Ceftriaxone-associated neutropenia.

Abstract

TO THE EDITOR: Protein binding of quinidine has been noted to be pH-dependent with equilibrium dialysis;' however, this relationship has not been examined using ultrafiltration to separate free from protein-bound quinidine. Thus, the implication of pH dependency on protein ultracentrifugation from experiments run at unphysiological or unknown pH may be irrelevant to the in vivo conditions. The pHdependent protein binding in human serum is also found with other drugs including warfarin," lidocaine," propranolol," and disopyramide." Weused pooled serum from patients with normal liverand renal functions, and spiked the serum with either 2 or 10 mg/L of quinidine sulfate. After adjusting the pH of 10 ml of pooled serum, according to the procedure of Ponganis and Stanski,' with 0.5 M phosphoric acid (15-120I'L), the total and free quinidine concentrations were determined by fluorescence polarization immunoassayon theTDx. Freequinidineanalysiswasperformedbyultrafiltration method using an Amicon centrifree filter. The pH was determined by a Corning pH meter model 10,whichwascalibrated at 22°C. The pH dependence of serum binding of quinidine is shown in Figure I. The free fraction decreased with increasing pH. For the spiked total 10 mg/L quinidine concentration, the free fraction percentages were 25.6 ±0.69, 2\.2 ± \.05, 14.8 ±0.64, and 8.80 ± 0.38 percent REFERENCES