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Prothipendyl: detection and elimination in the horse–a case report.

Abstract: The azaphenothiazine neuroleptic prothipendyl (Dominal) is suspected to be administered illegally at low doses to race-horses to improve their performance. Since for this species pharmacokinetic data of the drug are missing we studied its elimination from blood and urine in a standard-bred mare. At a low (subtherapeutic) dose (i.v., 0.24 mg/kg) the horse is described to be less excited while locomotor activity and attention remain unaffected. In contrast, sedation and ataxia are brought about at 1 mg/kg (therapeutic dose). Identification of prothipendyl given i.v. at subtherapeutic doses was achieved in blood only by means of gas chromatography-mass spectrometry (GC-MS), while the neuroleptic was found both in blood and urine upon 1 mg/kg. Quantification of the neuroleptic was carried out by virtue of triflupromazine as internal standard with the MS operating in the selected ion monitoring (SIM) mode. Under these conditions, the detection limit was 10 ng/ml body fluid. Disappearance of prothipendyl from blood was determined in the horse studied from terminal elimination process, yielding a t1/2 of 2.4 h. The results suggest that for detection of prothipendyl in the horse--in contrast to phenothiazine neuroleptics--screening of blood is preferred over urine as the drug was not recovered in urine after administration of subtherapeutic doses.
Publication Date: 1996-04-01 PubMed ID: 8925772
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  • Journal Article

Summary

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This study focused on the detection and elimination of the neuroleptic drug prothipendyl in racehorses where it is suspected of being illegally administered at low doses to enhance performance. It specifically examined its elimination from blood and urine in a standard-bred mare, how its effects varied between subtherapeutic and therapeutic doses, and how effectively it could be detected in blood and urine via gas chromatography-mass spectrometry (GC-MS).

Study Methodology

Experiments were carried out using a standard-bred mare, to whom prothipendyl was administered intravenously:

  • A low (subtherapeutic) dose of 0.24 mg/kg resulted in the horse appearing less excited, though its locomotor activity and attention appeared to remain unaffected.
  • A therapeutic dose of 1 mg/kg resulted in the noticeable effects of sedation and ataxia (lack of voluntary coordination of muscle movements) in the horse.

Detection of Prothipendyl in Blood and Urine

Gas chromatography-mass spectrometry (GC-MS) was used to identify prothipendyl in the horse’s bloodstream:

  • At the lower dose, the drug could only be detected in the blood using this method.
  • At the therapeutic dose, prothipendyl was detected in both blood and urine.

In order to quantify the amount of the drug, triflupromazine was used as an internal standard. The mass spectrometer was operated in the selected ion monitoring (SIM) mode. The detection limit under these conditions was found to be 10 ng/ml of body fluid.

Elimination of Prothipendyl from Blood

The rate at which prothipendyl was eliminated from the horse’s bloodstream was measured. The half-life (t1/2) of the drug was found to be 2.4 hours.

Conclusions

Based on these results, the researchers concluded that when testing for prothipendyl use in horses, blood screening appears to be more effective than urine testing, as the drug was not found in urine following the administration of subtherapeutic doses.

Cite This Article

APA
Hagedorn HW, Zuck S, Schulz R. (1996). Prothipendyl: detection and elimination in the horse–a case report. Dtsch Tierarztl Wochenschr, 103(4), 125-127.

Publication

ISSN: 0341-6593
NlmUniqueID: 7706565
Country: Germany
Language: English
Volume: 103
Issue: 4
Pages: 125-127

Researcher Affiliations

Hagedorn, H W
  • Institute of Pharmacology, Toxicology, and Pharmacy, Veterinary Faculty, University of Munich.
Zuck, S
    Schulz, R

      MeSH Terms

      • Animals
      • Antipsychotic Agents / analysis
      • Antipsychotic Agents / pharmacokinetics
      • Antipsychotic Agents / pharmacology
      • Behavior, Animal / drug effects
      • Doping in Sports
      • Female
      • Gas Chromatography-Mass Spectrometry / veterinary
      • Horses / metabolism
      • Horses / physiology
      • Reference Standards
      • Thiazines / analysis
      • Thiazines / pharmacokinetics
      • Thiazines / pharmacology
      • Triflupromazine / analysis

      Citations

      This article has been cited 1 times.
      1. Morak-Młodawska B, Jeleń M, Pluta K. Phenothiazines Modified with the Pyridine Ring as Promising Anticancer Agents. Life (Basel) 2021 Mar 5;11(3).
        doi: 10.3390/life11030206pubmed: 33807874google scholar: lookup