The effect of variations in urinary pH on the pharmacokinetics of diethylcarbamazine.

1 The partitioning of diethylcarbamazine (DEC) between octan-1-ol and aqueous buffer was shown to be dependent upon the pH of the buffer. 2 Buccal absorption of DEC in five subjects was shown to increase with increasing pH. 3 In view of these findings, the disposition of DEC was investigated in the same five subjects following the oral administration of 50 mg DEC citrate on two occasions. 4 The elimination half-life (T1/2) of DEC and the area under the plasma concentration v time curve (AUC) were significantly increased when an alkaline urinary pH was maintained compared with the values of these parameters obtained on a second occasion when an acidic urinary pH was maintained. Renal clearance and total urinary excretion of DEC were significantly less at alkaline urinary pH than under acidic conditions. 5 The clinical significance of these observations is discussed both with respect to dose modification under conditions of changing urinary pH and the possibility of the manipulation of urinary pH in order to produce more effective dosage regimens.