Lack of Pharmacokinetic Interaction between Amdoxovir and Reduced- and Standard-Dose Zidovudine in HIV-1-Infected Individuals
| Autor: | Phillip M. Tharnish, Raymond F. Schinazi, Emilie Fromentin, Selwyn J. Hurwitz, Ghazia Asif |
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| Rok vydání: | 2010 |
| Předmět: |
Adult
Male Anti-HIV Agents HIV Infections Urine Pharmacology Biology Placebo Drug Administration Schedule Young Adult chemistry.chemical_compound Zidovudine Pharmacokinetics immune system diseases medicine Humans Drug Interactions Pharmacology (medical) Active metabolite Reverse-transcriptase inhibitor virus diseases Dioxolanes Purine Nucleosides Middle Aged Treatment Outcome Infectious Diseases chemistry Toxicity HIV-1 Reverse Transcriptase Inhibitors Female Amdoxovir medicine.drug |
| Zdroj: | Antimicrobial Agents and Chemotherapy. 54:1248-1255 |
| ISSN: | 1098-6596 0066-4804 |
| DOI: | 10.1128/aac.01209-09 |
| Popis: | Amdoxovir (AMDX) inhibits HIV-1 containing the M184V/I mutation and is rapidly absorbed and deaminated to its active metabolite, β-d-dioxolane guanosine (DXG). DXG is synergistic with zidovudine (ZDV) in HIV-1-infected primary human lymphocytes. A recentin silicopharmacokinetic (PK)/enzyme kinetic study suggested that ZDV at 200 mg twice a day (b.i.d.) may reduce toxicity without compromising efficacy relative to the standard 300-mg b.i.d. dose. Therefore, an intense PK clinical study was conducted using AMDX/placebo, with or without ZDV, in 24 subjects randomized to receive oral AMDX at 500 mg b.i.d., AMDX at 500 mg plus ZDV at 200 or 300 mg b.i.d., or ZDV at 200 or 300 mg b.i.d. for 10 days. Full plasma PK profiles were collected on days 1 and 10, and complete urine sampling was performed on day 9. Plasma and urine concentrations of AMDX, DXG, ZDV, and ZDV-5′-O-glucuronide (GZDV) were measured using a validated liquid chromatography-tandem mass spectrometry method. Data were analyzed using noncompartmental methods, and multiple comparisons were performed on the log-transformed parameters, at steady state. Coadministration of AMDX with ZDV did not significantly change either of the plasma PK parameters or percent recovery in the urine of AMDX, DXG, or ZDV/GZDV. Larger studies with AMDX/ZDV, with a longer duration, are warranted. |
| Databáze: | OpenAIRE |
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