Pharmacokinetics and bioavailability after intramuscular injection of the 5-HT1A serotonin agonist R-8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) in domestic goats (Capra aegagrus hircus)

S. Pfitzer; A.P. Woodward; L. Laubscher; K. Warren; R. Vaughan-Higgins; J.P. Raath; M. Laurence

doi:10.1111/jvp.12741

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Pharmacokinetics and bioavailability after intramuscular injection of the 5-HT1A serotonin agonist R-8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) in domestic goats (Capra aegagrus hircus)

Journal article

Peer reviewed

Pharmacokinetics and bioavailability after intramuscular injection of the 5-HT1A serotonin agonist R-8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) in domestic goats (Capra aegagrus hircus)

S. Pfitzer, A.P. Woodward, L. Laubscher, K. Warren, R. Vaughan-Higgins, J.P. Raath and M. Laurence

Journal of Veterinary Pharmacology and Therapeutics, Vol.42(3), pp.251-257

2019

DOI: https://doi.org/10.1111/jvp.12741

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Abstract

To determine the bioavailability and pharmacokinetic properties of the serotonin 5-HT1A receptor agonist R-8-OH-DPAT in goats, and 0.1 mg kg−1 R-8-OH-DPAT hydrobromide was administered intramuscularly (i.m.) and intravenously (i.v.) to six goats in a two-phase cross-over design experiment. Venous blood samples were collected from the jugular vein 2, 5, 10, 15, 20, 30, 40 and 60 min following treatment and analysed by liquid chromatography tandem mass spectrometry. Bioavailability and pharmacokinetic parameters were determined by a one-compartment analysis. Mean bioavailability of R-8-OH-DPAT when injected i.m. was 66%. The mean volume of distribution in the central compartment was 1.47 L kg−1. The mean plasma body clearance was 0.056 L kg−1 min−1. All goats injected i.v. and two of six goats injected i.m. showed signs of serotonin toxicity. In conclusion, R-8-OH-DPAT is well absorbed following i.m. injection and the observed pharmacokinetics suggest that administration via dart is feasible. Administration of R-8-OH-DPAT hydrobromide, at a dosage of 0.1 mg kg−1, resulted in the observation of clinical signs of serotonin toxicity in the goats. It is suggested that dosages for the clinical use of the compound should be lower in order to achieve the desired clinical effect without causing serotonin toxicity.

Details

Title: Pharmacokinetics and bioavailability after intramuscular injection of the 5-HT1A serotonin agonist R-8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) in domestic goats (Capra aegagrus hircus)
Authors/Creators: S. Pfitzer (Author/Creator)
A.P. Woodward (Author/Creator)
L. Laubscher (Author/Creator)
K. Warren (Author/Creator)
R. Vaughan-Higgins (Author/Creator)
J.P. Raath (Author/Creator)
M. Laurence (Author/Creator)
Publication Details: Journal of Veterinary Pharmacology and Therapeutics, Vol.42(3), pp.251-257
Publisher: Blackwell Publishing Ltd
Identifiers: 991005545093307891
Copyright: © 2019 John Wiley & Sons Ltd
Murdoch Affiliation: School of Veterinary and Life Sciences
Language: English
Resource Type: Journal article

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Collaboration types: Domestic collaboration; International collaboration
Citation topics: 1 Clinical & Life Sciences; 1.218 Autonomic Regulation; 1.218.658 Respiratory Control
Web Of Science research areas: Pharmacology & Pharmacy; Veterinary Sciences
ESI research areas: Plant & Animal Science