.E. del CastilloSimon AuthierNorma YbarraColombe OtisDominique GauvinJolanta GutkowskaUniversité de MontréalPurpose: 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.https://journals.library.ualberta.ca/jpps/index.php/JPPS/article/view/4150 |
| spellingShingle | Eric Troncy Valérie Morin Jérôme R.E. del Castillo Simon Authier Norma Ybarra Colombe Otis Dominique Gauvin Jolanta Gutkowska Evidence for Non-Linear Pharmacokinetics of Oxytocin in Anesthetizetized Rat Journal of Pharmacy & Pharmaceutical Sciences |
| title | Evidence for Non-Linear Pharmacokinetics of Oxytocin in Anesthetizetized Rat |
| title_full | Evidence for Non-Linear Pharmacokinetics of Oxytocin in Anesthetizetized Rat |
| title_fullStr | Evidence for Non-Linear Pharmacokinetics of Oxytocin in Anesthetizetized Rat |
| title_full_unstemmed | Evidence for Non-Linear Pharmacokinetics of Oxytocin in Anesthetizetized Rat |
| title_short | Evidence for Non-Linear Pharmacokinetics of Oxytocin in Anesthetizetized Rat |
| title_sort | evidence for non linear pharmacokinetics of oxytocin in anesthetizetized rat |
| url | https://journals.library.ualberta.ca/jpps/index.php/JPPS/article/view/4150 |
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