Cocaine metabolism and urinary excretion after different routes of administration / Edward J. Cone, Abraham Tsadik, Johnathan M. Oyler, William D. Darwin

• Therapeutic Drug Monitoring 20 (1998) 5 (October), p. 556-560
• PMID: 9780135
• DOI: 10.1097/00007691-199810000-00019

Abstract

Cocaine abusers frequently self-administer cocaine by different routes of administration. A controlled-dosing study was performed to assess the effect of different routes of administration on the excretion profile of cocaine and metabolites in urine. Single bioequivalent doses of cocaine were administered by the intravenous, intranasal, and smoked routes to six human subjects. Urine specimens were collected for 3 days after drug administration and were analyzed for cocaine, metabolites, and anhydroecgonine methyl ester, the thermal degradation product of cocaine, by gas chromatography-mass spectrometry. Cocaine was rapidly absorbed, metabolized, and excreted in urine. Peak cocaine concentrations were generally present in the first specimen collected; thereafter, concentrations declined quickly and were usually below the limit of detection (approximately 1 ng/ml) within 24 hours. The metabolite benzoylecgonine was present in the highest concentration and represented approximately 39%, 30%, and 16%, of the administered dose by the intravenous, intranasal, and smoked routes, respectively. Combined amounts of ecgonine methyl ester and six minor metabolites (norcocaine, benzoylnorecgonine, m-hydroxycocaine, p-hydroxycocaine, m-hydroxybenzoylecgonine, and p-hydroxybenzoylecgonine) accounted for approximately 18%, 15%, and 8% of the administered dose by the intravenous, intranasal, and smoked routes, respectively. Anhydroecgonine methyl ester was present in trace amounts (0.02% dose) in specimens collected after smoked cocaine administration. Because many of these metabolites exhibit pharmacologic activity, their presence in urine may indicate that they play complex biologic roles in the overall activity of cocaine.

CAS ad hoc Division (O.G. Nagano) 98/002 R. / International Olympic Committee (IOC)
CAS 1998 NAG 2 Ross Rebagliati vs International Olympic Committee (IOC)

Disqualification of an athlete for use of marijuana
Lack of legal basis to sanction the athlete

1. The sole basis to sanction the use of marijuana at the Olympic Games is Chapter II, article III, paragraph B of the IOC Medical Code, which treats the use of marijuana as doping only if there is an agreement between the IOC and the relevant international federation to that effect. Absence of any such agreement in this case.

2. The CAS recognizes that from an ethical and medical perspective, cannabinoids consumption is a matter of serious social concern. The CAS is not, however, a criminal court and can neither promulgate nor apply penal laws. The CAS must decide within the context of the law of sports, and cannot invent prohibitions or sanctions where none appear.

In February 1998 the Athlete Ross Rebagliati competed in the Canadian Men’s snowboard giant slalom during the Nagano 1998 Olympic Winter Games where he won the Olympic gold medal.

On 11 February 1998 the International Olympic Committee (IOC) has reported an anti-doping rule violation against the Athlete after his sample tested positive for the substance marijuana (cannabis).
Therefore the IOC Executive Board decided to rescind the Olympic gold medal due to the positive doping test.

Hereafter the Athlete appeals the IOC Executive Board decision with the ad hoc Division of the Court of Arbitration for Sport (CAS) present at the Nagano 1998 Olympic Winter Games.
The Athlete stated he did not use cannabis since April 1997 and argued that the positive test was the result of second hand cannabis smoke due to he attended two parties in January 1998 where people smoked cannabis.
The CAS Panel concludes that the sanction against the Athlete lack requisite legal foundation, due to marijuana (cannabis) wasn't actually on the IOC banned-substance list.

The ad hoc Division of the Court of Arbitration for Sport Panel decides:

1.) The IOC Executive Board's decision of 11 February 1998 is reversed.
2.) No costs are awarded.
3.) The decision shall be subject to immediate publication.

Cannabis has since been listed by the World Anti-Doping Agency (WADA) as a banned substance.

TAS 98/189 Michael Dionne and US Bobsled & Skeleton Federation (USBSF) vs. Fédération Internationale de Bobsleigh et de Tobogganing (FIBT)

Facts
Michael Dionne, appellant and the United States Bobsled and Skeleton Federation (USBSF) appeal against the decision of the executive committee of the International Bobsleigh and Tobogganing Federation (FIBT). Appellant had been sanctioned with a period of ineligibility of three months for being positive tested for the prohibited substance ephedrine (A and B sample). The reason was the use of products against a cold which contained the prohibited substance. Appellant appealed because he believes the sanction was too harshly and he wanted to have the opportunity to take part in the Olympic Games of Nagano.

History
The representative of the appellant took the position that the three month suspension would violate:
- the International Olympic Committee (IOC) Medical code,
- the FIBT's own rules, and
- principles of fairness and proportionality reflected in previous decisions of the CAS.
The FIBT maintains that the appeal must fail because appellant didn't exhausted internal remedies within the FIBT rules. However the arbitrator remarks that it may be useful for the FIBT to reexamine and clarify its own procedure for appeals.
The arbitrator considers the penalty put upon the appellant and concludes that it was the lowest possible.
I was taken in consideration that the appellant wasn't cheating but careless towards the use of supplements.

Decision
1. The FIBT decision regarding appellant is upheld.
2. In the circumstances, the sanction thus confirmed is not considered to affect the status of appellant as an accredited member of the U.S. Olympic Team.
3. The application has not occasioned significant costs. There is no award in that regard.
4. This award shall immediately be made public.

1998 List of Prohibited Classes of Substances and Prohibited Methods / IOC Medical Commission. – International Olympic Committee (IOC), 1998

INTERNATIONAL OLYMPIC COMMITTEE MEDICAL CODE

PROHIBITED CLASSES OF SUBSTANCES AND PROHIBITED METHODS

31st January 1998

I. PROHIBITED CLASSES OF SUBSTANCES
A. Stimulants
B. Narcotics
C. Anabolic Agents
D. Diuretics
E. Peptide and glycoprotein hormones and analogues

II. PROHIBITED METHODS
A. Blood doping
B. Pharmacological, chemical and physical manipulation

III. CLASSES OF DRUGS SUBJECT TO CERTAIN RESTRICTIONS
A. Alcohol
B. Marijuana
C. Local anaesthetics
D. Corticosteroids
E. Beta-blockers

SUMMARY OF IOC REGULATIONS FOR DRUGS WHICH NEED THE WRITTEN NOTIFICATON OF A PHYSICIAN

SUMMARY OF URINARY CONCENTRATIONS ABOVE WHICH IOC ACCREDITED LABORATORIES MUST REPORT FINDINGS FOR SPECIFIC SUBSTANCES

LIST OF EXAMPLES OF PROHIBITED SUBSTANCES

Source: Bibliothèque du CIO / IOC Library

Androstanediol and 5-androstenediol profiling for detecting exogenously administered dihydrotestosterone, epitestosterone, and dehydroepiandrosterone : potential use in gas chromatography isotope ratio mass spectrometry / Cedric H.L. Shackleton, Esther Roitman, Andy Phillips, Tony Chang. - (Steroids 62 (1997) 10 (October); p. 665-673)

• PMID: 9381514
• DOI: 10.1016/s0039-128x(97)00065-2

Abstract

The basis of a potential method for confirming intake of four natural androgens (testosterone, epitestosterone, dihydrotestosterone, and dehydroepiandrosterone is presented. The method relies on isolating from urine a steroid fraction containing androstenediol and androstanediol metabolites of these natural steroids and analyzing their 13C content by gas chromatography, combustion, isotope ratio mass spectrometry. The steroids were recovered from urine by conjugate hydrolysis with a Helix pomatia preparation (sulfatase and beta-glucuronidase), Girard T reagent separation to obtain a nonketonic fraction, and Sephadex LH-20 chromatography for purification. Metabolites appropriate for all of the natural steroids could be separated (as diacetates) by gas chromatography on a DB-17 capillary column viz.: 5 alpha (and beta)-androstane-3 alpha,17 alpha-diol (epitestosterone as precursor); 5 alpha (and beta)-androstane-3 alpha,17 beta-diol (testosterone as precursor); 5-androstene-3 beta,17 beta-diol (dehydroepiandrosterone precursor); and 5 alpha-androstane-3 alpha,17 beta- (and 17 alpha-) diol (dihydrotestosterone precursor). Measurement of the 13C content of the specific analytes after ingestion of the androgen precursors demonstrated a lowering of delta 13C/1000 value compared to normal values. Typically, in the male individual studied, delta 13C/1000 values for all components were -26 to -27 before drug administration and -29 to -30 at 6 h after, the latter values reflecting those obtaining for commercial synthetic steroid compared to in vivo synthesized steroid. While generally the metabolism of the steroids was as expected, this was not the case for 5 alpha-dihydrotestosterone. A major metabolite was 5 alpha-androstane-3 alpha,17 alpha-diol, which had presumably been formed by 17 beta/17 alpha isomerization, a process previously known for unnatural anabolics but not for natural hormones. The isolation, purification, and isotope ratio mass spectrometry techniques described may form the basis of a general method for confirming natural steroid misuse by sports participants.

Confirming testosterone administration by isotope ratio mass spectrometric analysis of urinary androstanediols / Cedric H. Shackleton, Andy Phillips, Tony Chang, Ye Li. - (Steroids 62 (1997) 4 (April); p. 379-387)

• PMID: 9090799
• DOI: 10.1016/s0039-128x(96)00253-x

Abstract

A gas chromatographic combustion isotope ratio mass spectrometric (GC/C/IRMS) method was used for studying the incorporation of exogenous testosterone enanthate into excreted urinary 5 alpha- and 5 beta-androstane-3 alpha, 17 beta-diols. A multistep but straightforward work-up procedure produced a simple GC chromatogram of urinary steroid acetates composed principally of two androstanediols and pregnanediol. It is anticipated that such a method may form the basis of a doping control test for testosterone that could be used as a primary method during major sporting events or alternatively as a verification technique. Urine samples from five individuals were collected before and after administration of testosterone enanthate (250 mg). The delta 13C0/1000 value of andro-stanediols was around -26 to -28 during the baseline period and decreased to about -29 to -30 in the days following synthetic testosterone administration. One of the other major steroids in the chromatogram, pregnanediol, was utilized as the "internal standard," because its delta 13C0/1000 values did not markedly change following testosterone administration, remaining at -25 to -27. In all subjects studied, the delta 13C0/1000 values for androstanediols were reduced sufficiently over 8 days to confirm administration of synthetic testosterone. Although steroids isolated from urine of normal individuals from 12 different countries gave values between -24 and -28, this seemed not to be related to nationality or region. The most likely variable is the proportion of plants with low and high carbon 13 content in the diet. This variable is likely to be more affected by individual food preferences than broad ethnic food divisions. In this paper, we propose a ratio of delta 13C0/1000 for androstanediols to pregnanediol as a useful discriminant of testosterone misuse, a value above 1.1:1.0 being indicative of such misuse. The work-up procedure was designed for batch analysis and to use only simple techniques, rather than employ further instrumentation, such as high-performance liquid chromatography (HPLC), in purifying steroids for GC/C/IRMS.

Growth hormone-releasing peptides and their analogs / F. Camanni, E. Ghigo, E. Arvat

• Frontiers in neuroendocrinology 19 (1998) 1 (January); p. 47-72
• PMID: 9465289
• DOI: 10.1006/frne.1997.0158

Abstract

Growth hormone-releasing peptides (GHRPs) are a series of hepta (GHRP-1)- and hexapeptides (GHRP-2, GHRP-6, Hexarelin) that have been shown to be effective releasers of GH in animals and humans. More recently, a series of nonpeptidyl GH secretagogues (L-692,429, L-692,585, MK-0677) were discovered using GHRP-6 as a template. Some cyclic peptides as well as penta-, tetra-, and pseudotripeptides have also been described. This review summarizes recent developments in our understanding of the GHRPs, as well as the current nonpeptide pharmacologic analogs. GHRPs and their analogs have no structural homology with GHRH and act via specific receptors present at either the pituitary or the hypothalamic level. The GHRP receptor has recently been cloned and it does not show sequence homology with other G-protein-coupled receptors known so far. This evidence strongly suggests the existence of a natural GHRP-like ligand which, however, has not yet been found. Although the exact mechanism of action of GHRPs has not been fully established, there is probably a dual site of action on both the pituitary and the hypothalamus, possibly involving regulatory factors in addition to GHRH and somatostatin. Moreover, the possibility that GHRPs act via an unknown hypothalamic factor (U factor) is still open. The marked GH-releasing activity of GHRPs is reproducible and dose-related after intravenous, subcutaneous, intranasal, and even oral administration. The GH-releasing effect of GHRPs is the same in both sexes, but undergoes age-related variations. It increases from birth to puberty and decreases in aging. The GH-releasing activity of GHRPs is synergistic with that of GHRH and not affected by opioid receptor antagonists, while it is only blunted by inhibitory influences that are known to nearly abolish the effect of GHRH, such as neurotransmitters, glucose, free fatty acids, glucocorticoids, rhGH, and even exogenous somatostatin. GHRPs maintain their GH-releasing effect in somatotrope hypersecretory states, such as acromegaly, anorexia nervosa, and hyperthyroidism. On the other hand, GHRPs and their analogs have been reported to be effective in idiopathic short stature, in some situations of GH deficiency, in obesity, and in hypothyroidism, while in patients with pituitary stalk disconnection and in Cushing's syndrome the somatotrope responsiveness to GHRPs is almost absent. A potential role in the treatment of short stature, aging, catabolic states, and dilated cardiomyopathy has been envisaged.

L'image du mois. Acne gymnasium : une acne fulminante dopee = Image of the month. Gymnasium acne: a fulminant doping acne / Gérald Pierard. - (Revue Médicale de Liège 53 (1998) 8 ; p. 441-443)

• PMID: 9810201

Key words:

• Acne Vulgaris/chemically induced/pathology ;
• Adult ;
• Anabolic Agents/adverse effects ;
• Doping in Sports ;
• Humans ; Male ;
• Nandrolone/adverse effects/analogs & derivatives ;
• Weight Lifting

Handel in doping : een verkennend ondezoek naar de handel in dopinggeduide middelen in Nederland / A.W.A. Koert, R. van Kleij. - i.o.v. het Nederlands Centrum voor Dopingvraagstukken (NeCeDo). - Nieuwegein, Arko Uitgeverij, 1998. - ISBN 9072047435

Doping Trade : a pilot study into the trade in doping substances in the Netherlands / A.W.A. Koert, R. van Kleij. - Netherlands Centre for Doping Affairs (NeCeDo). - Nieuwegein, Arko Publisher, 1998. - ISBN 9072047435

Naar aanleiding van met name de gesprekken met respondenten afkomstig uit de cosmetische sport, wordt geconcludeerd dat de situatie met betrekking tot het gebruik van dopinggeduide middelen om drie redenen zorgwekkend genoemd moet worden. Allereerst blijkt het gebruik ervan zich in de loop der jaren te hebben uitgebreid naar groepen die voorheen niet hun toevlucht tot deze middelen namen. De tweede reden is gelegen in feit dat er sneller dan vroeger naar dopinggeduide middelen gegrepen wordt, er hogere doseringen worden gebruikt evenals riskantere middelen.
In dit verband wordt door de betreffende respondenten gesproken over een 'pilmentaliteit'. De derde reden tot zorg is de toename van het aantal vervalsingen op de markt voor dopinggeduide middelen, en de daarmee gepaard gaande afname van de kwaliteit.
Dezelfde conclusie dient getrokken te worden naar aanleiding van wat bekend is geworden omtrent de handel in deze middelen. Hier kan geconcludeerd worden, dat er sprake is van een uitgebreid nationaal en internationaal netwerk dat zich bezighoudt met de handel in en de productie van dopinggeduide middelen. In dit netwerk doen zich nieuwe risicovolle ontwikkelingen voor. Daarmee wordt enerzijds gedoeld op de mate waarin het netwerk zich vervlecht met andere criminele netwerken en de daarmee gepaard gaande verschijnselen (bedreigingen, intimidaties, afrekeningen).
Daarnaast daalt, zoals al gezegd, hierdoor de kwaliteit van de verhandelde producten op de zwarte markt.

Inhoud:

1.) Doping in historisch perspectief
2.) Probleemstelling
3.) Methode van onderzoek
- 1. Inleiding
- 2. Het verkrijgen van het onderzoeksmateriaal
4.) Dopinggeduide middelen
- 1. Inleiding
- 2. Anabole androgene steroïden
- 3. Middelen om de bijwerkingen van anabole steroïden te onderdrukken
- 4. Afslankmiddelen
- 5. Middelen, die de werking van anabole steroïden versterken
- 6. Overige middelen
- 7. Samenvatting
5.) Gebruikers
- 1. Inleiding
- 2. Gebruik in de topsport versus gebruik in het sportschoolcircuit
- 4. Indeling van dopinggebruikers in het sportschoolcircuit
- 3. Hoe worden cosmetische sportrs gebruikters?
- 5. Tendensen in het gebruik
- 6. Conclusie en samenvatting
6.) Dopinghandelaren
- 1. Inleiding
- 2. Indeling van dopinghandelaren
- 3. Bronnen 85
- 4. Economische aspecten van de dopinghandel
- 5. Handel in dopinggeduide middelen via Internet
- 6. Samenvatting van het hoofdstuk
7.) Conclusies
8.) Aanbevelingen

AUSTRALIAN SPORTS DRUG AGENCY 1996-97 ANNUAL REPORT
© Commonwealth of Australia
ISSN 1037-378

Tabel of contents
The structure of this report iv
Compliance index v
Abbreviations ix
Chairman's Introduction x
Board of Directors xii

Chapter 1
Corporate overview
Legislative basis
Responsible Minister
Our mission and values.
Sharpening our focus 2
Our partners 3
Social justice and equity 4
Discretionary grants 4
Internal and external scrutiny 4

Chapter 2
Critical Success Factor One: Deterence 7
Objective 1
Objective 2
Objective 3
Increase the perceived risk of being selected for a drug test 9
Increase the standard of drug testing and sample collection procedures 17
Increase the comprehensive nature of the response by sports
to banned doping practices 24

Chapter 3
Critical Success Factor Two: Education 29
Objective 4: Increase the perception that banned doping practices are cheating 30
Objective 5: Increase the skills and knowledge of government and
non-government clients 32
Objective 6: Increase the knowledge of athletes and coaches of the international
response to drugs in sport 36
Objective 7: Increase the sporting community's awareness of ASDA activities 37

Chapter 4
Critical Success Factor Three: International Response 39
Objective 8: ncrease the effectiveness of international anti-doping programmes 40
Objective 9: Increase the skills and knowledge of international clients 44

Chapter 5
Critical Success Factor Four: National Response 51
Objective 10: Increase the effectiveness of the national response to the drugs in sport issue 52

Chapter 6
Critical Success Factor Five: Client Participation 55
Objective 11: Increase the effectiveness of client involvement in planning, implementation and evaluation of agency activities 56

Chapter 7
Critical Success Factor Six: Efficiency and Accountability 61
Objective 12: Increase the effectiveness of systems and structures to enable staff to meet their responsibilities 62
Objective 13: Increase the skills of staff to meet agency's requirements 69
Objective 14: Increase the effectiveness of the planning and evaluation process 72

Chapter 8
Financial Statements 75
Independent audit report by the Australian National Audit Office 76
Statement by Directors 78
Operating statement for year ended 30 June 1997 79
Statement of assets and liabilities as at 30 June 1997 80
Statement of cash flows for the year ended 30 June 1997 81
Schedule of commitments for the year ended 30 June 1997 82
Schedule of contingencies for the year ended 30 June 1997 83
Notes to and forming part of the Financial Statements for the year ended 30 June 1997 84

Appendix 1 Objects, functions and powers of the Australian Sports Drug Agency as specified in the Australian Sports Drug Agency Act 1990 92
Appendix 2 Powers of the Minister under the Australian Sports Drug Agency Act 1990 94
Appendix 3 Summary of Entries on Register of Notifiable Events 1996-97 95
Appendix 4 ASDA testing for period 1 July 1996 to 30 June 1997 98
Appendix 5 ASDA user-pays testing for period 1 July 1996 to 30 June 1997 101
Appendix 6 Outcome of previous entries on Register of Notifiable Events for which sanctions were to be advised 103
Appendix 7 Summary of entries on Register of Notifiable Events by doping class and sport 1996-97 104
Appendix 8 Summary of entries on the Register of Notifiable Events 1991-92 to 1996-97 105
Appendix 9 Summary of entries on the International List of Incidences 1996-97 106
Appendix 10 Outcome of previous entries on the International List of Incidences for which sanctions were to be advised 106
Appendix 11 International Olympic Committee Medical Code - Prohibited classes of substances and prohibited methods 107
Appendix 12 Implementation of the National Drugs in Sport Framework by states and territories; policy, educational, legislative and drug testing components 113
Index 115

Figures
Figure 1.1 Australian Sports Drug Agency structure at 30 June 1997 2
Figure 2.1 Drug testing conducted 1992-93 to 1996-97 11
Figure 3.1 Comparison of hotline usage 33
Figure 3.2 Analysis of hotline queries 34
Figure 3.3 Handbook, hotline and Infopac distribution 35

Tables
Table 1.1 ASDA expenditure by programme 3
Table 1.2 ASDA financial and staffing resources summary 5
Table 6.1 Total number of employees at 30 June 1997 59