THE EFFECTS OF RENAL IMPAIRMENT ON THE PHARMACOKINETICS OF ZALCITABINE

The pharmacokinetics of zalcitabine (ddC) were studied in three groups of subjects with varying degrees of renal function: group I (n = 5), creatinine clearance (Cl-cr 0-10 mL/min; group II (n = 10), Cl-cr 11-5 0 mL/min; and group III (n = 8), Cl-cr > 50 mL/min. Each patient recei ved a single 0.75-mg oral dose of zalcitabine, and multiple blood and urine samples were collected over a 10-hour period after administratio n. Plasma and urine concentrations of zalcitabine were measured by hig h-performance liquid chromatography. No statistically significant diff erences were observed between the three groups in maximum concentratio n (C-max), time to C-max (t(max)), or volume of distribution (V/F). Al so, elimination half-life (t(1/2)), area under the concentration-time curve (AUC(0.10)), total body clearance (Cl/F), elimination rate const ant (Ke), and renal clearance (Cl-r did not differ significantly betwe en the two groups with renal impairment (groups I and II). However, th ere was a significant difference in these parameters between groups wi th renal impairment (I and II) and group III. A linear correlation was observed between creatinine clearance (Cl-cr) and Cl-r, Ke, and Cl/F in all subjects. Clearance of zalcitabine is decreased after a single oral dose in patients with renal impairment. Dosage adjustment may be warranted in such patients, especially in those with severe renal impa irment.