Premium
Pharmacokinetics and bioavailability after intramuscular injection of the 5‐ HT 1A serotonin agonist R‐8‐hydroxy‐2‐(di‐n‐propylamino) tetralin (8‐ OH ‐ DPAT ) in domestic goats ( Capra aegagrus hircus )
Author(s) -
Pfitzer Silke,
Woodward Andrew P.,
Laubscher Liesel,
Warren Kristin,
VaughanHiggins Rebecca,
Raath Jacobus P.,
Laurence Michael
Publication year - 2019
Publication title -
journal of veterinary pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.527
H-Index - 60
eISSN - 1365-2885
pISSN - 0140-7783
DOI - 10.1111/jvp.12741
Subject(s) - bioavailability , pharmacokinetics , chemistry , agonist , pharmacology , toxicity , serotonin , receptor , medicine , biochemistry , organic chemistry
To determine the bioavailability and pharmacokinetic properties of the serotonin 5‐ HT 1A 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.