Effects of standard breakfast on pharmacokinetics of oral zidovudine in patients with AIDS

Abstract

The influence of a standard breakfast on the single-dose pharmacokinetics of zidovudine (AZT) after oral administration of 100 and 250 mg of AZT was studied in 27 subjects with advanced human immunodeficiency virus infection (Centers for Disease Control stage IV). Concentrations of AZT and the 5'-glucuronide metabolite (GAZT) [B]). Recoveries (AZT and GAZT) in urine varied with both dosages, reflecting more a problem of accounting for the metabolite GAZT in urine than a relevant difference (100 mg, 115% [F] and 76.5% [B]; 250 mg, 71% [F] and 99.4% [B]). Our data suggest that absorption of AZT in human immunodeficiency virus-infected subjects is extremely variable, with a high degree of interindividual differences. Furthermore, breakfast had a marked influence on the absorption of AZT, suggesting that the drug should be taken in a fasting state.

Didanosine, Lamivudine, and Efavirenz versus Zidovudine, Lamivudine, and Efavirenz for the Initial Treatment of HIV Type 1 Infection: Final Analysis (48 Weeks) of a Prospective, Randomized, Noninferiority Clinical Trial, GESIDA 3903

“…It should be taken into account, however, that the absorption of other NRTIs is also reduced when they are taken with food. For example, food reduces drug exposure by 20% for zidovudine [19,20] and by 27% for zalcitabine [21], but there are no data to support that taking these drugs with food may cause therapeutic failure. The results of our trial show that the clinical significance of such moderate reductions in ddI exposure with food, especially as part of a HAART regimen, is null.…”

“…Randomization was centralized and stratified by entry HIV-1 RNA level of !100,000 copies/mL, 100,000 copies/mL, or (7) 6 (3) 19 (5) .096 C 37 (20) 38 (21) 75 (21) .425 B and C 5 (3) 1 (1) 6 (2) .120 HIV-1 RNA level Median log 10 copies/mL (IQR) 5.0 (4.5-5.4) 5.0 (4.5-5.5) 5.0 (4.5-5.5) .817 у100,000 cop/mL 102 (55) and abnormal laboratory results. The severity of adverse events and laboratory abnormalities were graded according to the World Health Organization Toxicity Grading Scale [7].…”

Interactions of Antineoplastic Chemotherapy with Zidovudine Pharmacokinetics in Patients with HIV-Related Neoplasms

“…The antineoplastic drugs could determine some effects on the gastrointestinal mucosa by affecting gastric motility, which could interfere with the kinetics of ZDV absorption, as demonstrated for other drugs [20,27]. It must be considered that Ruhnke et al [28] reported a decrease in ZDV peak after food intake as a consequence of inhibition of gastric emptying. Conversely, we do not think that perturbations in ZDV kinetic absorption could be due to the antiemetics we used since they do not generally interfere with gastric motility.…”

Zidovudine

“…After oral zidovudine 2 or 5mg every 8 hours or 5 or 10mg every 4 hours the C max range was 0.53 Zidovudine: A Review 523 to 2.53 mg/L and generally occurred 0.5 hours after administration (t max ). [48,49] Zidovudine is highly lipophilic and is widely distributed in body fluids and tissues, with a mean steady-state apparent volume of distribution (Vd) in patients with AIDS of 1.4 L/kg. Concomitant food consumption, especially high fat meals, [48] tends to delay t max and reduce the C max of zidovudine, although systemic exposure (measured as the AUC) is not appreciably affected in patients with HIV infection.…”