Innocently Exceeding Thresholds: Urinary Concentration of Salbutamol under SULT Inhibition

Code: 22C04MP

The anti-asthmatic drug salbutamol is prohibited in sports due to its activity as beta-2-sympathomimetic. However, because of its valuable therapeutic use, inhalative administration that does not exceed 600 micrograms over 8 hours (1600 micrograms over 24 hours) is considered as non-prohibited, not even requiring a therapeutic use exception. A threshold for the urinary salbutamol (excreted unchanged or as glucuronide) is set in doping control samples for discrimination of therapeutic and non-therapeutic use, if not proven differently.

As salbutamol is also excreted as sulfoconjugate, drugs interfering with human sulfotransferase enzymes may result in an alteration of the metabolite profile and thereby in an increased concentration of non-sulfonated salbutamol. One of these drugs that is considered to interfere with salbutamol metabolism is the pain killer etoricoxib. An influence of a con-administration with inhaled salbutamol will therefore be studied in human volunteers. Urinary concentrations will be monitored and compared in a paired design to evaluate exceeding threshold levels. For future detection of etoricoxib as potentially confounding factor its detectability in urine will also be studied. As etoricoxib is reported to be excreted mainly oa oxidized metabolites (only minor amounts unchanged), its main metabolites will be targeted as well. Future studies may also evaluate the influence on the excretion of sulfoconjugates of other drugs and excedding threshold or reporting limits to support data interpretation in doping control.