Effects of pH on the accumulation of sulfonamides by fish.

The pH of water affects the accumulation of weak electrolytes by fish in the water. However, the relationships among water pH, weak electrolyte pKa and the rate and extent of accumulation of the weak electrolyte are poorly characterized. To better define these relationships, goldfish were immersed for varying periods of time in solutions of sulfonamides that were buffered at pH values from 5.4 to 9.4. Sulfapyridine, sulfisomidine, and sulfadimethoxine were chosen for investigation, because their pKa's, 8.4, 7.4, and 5.9, respectively, bracketed the pH of fish body fluids. Each fish carcass was assayed for the amount of sulfonamide that had accumulated. Several pharmacokinetic models were used to analyze the data. The model that best described the accumulation of the sulfonamides represented the fish as a single compartment having an apparent volume of distribution (V) and clearance constants for absorption of both the nonionized (kHA) and ionized (kA) forms. Values of V were between 5 and 60% of the body weight of the fish. Values for kA were all approximately 0.2 microliters/min/g fish, while values of kHA were 3-100 times larger than the corresponding kA values. The kHA values correlated with the isoamyl acetate/water partition coefficients of the nonionized forms. The extent of accumulation of the sulfonamides showed two pH-independent regions, with the low pH having the greater accumulation. The pH midway between the two regions was equal to the pKa of the sulfonamide. The accumulation half-lives were 1.5-4.5 hr and independent of the pH of the water.