This letter is being written with regard to the work conducted by the Association of Inhalation Toxicologists Working Party in attempts to standardize the calculation of delivered dose in nonclinical aerosol inhalation studies (Alexander et al., Association of Inhalation Toxicologists (AIT) Working Party Recommendation for Standard Delivered Dose Calculation and Expression in Nonclinical Aerosol Inhalation Toxicology Studies with Pharmaceuticals, Inhal. Toxicol., 20(13): 1179–1189). The members of this group should be commended for their contributions. They conducted a thorough review of a very large data set and provided scientifically backed conclusions that, if used by the entire preclinical inhalation drug delivery field, would unify the calculation and reporting of delivered dose or deposited dose.
While the work by this group is scientifically justified, the guidance to shift from the current model may be premature or unwarranted unless justified for each particular case. In order to verify the merit of establishing the new equation for RMV, an evaluation of the average absolute error between the Bide and AIT equation should have been conducted to ensure they are adequately different. An example of this type of evaluation was conducted by Machatha et al. (2005), in Int. J. Pharm. 294:185–192. We conducted an analysis of this type on the data reported by AIT, and our analysis indicates the only statistical difference between these two equations is in the male and female dogs. The variability shows that there was no statistical difference in mice, rats, and/or nonhuman primates. Thus, the AIT equation performs the same as the Bide equation except in the case of dogs.
Regardless, the recommendations reached by this working party hold true: that dose calculation should be based on the dose equation that the RMV can be calculated with either AIT or Bide’s formula, that any assumption for IF should be clearly stated, and that a delivered dose should be normalized.
Regards,
Philip Kuehl, PhD
Associate Research Scientist
Lovelace Respiratory Research Institute
Albuquerque, New Mexico, USA