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 (Clcr) 0-10 mL/min; group II (n = 10), Clcr 11-50 mL/min; and group III (n = 8), Clcr > 50 mL/min. Each patient received a single 0.75-mg oral dose of zalcitabine, and multiple blood and urine samples were collected over a 10-hour period after administration. Plasma and urine concentrations of zalcitabine were measured by high-performance liquid chromatography. No statistically significant differences were observed between the three groups in maximum concentration (Cmax), time to Cmax (tmax), or volume of distribution (V/F). Also, elimination half-life (t1/2), area under the concentration-time curve (AUC0-10), total body clearance (Cl/F), elimination rate constant (Ke), and renal clearance (Clr) did not differ significantly between the two groups with renal impairment (groups I and II). However, there was a significant difference in these parameters between groups with renal impairment (I and II) and group III. A linear correlation was observed between creatinine clearance (Clcr) and Clr, 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 impairment.
CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter    What's this?