Lung pH and pulmonary absorption of nonvolatile drugs in the rat.

The effect of pH on pulmonary absorption of nonvolatile drugs was investigated in the rat. Krebs-Ringer phosphate solutions (pH 6.2 and 7.4), Krebs-Ringer pyrophosphate solution (pH 8.4), or an unbuffered salt solution containing a drug were administered through tight-fitting tracheal cannulas to anesthetized animals. After 3 min, the lungs were removed and assayed for the amount of drug that remained. Weak acids and a weak base were absorbed most rapidly at pH values at which the drugs were least ionized. For example, with the base procainamide, 36% of the dose was absorbed at pH 6.2 and 76% at pH 8.4. With the acid sulfisoxazole, 71% was absorbed at pH 6.2 and 55% at pH 8.4. Similarly, with p-aminosalicylic acid, 77% was absorbed at pH 6.2 and 40% at pH 8.4. In contrast to these results, compounds such as urea and amitrole, which remain completely nonionized over the pH range studied, showed no change in absorption rate when the pH was varied. The two weak acids and the weak base were absorbed from an unbuffered solution as though the pH at the site of drug absorption was between 6.2 and 7.4. The absorption rate for each weak electrolyte from unbuffered solution, when compared graphically with the respective absorption rates from buffered solutions, indicated that the pH at the site of drug absorption is about 6.6.