Tissue Changes Produced in the Nasal Mucous Membrane of Normal Mice by Prolonged Local Administration of Some Solutions Containing Sulfonamide Compounds

Abstract

PHILADELPHIANumerous reports in the literature1 reveal differences of opinion regarding human tolerance of the solutions of sulfonamide compounds used in local treatment of the nasal mucous membrane. Recently, as a result of investigations of the physiologic range of the hydrogen ion concentration of the secretions of normal nasal tissues in situ (pH fluctuating between 5.5 and 6.5) and of the changes in it observed in the course of nasal and sinus diease of man, Fabricant 2 proposed a new basis for the selection of local remedies to be administered intranasally. He stressed that markedly alkaline preparations usually exert an irritating effect on the nasal tissue, impairing the ciliary function and damaging the olfactory lining. The therapeutic problem has been to develop "a nontoxic medication, compatible with ciliary action," of the same hydrogen ion concentration as the nasal tissue and therefore "non-traumatizing to the mucous membrane." Furthermore, this author has stated that under adequate conditions of observation drug solutions with a />H range of 5.5 to 6.5 do not appear to affect markedly the nasal hydrogen ion concentration, and since the sodium salts of sulfonamide compounds are usually highly alkaline (with pn ranging between 10 and 11), their solutions are by no means free of unfavor¬ able caustic reactions.2b Fabricant concluded that, contrary to the generally accepted idea, "it is now time to acidify the nasal mucosa, not to alkalize."To prevent the irritating effect associated with high alkalinity of solutions of sulfonamide com¬ pounds, Yonkman 3 and his associates and Blackford i reeommended the use of propylene glycol as a menstruum for sulfathiazole and its sodium salt as well as for other sulfonamide compounds. They found, in particular, that 3 per cent solu¬ tions of sulfathiazole in propylene glycol were well tolerated because of the slight acidity of those solutions, with pH values within the physio¬ logic range of the nasal pH of man. Propylene glycol also seemed to have the effect of main¬ taining stable solutions.Recently the importance of animal experimen¬ tation as a basis for testing the local effect on nasal tissues of preparations containing sulfon¬ amide compounds has been emphasized.5 Such studies permit the observer to note at con¬ venient intervals the development of injury on groups of animals during and following pro¬ longed local administration of drugs. Fabricantla has summarized the experimental results ob¬ tained to date. In such experiments, Futch, Rosenvold and Stewart,5" also Gundrum,lc used rabbits, while Hunnicutt5b,c used mice. Clinical trial of new drugs recommended for nasal use