PT  - JOURNAL ARTICLE
AU  - David M. Travis
AU  - Christine Wiley
AU  - Thomas H. Maren
TI  - RESPIRATION DURING CHRONIC INHIBITION OF RENAL CARBONIC ANHYDRASE: FURTHER OBSERVATIONS ON PHARMACOLOGY OF 2-BENZENESULFONAMIDO-1,3,4-THIADIAZOLE-5-SULFONAMIDE (CL 11,366), ACETAZOLAMIDE AND METHAZOLAMIDE
DP  - 1966 Mar 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 464--481
VI  - 151
IP  - 3
4099  - http://jpet.aspetjournals.org/content/151/3/464.short
4100  - http://jpet.aspetjournals.org/content/151/3/464.full
SO  - J Pharmacol Exp Ther1966 Mar 01; 151
AB  - Selective renal carbonic anhydrase inhibition with full renal HCO3- response may be obtained without respiratory effect of erythrocytic enzyme inhibition during chronic administration of 2-benzenesulfonamido-1,3,4-thiadiazole -5-sulfonamide (CL 11,366) in unanesthetized dogs by appropriate choice of dose and interval. As little as 0.5 mg/kg i.m. gives maximal rates of renal HCO3- loss, and administration every 4 hr approaches maximally sustained plasma HCO3- depletion. As much as 10 mg/kg p.o. every 12 hr fails to bring about respiratory changes characteristic of erythrocytic inhibition. Studies of distribution of CL 11,366 show it to be concentrated in kidney and lung, where it is apparently secreted, and to be low in muscle and brain, from which it is largely excluded because of high plasma binding and poor diffusibility. Exclusion of physiologically effective concentration from erythrocytes is possible because the composite of chemical and pharmacologic factors keep free drug in the red cells at a lower level than the unbound plasma inhibitor concentration, which is small at maximum renal doses. The Williams & Wilkins Comapny