The behavior of carbenicillin as a nonreabsorbable anion

In order to study the mechanism of hypokalemic alkalosis which occurs in some patients being treated with disodium carbenicillin, renal clearance experiments were carried out in rats and observations were made on electrical changes in isolated toad bladders. In rats maintained on a sodium-free diet, intravenous infusion of carbenicillin at 40 mg. per hour resuited in an immediate diuresis characterized by a striking increase in K and NH4 excretion, and progressive acidification of the urine. In a control group of rats, also prepared with a sodium free diet, intravenous infusion of mannitol resulted in a comparable diuresis, but no significant changes in K and NH4 excretion, and no acidification of the urine. The urinary changes in the carbenicillin-treated rats could not be accounted for by any alterations in blood electrolytes, acid-base values, or glomerular filtration rate (GFR). Isonatric, isohydric substitution of carbenicillin for chloride in the mucosal bathing media of toad bladders mounted in Ussing chambers resulted in a reversible increase in electrical potential (PD) and resistance (R) without a comparable change in short-circuit current (SCC). Substitution in the serosal medium resulted in a reversal of polarity of PD and SCC in 4 of 9 experiments, a finding best explained by more rapid movement of chloride from M leads to S than carbenicillin movement from S leads to M (a chloride diffusion potential). The observations in both the rat and toad bladder experiments are consistent with the view that carbenicillin behaves as a nonreabsorbable anion. Hypokalemic alkalosis in patients receiving this drug can thus be attributed to increased electrical negativity of the distal nephron with subsequent enhancement of K and H secretion.