(n = 21) 1.9 ± 0.7

(n = 18) 1.5 ± 0.7

(n = 21)
aData presented as mean ± standard deviation except where noted.
bCSF ratio determined at steady-state on constant intravenous infusion.
Pregnancy: Zidovudine pharmacokinetics have been studied in a Phase 1 study of 8 women during the last trimester of pregnancy. As pregnancy progressed, there was no evidence of drug accumulation. Zidovudine pharmacokinetics were similar to those of nonpregnant adults. Consistent with passive transmission of the drug across the placenta, zidovudine concentrations in neonatal plasma at birth were essentially equal to those in maternal plasma at delivery. Although data are limited, methadone maintenance therapy in 5 pregnant women did not appear to alter zidovudine pharmacokinetics. However, in another patient population, a potential for interaction has been identified (see PRECAUTIONS).

Nursing Mothers: The Centers for Disease Control and Prevention recommend that HIV-infected mothers not breastfeed their infants to avoid risking postnatal transmission of HIV. After administration of a single dose of 200 mg zidovudine to 13 HIV-infected women, the mean concentration of zidovudine was similar in human milk and serum (see PRECAUTIONS: Nursing Mothers).

Geriatric Patients: Zidovudine pharmacokinetics have not been studied in patients over 65 years of age.

Gender: A pharmacokinetic study in healthy male (n = 12) and female (n = 12) subjects showed no differences in zidovudine exposure (AUC) when a single dose of zidovudine was administered as the 300-mg RETROVIR Tablet.
Drug Interactions:
See Table 4 and PRECAUTIONS: Drug Interactions.

Zidovudine Plus Lamivudine: No clinically significant alterations in lamivudine or zidovudine pharmacokinetics were observed in 12 asymptomatic HIV-infected adult patients given a single oral dose of zidovudine (200 mg) in combination with multiple oral doses of lamivudine (300 mg every 12 hours).

Table 4. Effect of Coadministered Drugs on Zidovudine AUC a Note: ROUTINE DOSE MODIFICATION OF ZIDOVUDINE IS NOT WARRANTED WITH COADMINISTRATION OF THE FOLLOWING DRUGS.  Coadministered Drug and Dose Zidovudine Oral Dose n Zidovudine Concentrations Concentration of Coadministered Drug
AUC Variability
Atovaquone

750 mg q 12 hr with food 200 mg q 8 hr 14 ↑AUC 31% Range

23% to 78%b ↔
Fluconazole

400 mg daily 200 mg q 8 hr 12 ↑AUC 74% 95% CI:

54% to 98% Not Reported
Methadone

30 to 90 mg daily 200 mg q 4 hr 9 ↑AUC 43% Range

16% to 64%b ↔
Nelfinavir

750 mg q 8 hr x 7 to 10 days single 200 mg 11 ↓AUC 35% Range

28% to 41% ↔
Probenecid

500 mg q 6 hr x 2 days 2 mg/kg q 8 hr x 3 days 3 ↑AUC 106% Range

100% to 170%b Not Assessed
Rifampin

600 mg daily x 14 days 200 mg q 8 hr x 14 days 8 ↓AUC 47% 90% CI:

41% to 53% Not Assessed
Ritonavir

300 mg q 6 hr x 4 days 200 mg q 8 hr x 4 days 9 ↓AUC 25% 95% CI:

15% to 34% ↔
Valproic acid

250 mg or 500 mg q 8 hr x 4 days 100 mg q 8 hr x 4 days 6 ↑AUC 80% Range

64% to 130%b Not Assessed
↑ = Increase; ↓ = Decrease;↔ = no significant change; AUC = area under the concentration versus time curve; CI = confidence interval.
aThis table is not all inclusive.
bEstimated range of percent difference.
Ribavirin: In vitro data indicate ribavirin reduces phosphorylation of lamivudine, stavudine