Oral deposition

Closely related to an ability to analyze and to understand people is an instinctively curious mind. Both facilitate investigation and revelation of facts—an important function of any lawyer, which like other aspects increases in importance with increasing complexity of subject matter. Chemists inherently tend to be inquisitive. This trait will help the chemist-tumed-lawyer during interviewing of witnesses, examining of witnesses by oral depositions, or in open court. When cross-examining witnesses, he will follow the witness s mental processes, learn what he may be holding back, and perhaps extract testimony that will be helpful to the lawyers case. 

Pulmonary deposition efficiency Location of pulmonary deposition Pulmonary residence time (dissolution rate and other factors) Oral bioavailability Degree of oral deposition Systemic clearance Volume of distribution Protein binding... 

Clark et al. (40) developed what is a mathematically similar approach to Theil s, which was applied to both DPIs and pMDIs plus spacer and chambers. (Clark et al. deliberately avoided using data from pMDIs alone because of the difficulties associated with the ballistic nature of the plume.) The basis of the technique is the assumption that lung deposition is simply the inhaled dose minus that deposited in mouth and oropharynx. This approach does not require the application of a lung deposition model and is justified for most DPIs and pMDI since the fractions exhaled after a typical 5- to 10-s breath-hold are always close to zero. As an oral deposition function, Clark et al. chose to use the function proposed by Stahlhofen et al. and Rudolf et al., which is then numerically integrated with the size distribution derived from cascade impactor data to calculate oral deposition. Subtracting oral deposition from the inhaled dose allows calculation of the lung dose. Clark used gamma camera data from seven clinical studies, four DPI and three pMDI, to evaluate the approach. On analysis, it was seen that... 

Figure 14 A comparison of model predictions and in vivo deposition for DPIs, pMDIs, and pMDIs plus spacers as developed by Clark et al. (40), Pritchard et al. (42), and TheU (59). Data generated by Pritchard have been plotted as inhaled dose minus oral deposition, so as to make it comparable to that of Clark et al. Theil s data have been plotted directly, since a breath-holding pause was incorporated in his calculations.

Pedersen S, Steffensen G, Ohlsson SV. The influence of orally deposited budesonide on the systemic availability of budesonide after inhalation from a Turbuhaler. Br J Clin Pharmacol 1993 36 211-214. 

Assessment of airways deposition alone does not provide us with an index of the therapeutic ratio for a given drug, as the therapeutic index will change dramatically if the device is used inappropriately. For instance, acmating a pMDl but not inhaling will result in extremely high oral deposition with no therapeutic effect. 

Expiratory deposition is again eonsidered to be negligible in comparison with inspiratory deposition (163,184). Figure 9 shows deposition data predieted by the model for breathing eonditions during rest and exercise. The model assumes a eonstant respiratoiy flow rate Q, but takes into account that the colleetion efficieney decreases with inereasing tidal volume Ft. It shows that oral deposition is less dependent on flow rate than is nasal deposition, as Q is weighted by a power exponent of 0.6. Therefore, the aerodynamic particle diameter is the main... 

Oral deposition of ultrafine particles determined in physical replicates of oropharyngeal airways was slightly smaller than that measured in nasal casts (109,181,194). However, measurements performed in three healthy adults suggest that there is zero deposition for 0.1-, 0.07-, and 0.05- xm particles inhaled through the mouth under different breathing conditions (163). 

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