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Concentrations of caffeine, theophylline and theobromine in plasma and urine of dogs after application of coffee, tea and chocolate and its relevance to doping
Abstract
The methylxanthines caffeine, theophylline and theobromine are frequently detected in doping samples of racing greyhounds leading to the disqualification of the animal and possibly further penalties of the owner. The present study demonstrates that after application of coffee and tea to dogs caffeine, theophylline and theobromine can be found in plasma and urine. After feeding of cocoa products (chocolate) theobromine was the predominant methylxanthine to be analysed. Therefore the quantitative relationship of the various methylxanthine metabolites detected can indicate the origin of the ingested methylxanthines. In order to avoid violation of doping regulations, dog owners should assure that their animals have no access to methylxanthine-containing diets in the days before racing competitions. Furthermore the results indicate, that by the uptake of products which are rich in theobromine such as cocoa powder or cooking chocolate toxic to lethal plasma concentrations of this methylxanthine can be attained.
... Due to its long half-life, theobromine remains in the bloodstream for a longer period of time, which may result in symptoms from high doses persisting for several days. Furthermore, caffeine is metabolised to theobromine, reaching its peak plasma concentration approximately 6 to 8 hours' postconsumption (Loffler et al., 2000a;2000b). The metabolism of both methylxanthines occurs in the liver, followed by excretion through the bile ducts and go through enterohepatic circulation (Dolder, 2013). ...
A seven years old Rottweiler dog was presented to Veterinary Clinical Complex, College of Veterinary and Animal Sciences, Kishanganj, Bihar, in lateral recumbency with a history of anorexia, vomiting and diarrhea (loose stool) over the previous two days. History taking revealed excessive consumption of chocolates (both milk chocolate and dark chocolate) by the dog two days earlier. The case was clinically diagnosed as chocolate toxicity. Tachycardia with arrythmia and tachypnea were noticed on cardiac and lung auscultation, respectively. The dog was treated with Normal saline solution, Propranolol hydrochloride, Ondansetron, Ranitidine hydrochloride, Cefotaxime and Vitamin B complex. Complete clinical recovery was observed after 3rd day of treatment. It has been concluded that such cases of chocolate toxicity can be successfully managed with appropriate supportive treatment and diligent monitoring of the patient.
... Theobromine, on the other hand, is absorbed more slowly compared to caffeine (maximum plasma concentration after about 2 hours). Furthermore, caffeine is metabolised to theobromine (maximum plasma concentration after 6 to 8 hours) (Löffler et al. 2000a(Löffler et al. , 2000b. Both methylxanthines are metabolised in the liver, excreted via the bile ducts and undergo enterohepatic circulation (Dolder 2013). ...
Objectives
To describe the clinical features and outcome of dogs after chocolate ingestion.
Material and Methods
Retrospective evaluation of clinical signs, clinical pathological findings, therapy and outcome of 156 dogs after chocolate ingestion. The concentration of methylxanthines (theobromine, caffeine) was calculated based on the type of chocolate and the amount ingested.
Results
One hundred and twelve dogs had no clinical signs. Forty‐four dogs had clinical signs of chocolate intoxication. Twenty‐eight of these 44 dogs ingested dark and bitter chocolate. Reasons for presentation were agitation (33), tremor (22), vomiting (21), panting (11), polyuria/polydipsia (seven) and diarrhea (two). Common clinical findings were sinus tachycardia (28), tachypnea/panting (14), hyperthermia (10) and dehydration (seven). Clinical pathological findings in 34 of 44 dogs consisted of hyperlactataemia (23), hypokalaemia (16), mild hyperglycaemia (16) and mild alanine aminotransferase (ALT) and aspartate aminotransferase (AST) elevation (14). After decontamination (apomorphine, activated carbon) and symptomatic treatment (fluid therapy, esmolol, forced diuresis, sedatives), 43 of the 44 dogs survived.
Clinical Significance
In dogs with potential chocolate intoxication, the type and amount of chocolate and the time of ingestion are important factors. Cardiovascular, neurological and gastrointestinal signs are the most common clinical signs. In this case series, the prognosis after decontamination and symptomatic therapy was good, with a mortality rate of less than 3%.
... Moreover, like many other drugs, toxins and trace elements and/or their metabolites, theobromine can also be detected in equine hair as a means for assessing drug history (Dunnett and Lees 2003). Whilst methylxanthine doping is also an issue in greyhound racing (Wells et al. 1988;Loeffler et al. 2000) it would be interesting to see if the relevant sports organisations will follow the example of the World Anti-Doping Agency of moving caffeine from the "Prohibited List" to the "Monitoring Program" for detecting patterns of misuse rather than imposing a ban. The reasons for this change include (1) the presence of a great interperson variability in caffeine metabolism, (2) the notion that above the traditionally used 12 mg/ml threshold level, caffeine has a detrimental effect on performance, but also (3) that lowering the detection threshold increases the risk of being penalised for consuming caffeine through everyday food and drink (WADA 2008). ...
The effects of theobromine in man are underresearched, possibly owing to the assumption that it is behaviourally inert. Toxicology
research in animals may appear to provide alarming results, but these cannot be extrapolated to humans for a number of reasons.
Domestic animals and animals used for racing competitions need to be guarded from chocolate and cocoa-containing foods, including
foods containing cocoa husks. Research ought to include caffeine as a comparative agent, and underlying mechanisms need to
be further explored. Of all constituents proposed to play a role in our liking for chocolate, caffeine is the most convincing,
though a role for theobromine cannot be ruled out. Most other substances are unlikely to exude a psychopharmacological effect
owing to extremely low concentrations or the inability to reach the blood–brain barrier, whilst chocolate craving and addiction
need to be explained by means of a culturally determined ambivalence towards chocolate.
KeywordsChocolate-Cocoa-Comparative-Craving-Liking-Myths-Pharmacology-Psychology-Theobromine-Toxicology
... Moreover, like many other drugs, toxins and trace elements and/or their metabolites, theobromine can also be detected in equine hair as a means for assessing drug history (Dunnett and Lees 2003). Whilst methylxanthine doping is also an issue in greyhound racing (Wells et al. 1988;Loeffler et al. 2000) it would be interesting to see if the relevant sports organisations will follow the example of the World Anti-Doping Agency of moving caffeine from the "Prohibited List" to the "Monitoring Program" for detecting patterns of misuse rather than imposing a ban. The reasons for this change include (1) the presence of a great interperson variability in caffeine metabolism, (2) the notion that above the traditionally used 12 mg/ml threshold level, caffeine has a detrimental effect on performance, but also (3) that lowering the detection threshold increases the risk of being penalised for consuming caffeine through everyday food and drink (WADA 2008). ...
The effects of theobromine in man are underresearched, possibly owing to the assumption that it is behaviourally inert. Toxicology research in animals may appear to provide alarming results, but these cannot be extrapolated to humans for a number of reasons. Domestic animals and animals used for racing competitions need to be guarded from chocolate and cocoa-containing foods, including foods containing cocoa husks. Research ought to include caffeine as a comparative agent, and underlying mechanisms need to be further explored. Of all constituents proposed to play a role in our liking for chocolate, caffeine is the most convincing, though a role for theobromine cannot be ruled out. Most other substances are unlikely to exude a psychopharmacological effect owing to extremely low concentrations or the inability to reach the blood-brain barrier, whilst chocolate craving and addiction need to be explained by means of a culturally determined ambivalence towards chocolate.
Methylxanthines are often used as stimulants of the central nervous system, of the cardiovascular system and as bronchodilators. In this study the pharmacokinetics of caffeine, theophylline and theobromine in dogs were examined. After oral application of caffeine and theophylline (10 mg/kg) highest plasma concentrations of caffeine were about 61.8 μmol/l and of theophylline about 42.5 μmol/l after 1.6 and 4.8 hours, respectively. The elimination half-lives for both methylxanthines were 3.2 hours and, therefore, effective plasma concentrations were maintained for several hours. In the urine the methylxanthines administered could also be detected, after application of caffeine its metabolite theobromine reached high concentrations.
The pharmacokinetics of caffeine (CAF) and its metabolites, dimethylxanthines, were examined in horses administered 2.5 mg/kg of CAF intravenously (i.v.), intramusculary (i.m.), or orally (p.o.). The plasma samples were extracted by Extrelut and the concentrations of CAF and metabolites were determined by high performance liquid chromatography (HPLC) with a short column. The pharmacokinetics of CAF after bolus i.v. injection were described by the assumption of a two-compartment model, and those of CAF after i.m. or p.o. administration were done by the assumption of a one-compartment model. The biologic half lives of CAF were 15.5, 18.6, and 16.4 h after administering i.v., i.m. and p.o., respectively. The extent of the bioavailability of the p.o. administration was determined as 1.04 times the dose. The differences in pharmacokinetic parameters were not statistically significant among administration routes. A straight correlation existed between the logarithms of body weights of different species of animals and those of their biologic half lives of CAF. Therefore, the biologic half life of CAF in an animal might be predictable as a function of its body weight.
Results of urine drug analyses for three racing greyhounds that tested positive for caffeine in this laboratory were contested
by the animal trainer, who asserted that positives were achieved from deliberate chocolate feeding by a rival kennel. The
metabolism and excretion of methyixanthinea was examined by high-performance liquid chromatography of extracts of the urine
of racing greyhounds force-fed either caffeine (No Doz™) or chocolate (Hersheys™ chocolate drops). Samples from untreated
animals served as controls. Study results showed that test animals fad chocolate could be very easily distinguished from those
fed caffeine. While the former animals exhibited a prominent theobromine peak with trace amounts of caffeine and theophylline,
the caffeine-treated animals gave a prominent caffeine peak with moderate theophylline levels and almost nondetectable theobromine
amounts. When these results were compared with the results from the positive authentic racing animals, chocolate feeding was
clearly ruled out as an alternative to caffeine administration.