Pulmonary absorption rate constants

Fig. 2 Apparent pulmonary absorption rate constants as a function of molecular weight calculated from data in (From Dr. Glyn Taylor, University of Wales, Cardiff, UK, and Dr. Stephen Farr, Aradigm Corporation, Hayward, CA.)...

The lack of activity after oral administration for most peptides and proteins resulted in the past besides parenteral application into the utilization of nonoral administration pathways, for example, nasal, buccal, rectal, vaginal, percutaneous, ocular, or pulmonary drug delivery [27]. Drug delivery via these administration routes, however, is also frequently accompanied by presystemic degradation processes. Bioavailability of numerous peptides and proteins is, for example, markedly reduced after subcutaneous or intramuscular administration compared to their intravenous administration. The pharma-cokinetically derived apparent absorption rate constant is thus the combination of absorption into the systemic circulation and presystemic degradation at the absorption... 

Fig. 17. Biological model recommended for describing the uptake and retention of cerium by humans after inhalation or ingestion. Numbers in parentheses give the fractions of the material in the originating compartments which are cleared to the indicated sites of deposition. Clearance from the pulmonary region results from competition between mechanical clearances to the lymph nodes and gastrointestinal tract and absorption of soluble material into the systemic circulation. The fractions included in parentheses by the pulmonary compartment indicate the distribution of material subject to the two clearance rates however, these amounts will not be cleared in this manner if the material is previously absorbed into blood. Transfer rate constants or functions, S(t), are given in fractions per unit time. Dashed lines indicate clearance pathways which exist but occur at such slow rates as to be considered insignificant compared to radioactive decay of the cerium isotopes.

Clearance to pulmonary lymph nodes will occur at a fractional rate of 0.0001 per day. Dissolution of the deposited particles and absorption of cerium into the systemic circulation will occur at rates that are between the extremes represented by CeCh in CsCl particles and Ce oxide or Ce in fused aluminosilicate particles as given by the functions included in Figure 9. These rates should not be expected to be constant over the entire clearance period and will depend upon the overall composition of the bulk aerosol particles, which indude particle size, amount of stable lanthanide present, acidity, and the solubility of other components of the particles. The accuracy of predicting respiratory tract clearance and internal organ uptake of radiocerium will depend heavily upon adequate determination of the particle solubility characteristics. 

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