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Pharmacokinetics and in vitro effects of imipramine hydrochloride on the vas deferens in cattle

Dissertation (MMedVet (Gyn))--University of Pretoria, 2005.

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Other Authors: Bertschinger, H.J. (Hendrik Jan)
Format: Thesis
Published: University of Pretoria 2013
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access_status_str Open Access
author2 Bertschinger, H.J. (Hendrik Jan)
author_browse Bertschinger, H.J. (Hendrik Jan)
author_facet Bertschinger, H.J. (Hendrik Jan)
collection Thesis
dc_rights_str_mv © 2005, University of Pretoria. All rights reserved. The copyright in this work vests in the University of Pretoria. No part of this work may be reproduced or transmitted in any form or by any means, without the prior written permission of the University of Pretoria.
description Dissertation (MMedVet (Gyn))--University of Pretoria, 2005.
format Thesis
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institution University of Pretoria (South Africa)
last_indexed 2026-06-10T12:37:51.914Z
license_str Other — see source repository
provenance_str_mv Harvested via OAI-PMH from UPSpace — University of Pretoria Institutional Repository
publishDate 2013
publishDateRange 2013
publishDateSort 2013
publisher University of Pretoria
publisherStr University of Pretoria
record_format dspace
source_str UPSpace — University of Pretoria Institutional Repository
spelling oai:repository.up.ac.za:2263/23159 Pharmacokinetics and in vitro effects of imipramine hydrochloride on the vas deferens in cattle Bertschinger, H.J. (Hendrik Jan) fertility@tah.co.za Cordel, Claudia Intravenous pharmacokinetics Domestic bull Imipramine hydrochloride UCTD Dissertation (MMedVet (Gyn))--University of Pretoria, 2005. This project was divided into two studies. The first investigated the pharmacokinetics of imipramine hydrochloride (IMI) in bulls. IMI was administered intravenously to three bulls (600-705.5 kg) at a dose of 2mg/kg body weight (BW). Intravenous plasma concentrations of IMI over time were determined by fluorescence polarization immunoassay (FPIA). IMI plasma concentration versus time profile was best described by a two compartmental open model with first-order rate constants. IMI distributed rapidly, (t½<font face="symbol">a</font>) at 7.2 ± 4.2 min, exhibited a very large apparent steady state volume of distribution (Vdss) of 4.2 ± 0.9 <font face="symbol">l</font>/kg BW, had a very short terminal elimination half-life (t½<font face="symbol">b</font>) of 140 ± 15 min and showed a rapid total body clearance (C<font face="symbol">l</font>) of 22.7 ± 7 m<font face="symbol">l</font>/min/kg. Both IMI and the pharmacologically active metabolite, desipramine was negligible in serum at 24 hours. All three bulls treated with IMI showed pronounced central nervous system signs immediately post injection. Signs of generalised weakness and ataxia were evident. All CNS signs dissipated 15-20 minutes post injection and should therefore not influence the treatment interval. An interval of at least 23 hours between repeat treatments of IMI, representing a period of at least 10 half-lives, is recommended. The dose of 2 mg/kg BW used in this study was similar to that routinely used in stallions without fatal side effects. One of the three bulls exhibited spontaneous emission and ejaculation with this dose. The second study investigated the effects of IMI on ampullar strips of bulls in organ baths. Vasa deferentia were collected from 16 freshly slaughtered post-puberal bulls of various breeds. Longitudinal ampullar strips were prepared and placed into 20 ml modified Krebs bicarbonate solution, aerated with a mixture of 02 (95 %) and CO2 (5 %) in water-jacketed organ baths. The effect on the smooth muscle tissue of noradrenaline (NA) alone, NA in combination with IMI and IMI alone was evaluated. NA alone consistently produced dose-dependant smooth muscle tissue contractions. IMI doses equivalent to <1 mg/kg BW (body weight equivalent; bwe) had NA potentiating effects. Doses of <0.1 mg/kg bwe were consistently potentiating while doses of >0.1 mg to <1 mg/kg bwe partially blocked NA stimulating effects. Amplitude of rhythmic contractions increased while contraction frequency decreased at this level. This study supports the adrenergic potentiating effects of IMI at doses of 0.05-0.2 mg/kg bwe with higher doses having paradoxical effects. Doses of IMI < 2 mg/kg bwe completely blocked NA effects. Tissue response to NA, after IMI blockade, started to recover 146-186 minutes after application of IMI at <2 mg/kg bwe. In the absence of NA, IMI had no effect on smooth muscle activity. The time to an IMI effect on NA initiated smooth muscle activity was 8 minutes. On the basis of the results of this in vitro study, we propose that IMI can be used to enhance semen collection by means of electro-stimulation in domestic bulls and immobilised wildlife species such as buffalo, provided that the correct dose is used. Production Animal Studies unrestricted 2013-09-06T14:40:32Z 2006-03-13 2013-09-06T14:40:32Z 2005-07-06 2007-03-13 2006-03-13 Dissertation Cordel, C 2005, Pharmacokinetics and in vitro effects of imipramine hydrochloride on the vas deferens in cattle, MMedVet dissertation, University of Pretoria, Pretoria, viewed yymmdd < http://hdl.handle.net/2263/23159 > http://hdl.handle.net/2263/23159 http://upetd.up.ac.za/thesis/available/etd-03132006-113241/ © 2005, University of Pretoria. All rights reserved. The copyright in this work vests in the University of Pretoria. No part of this work may be reproduced or transmitted in any form or by any means, without the prior written permission of the University of Pretoria. application/pdf University of Pretoria
spellingShingle Intravenous pharmacokinetics
Domestic bull
Imipramine hydrochloride
UCTD
Pharmacokinetics and in vitro effects of imipramine hydrochloride on the vas deferens in cattle
title Pharmacokinetics and in vitro effects of imipramine hydrochloride on the vas deferens in cattle
title_full Pharmacokinetics and in vitro effects of imipramine hydrochloride on the vas deferens in cattle
title_fullStr Pharmacokinetics and in vitro effects of imipramine hydrochloride on the vas deferens in cattle
title_full_unstemmed Pharmacokinetics and in vitro effects of imipramine hydrochloride on the vas deferens in cattle
title_short Pharmacokinetics and in vitro effects of imipramine hydrochloride on the vas deferens in cattle
title_sort pharmacokinetics and in vitro effects of imipramine hydrochloride on the vas deferens in cattle
topic Intravenous pharmacokinetics
Domestic bull
Imipramine hydrochloride
UCTD
url http://hdl.handle.net/2263/23159
http://upetd.up.ac.za/thesis/available/etd-03132006-113241/