title: In silico study supports the efficacy of a reduced dose regimen for stavudine.
abstract: Stavudine (d4T) is used extensively as part of HAART in resource poor settings, despite its toxicities. The revised WHO guidelines specify replacement of d4T with less toxic but more expensive drugs when feasible, and that d4T doses be standardized to 30 mg twice daily (bid) (irrespective of body-weight), from the approved 40 mg bid in adults (body-weight ≥60 kg). Therefore, an in silico population pharmacokinetic and biochemical model was utilized to compare relative efficacies of the two doses in humans. Assessment of predicted quartile ranges of simulated concentrations of the triphosphate of d4T suggested sufficient trough concentrations to inhibit wild type HIV-1 reverse transcriptase at the reduced dose, lending support to the revised WHO recommendations.
authors.affiliation: Center for AIDS Research, Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine, Atlanta, GA 30322, USA.
authors.forename: Selwyn J
authors.initials: SJ
authors.lastname: Hurwitz
authors.forename: Raymond F
authors.initials: RF
authors.lastname: Schinazi
mesh_terms: D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000009:adverse effects; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology*; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D015233:Models, Statistical; D018119:Stavudine / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: D019380:Anti-HIV Agents; D018119:Stavudine