Contamination and carry-over in clinical pharmacokinetic trials with aerosolized budesonide

Background: Contamination and carry-over by active drug components is a major issue, especially in pharmacokinetic studies carried out with aerosolized substances. Measures to avoid contamination and carry-over in blood samples remain poorly standardized and validated. Objective: To investigate the space- and time-related distribution pattern of budesonide aerosolized via MDI. Methods: A matrix of crystallization dishes was set up in a measurement chamber. One puff of budesonide MDI (184 μg emitted dose, 200 μg nominal dose) was aerosolized and aerosol was allowed to sediment for 0.25 to 6.5 hours. Recovery of budesonide in the crystallization dishes was measured via HPLC and correlated to time course and spatial matrix. Results: In 1 m distance of actuating the MDI, a mean recovery of budesonide of 0.688 μg after 0.25 hours and 1.423 μg after 6.5 hours was observed. The surface concentration in 1 m distance was 9.7 ng/cm 2 after 0.25 hours and 20.1 ng/cm 2 after 6.5 hours. Conclusion: This study is a valid basis for risk assessment of carry-over effects in clinical trials with aerosolized drugs. Regarding surface concentrations in the nanogram range as shown in our study compared to serum drug concentrations in the picogram range as determined in pharmacokinetic trials, carry-over effects via aerosols seem probable. Further studies to determine the extent and origin of these effects will therefore be performed.