The practice of enhancing athletic performance through foreign substances was known from the earliest Olympic games. In 1967, the International Olympic Committee (IOC) established a Medical Commission responsible for developing a list of prohibited substances and methods. Drug tests were first introduced at the Olympic winter games in Grenoble and at the summer games in Mexico City in 1968. In February 1999, the IOC convened the World Conference on Doping in Sport in Lausanne, Switzerland. The Lausanne Declaration on Doping in Sport recommended creation of an International Anti-Doping Agency. The World Anti-Doping Agency (WADA) was formed in Lausanne, Switzerland on the basis of equal representation from the Olympic movement and public authorities. One of the mandates of WADA was to harmonize the Olympic antidoping code and develop a single code applicable and acceptable for all stakeholders. The world antidoping code developed by WADA included creation of several international standards (IS). The purpose of each IS was harmonization among antidoping organizations. The ISs were developed for laboratories, testing, the prohibited list, and for therapeutic use exemptions (TUE). The objective of this manuscript is to present a brief history of doping in sport and describe creation of WADA in 1999. The components of the World Anti-Doping code (in particular, the Therapeutic Use Exclusion program or TUE) is described. The WADA code defines a TUE as "permission to use, for therapeutic purposes, a drug or drugs which are otherwise prohibited in sporting competition." Experiences of the Canadian Centre for Ethics in Sport Doping Control Review Board are presented because this national TUE committee has been operational for over 12 years. The challenge of developing a rigorous global antidoping program requires acceptance of doping as a problem by sport organizations, athletes, and public authorities. Individual stakeholders must be prepared to preserve the values of sport, which means free from doping. This will require vigilance by all interested parties for the benefit of elite athletes and society overall.
To investigate the population pharmacokinetics of mycophenolic acid (MPA) in adult kidney transplant recipients during the crucial first week after transplantation.
Data were collected from 117 patients. MPA plasma concentrations were determined at t=0, 1, 2, 3 and 4 h after mycophenolate mofetil dosing on days 3, 5 and 7. Population analysis was performed using NONMEM. Covariates screened were sex, age, body weight, serum creatinine, creatinine clearance, serum albumin, days of therapy, diabetes mellitus, organ source (live or cadaveric) and co-therapy (tacrolimus or cyclosporine). Final model validity was evaluated using 200 boot strapped samples from the original data. Bias and precision were determined through comparison of observed and predicted concentrations.
Individual concentration-time profiles showed evidence of an absorption lag time and enterohepatic recirculation of MPA in some patients on some occasions. The best base model had bi-exponential elimination with a typical population (SE%) apparent clearance (CL/F) of 29 l/h (5%) and apparent volume of the central compartment of 65 l (7%). CL/F decreased significantly with increasing serum albumin (1.42 l/h reduction in total plasma CL/F with each 1 g/l increase in albumin) and was 27% greater in patients receiving cyclosporine than in those receiving tacrolimus. Evaluation of the final model showed close agreement between pairs of boot strapped and final model parameter estimates (all differences
The Correctional Service of Canada implemented a urine drug-testing program over a decade ago. Offenders residing in federal correctional institutions and living in the community on conditional release were subject to urine drug testing. The objective of this study is to describe this testing program and the extent of drug use by conditional release offenders in 2000. Urine specimens were tested for drugs of abuse and prescription drugs including amphetamines, cannabinoids, cocaine metabolite, opiates, phencyclidine, benzodiazepines, methyl phenidate, meperidine, pentazocine and fluoxetine by immunoassay screening followed by GC-MS confirmation. Ethyl alcohol was analyzed when specifically requested. Alternative screening and confirmation methods with lower cut-off values were used whenever urine specimens were dilute (creatinine