DRUG-DELIVERY VIA THE RESPIRATORY-TRACT

Inhalation offers an enormous absorptive surface area for rapid drug a bsorption and substantial absorption of polypeptides. Due to slow clea rance from the lower lung, even compounds with very small absorption r ates can be absorbed in significant quantities over 10-12h periods. Ae rosol dosimetry problems can also be minimized when lung-normal patien ts are considered. In the near future, optimal formulations will be co mbined with modified aerosol delivery devices to achieve reproducible dosing. These will be used as alternatives to parenteral delivery for drug doses of the order of milligrams or less. Research on the molecul ar structural dependence of lung disposition is in its infancy. Absorp tion kinetics for small molecules are known to depend on lipophilicity and molecular size. For macromolecules however, electronic charge and site of deposition may be additional determinants of bioavailability. Carrier-mediated absorption processes may also be important. The pulm onary absorption of a number of molecules is reviewed with special emp hasis on new and promising products of biotechnology like human insuli n and human growth hormone. Delivery improvements in the future should ensure, ideally, that nondenatured, monomeric pure compounds are deli vered reproducibly and predominantly to the lung itself, so that these compounds may elicit reproducible systemic effects following absorpti on.