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.
Bazunga
M
M
University of Connecticut School of Pharmacy, Storrs, Connecticut, USA.
Tran
H T
HT
Kertland
H
H
Chow
M S
MS
Massarella
J
J
D000328:Adult; D000368:Aged; D019380:Anti-HIV Agents / Q000493:pharmacokinetics*; D005260:Female; D006207:Half-Life; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D051437:Renal Insufficiency / Q000378:metabolism*; D018894:Reverse Transcriptase Inhibitors / Q000493:pharmacokinetics*; D016047:Zalcitabine / Q000493:pharmacokinetics*
D019380:Anti-HIV Agents; D018894:Reverse Transcriptase Inhibitors; D016047:Zalcitabine