The Effects of Valproic Acid on Zidovudine Glucuronidation and Pharmacokinetics in HIV-Infected Patients.
Valproic acid
+ Zidovudine
Infections transmises par le sang+11
+ Maladies génito-urinaires
+ Maladies Génitales
Étude thérapeutique
Résumé
Preliminary studies using human liver tissue have shown that valproic acid inhibits the metabolic inactivation of zidovudine (AZT), which may prolong the plasma half-life of AZT and thus prolong the duration of the drug's effects in the body. Six asymptomatic HIV-infected patients are treated with AZT orally every 8 hours on days 1 through 4, then with a single dose on day 5 (after 8 hours of fasting), followed by pharmacokinetic sampling. On days 6 through 9, patients receive AZT orally every 8 hours in combination with valproic acid (lowest dose in the first 5 patients and a higher dose in patients 6 and 7) orally every 8 hours. On day 10, AZT and 1 of the 2 doses of valproic acid are given orally as single doses, followed by pharmacokinetic sampling. AZT is continued alone orally every 8 hours on days 11 through 14, then resumed at the patient's usual dose beginning on day 15. Per 03/09/92 amendment, dosing schedule may be modified slightly to accommodate patients with scheduling conflicts.
Protocole
Cette section fournit des détails sur le plan de l'étude, y compris la manière dont l'étude est conçue et ce qu'elle évalue.6 participants à inclure
Nombre total de participants que l'essai clinique vise à recruter.Traitement
Éligibilité
Les chercheurs recherchent des patients correspondant à une certaine description appelée critères d'éligibilité : état de santé général ou traitements antérieurs du patient.Homme
Le sexe biologique des participants éligibles à s'inscrire.De 18 à 50 ans
Tranche d'âge des participants éligibles à participer.Volontaires sains non autorisés
Indique si les individus en bonne santé et ne présentant pas la condition étudiée peuvent participer.Conditions
Pathologie
Critères
Inclusion Criteria Concurrent Medication: Allowed: Vitamins if already being taken prior to start of therapy. Patients must have: Asymptomatic HIV infection. CD4 count between 300 and 650. Prior Medication: Required: AZT at doses between 500 and 1200 mg/day for at least 6 weeks prior to enrollment. Allowed: Aspirin, Tylenol, or ibuprofen up to 48 hours prior to start of therapy. Exclusion Criteria Co-existing Condition: Patients with the following symptoms or conditions are excluded: Positive Hepatitis B surface antigen or clinical evidence of chronic active hepatitis of any type. Signs or symptoms of HIV infection including oral candidiasis, history of multidermatomal zoster, unexplained weight loss in excess of 10 percent body weight in the past 6 months, chronic diarrhea, or history of AIDS-defining opportunistic infections. Concurrent Medication: Excluded: Concomitant medications (other than AZT) for the 14 days prior to start of therapy. Patients with the following prior conditions are excluded: History of AZT intolerance including hematologic, hepatic, and/or neurologic toxicity. History of seizures. History of any antiepileptics within the past 10 years. History of abnormal bleeding or intrinsic or extrinsic coagulopathy. Signs or symptoms of HIV infection including oral candidiasis, history of multidermatomal zoster, unexplained weight loss in excess of 10 percent body weight in the past 6 months, chronic diarrhea, or history of AIDS-defining opportunistic infections. Prior Medication: Excluded: Antiepileptics within the past 10 years. Prior valproic acid. Concomitant medications (other than AZT) within 14 days of enrollment.
Centres d'étude
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