The pharmacokinetics and tolerance of oral zidovudine were eva luated in a multiple-dose study in patients undergoing hemodialysis (n = 5) or peritoneal dialysis (n = 6) receiving escalating doses up to 200 mg 5 times daily for 8 weeks. Daily doses of 500 mg or less were well tolerated despite significantly elevated GZDV plasma concentrations. Apparent zidovudine oral clearance was approximately 50% of that reported in patients with normal renal function. Hemodialysis and peritoneal dialysis appeared to have a negligible effect on the removal of zidovudine, whereas GZDV elimination was enhanced. A dosage adjustment is recommended for patients undergoing hemodialysis or peritoneal dialysis (see DOSAGE AND ADMINISTRATION: Dose Adjustment).

Adults With Impaired Hepatic Function: Data describing the effect of hepatic impairment on the pharmacokinetics of zidovudine are limited. However, because zidovudine is eliminated primarily by hepatic metabolism, it is expected that zidovudine clearance would be decreased and plasma concentrations would be increased following administration of the recommended adult doses to patients with hepatic impairment (see DOSAGE AND ADMINISTRATION: Dose Adjustment).

Pediatrics: Zidovudine pharmacokinetics have been eva luated in HIV-infected pediatric patients (Table 3).

Patients From 3 Months to 12 Years of Age: Overall, zidovudine pharmacokinetics in pediatric patients >3 months of age are similar to those in adult patients. Proportional increases in plasma zidovudine concentrations were observed following administration of oral solution from 90 to 240 mg/m2 every 6 hours. Oral bioavailability, terminal half-life, and oral clearance were comparable to adult values. As in adult patients, the major route of elimination was by metabolism to GZDV. After intravenous dosing, about 29% of the dose was excreted in the urine unchanged and about 45% of the dose was excreted as GZDV (see DOSAGE AND ADMINISTRATION: Pediatrics).

Patients Younger Than 3 Months of Age: Zidovudine pharmacokinetics have been eva luated in pediatric patients from birth to 3 months of life. Zidovudine elimination was determined immediately following birth in 8 neonates who were exposed to zidovudine in utero. The half-life was 13.0 ± 5.8 hours. In neonates ≤14 days old, bioavailability was greater, total body clearance was slower, and half-life was longer than in pediatric patients >14 days old. For dose recommendations for neonates, see DOSAGE AND ADMINISTRATION: Neonatal Dosing.
Table 3. Zidovudine Pharmacokinetic Parameters in Pediatric Patients a  Parameter Birth to 14 Days of Age 14 Days to 3 Months of Age 3 Months to 12 Years of Age
Oral bioavailability (%) 89 ± 19

(n = 15) 61 ± 19

(n = 17) 65 ± 24

(n = 18)
CSF:plasma ratio no data no data 0.26 ± 0.17b

(n = 28)
CL (L/hr/kg) 0.65 ± 0.29

(n = 18) 1.14 ± 0.24

(n = 16) 1.85 ± 0.47

(n = 20)
Elimination half-