Theoretical relationship between the post-administration time and plasma or urinary concentration of a metabolite and the unchanged drug. Administration of caffeine to horses.
Abstract: In a doping test for racing horses, it is useful for the elucidation of the illegal use of drugs if one can estimate the time at which the detected drug was administered. In order to estimate the time which has elapsed after the administration of caffeine (CA) into horses, the ratios of concentration for the respective metabolites to the unchanged CA in the plasma or the urine were determined. These ratios have been known to be independent of the dose of CA. The relationship between [plasma or urinary concentration of a metabolite]/ [plasma or urinary concentration of the unchanged drug] and the post-administration time of CA was expressed in a theoretical equation using pharmacokinetic parameters. When CA was administered at 2.5 mg/kg intravenously, intramuscularly or orally, all of the experimentally observed values of plasma or urinary metabolites: theophylline, theobromine and paraxantine, agreed well with the theoretical formulas, indicating that there exists a theoretical relationship between the post-administration time and the concentration ratio of the respective metabolites to unchanged CA.
Publication Date: 1996-10-01 PubMed ID: 8913509DOI: 10.1248/bpb.19.1341Google Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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The researchers developed a theoretical equation to estimate the time since caffeine was administered to a horse, which uses the ratios of the concentrations of metabolites (broken-down caffeine) to unchanged caffeine in plasma or urine. They confirmed the accuracy of this method across multiple administration methods.
Theoretical Relationship Developed
- The aim of the research was to create a formula that could be used to estimate when a horse was given caffeine (CA), based on the amount of CA and its metabolites (the substances the body breaks CA down into) in the blood (plasma) or urine.
- These metabolite:CA ratios have previously been found to be consistent regardless of the original dose of CA given.
- By using various pharmacokinetic parameters (metrics which describe how the body absorbs, distributes, metabolizes, and excretes a substance), a theoretical relationship was developed. This formula expresses the post-administration time of CA in relation to the concentration of metabolites and unchanged CA in the horse’s plasma or urine.
Confirmation of the Developed Relationship
- Having developed their theoretical equation, the researchers tested it by administering CA to horses at a dose of 2.5mg/kg. This was done through intravenous, intramuscular, and oral routes.
- They then measured the concentrations of CA and its three primary metabolites (theophylline, theobromine, and paraxanthine) in the plasma or urine samples.
- They found that the experimentally observed values closely matched those predicted by their theoretical formulas. This strongly suggested that the post-administration time of CA can be accurately estimated from the concentration ratio of the metabolites to unchanged CA. This was true regardless of the method of administration.
Implications of the Study
- This method could be very useful for doping tests in horse racing.
- By providing an estimate of the time since CA administration, it could potentially help to identify illegal use of this substance.
Cite This Article
APA
Aramaki S, Ishidaka O, Suzuki E, Momose A, Umemura K.
(1996).
Theoretical relationship between the post-administration time and plasma or urinary concentration of a metabolite and the unchanged drug. Administration of caffeine to horses.
Biol Pharm Bull, 19(10), 1341-1346.
https://doi.org/10.1248/bpb.19.1341 Publication
Researcher Affiliations
- Laboratory of Racing Chemistry, Tokyo, Japan.
MeSH Terms
- Animals
- Caffeine / blood
- Caffeine / pharmacokinetics
- Caffeine / urine
- Horses / metabolism
- Substance Abuse Detection / methods
- Substance Abuse Detection / veterinary
- Theophylline / blood
- Theophylline / urine
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