PHARMACODYNAMICS OF PULMONARY ABSORPTION IN MAN. II. THE INFLUENCE OF VARIOUS DILUENTS ON AEROSOL AND INTRATRACHEAL PENICILLIN

Publisher Website
Google Scholar
Abstract
A standard dose of 100,000 U. of crystalline K penicillin G was given to normal male volunteers. For aerosol admn. the penicillin was dissolved in 1 ml. of the diluent; the Vaponefrin nebulizer was used. For intratracheal admn. the penicillin was dissolved in 10 cc. of the diluent and injd. through a no. 12 French urethral catheter following pontocaine anesthesia of the tracheohronchial tree. Serum was assayed for penicillin activity at the end of 1/2, 1 and 2 hrs. following inhalation and at 1/2, 1 and every hr. thereafter for 6 hrs. following intratracheal admn. The serial dilution method of Rammelkamp, using the hemolytic streptococcus no. 98, was used; a level of 0.039 U./ml. of serum, by this method, inhibits most Gram-positive pathogenic organisms and was considered to be the "minimum therapeutic level." Assay of penicillin activity in the serum and recovery in the urine when admd. in various diluents was compared to results obtained following the admn. of penicillin in saline by the same routes. Both neosynephrin and epinephrine, constrictors of the bronchial mucous membrane, caused higher initial blood levels than corresponding results with saline when injd. intratracheally and levels were sustained within the therapeutic range for 5 hrs. The bronchovasoconstricting action of neosynephrine was more in evidence when aerosolized with penicillin. Triethylene glycol (100%) was too viscid for easy aero-solization and too irritating for intratracheal injn. Neither a bactericidal action of its own, enchancement of penicillin activity in the serum or a delaying action on the absorption of penicillin could be demonstrated. Chlorophyll caused more rapid absorption of penicillin but levels were not maintained within a therapeutic range for as long as with saline. A 100% soln. was irritating to the tracheobronchial tree, but a 25% soln. was well tolerated by mtratracheal instillation. Its possible value in the management of anaerobic bronchopulmonary infections is discussed. Intratracheal injn. of penicillin in lighter iodized oils and the use of human serum is also discussed.