BACKGROUND:Delavirdine is a non-nucleoside reverse transcriptase inhibitor with pH-dependent absorption characteristics that has received accelerated approval for the treatment of patients with HIV-1 infection. In a prior single-dose study concurrent administration of delavirdine mesylate and didanosine (buffered formulation) resulted in up to a 31% decrease in the area under the plasma delavirdine concentration versus time curve (AUC) compared with when both drugs were taken separately. OBJECTIVE: To evaluate the interaction of these two agents at steady state. STUDY DESIGN AND PATIENTS: A total of 11 HIV-infected subjects who were previously stabilised ondidanosine were enrolled into a randomised, open-labelled crossover study. Nine subjects continued to receive their prescribed dose and schedule of didanosine, with each dose of didanosine taken either together with or 1 hour after delavirdine mesylate (400mg every 8 hours). Pharmacokinetic studies at baseline, day 14 and day 28 were conducted and the plasma concentrations of delavirdine and didanosine were determined. RESULTS: A lower delavirdine maximum plasma concentration (C(max)) [22.4 +/- 11 vs 35.5 +/- 17muM; p = 0.045] was noted when delavirdine and didanosine were taken together. However, no significant difference was noted for delavirdine AUC (114 +/- 56 muM.h compared with 153 +/- 79 muM.h [p = 0.181]). In addition, no differences were noted for didanosine pharmacokinetic parameters between treatments. CONCLUSION: These data indicate that patients receiving didanosine and delavirdine as part of a combination regimen during long-term therapy can be instructed to take them together in an attempt to enhance adherence to treatment with both antiretroviral agents.
RCT Entities:
BACKGROUND:Delavirdine is a non-nucleoside reverse transcriptase inhibitor with pH-dependent absorption characteristics that has received accelerated approval for the treatment of patients with HIV-1 infection. In a prior single-dose study concurrent administration of delavirdine mesylate and didanosine (buffered formulation) resulted in up to a 31% decrease in the area under the plasma delavirdine concentration versus time curve (AUC) compared with when both drugs were taken separately. OBJECTIVE: To evaluate the interaction of these two agents at steady state. STUDY DESIGN AND PATIENTS: A total of 11 HIV-infected subjects who were previously stabilised on didanosine were enrolled into a randomised, open-labelled crossover study. Nine subjects continued to receive their prescribed dose and schedule of didanosine, with each dose of didanosine taken either together with or 1 hour after delavirdine mesylate (400mg every 8 hours). Pharmacokinetic studies at baseline, day 14 and day 28 were conducted and the plasma concentrations of delavirdine and didanosine were determined. RESULTS: A lower delavirdine maximum plasma concentration (C(max)) [22.4 +/- 11 vs 35.5 +/- 17muM; p = 0.045] was noted when delavirdine and didanosine were taken together. However, no significant difference was noted for delavirdine AUC (114 +/- 56 muM.h compared with 153 +/- 79 muM.h [p = 0.181]). In addition, no differences were noted for didanosine pharmacokinetic parameters between treatments. CONCLUSION: These data indicate that patients receiving didanosine and delavirdine as part of a combination regimen during long-term therapy can be instructed to take them together in an attempt to enhance adherence to treatment with both antiretroviral agents.
Authors: C V Fletcher; E P Acosta; H Cheng; R Haubrich; M Fischl; R Raasch; C Mills; X J Hu; D Katzenstein; R P Remmel; R M Gulick Journal: AIDS Date: 2000-11-10 Impact factor: 4.177
Authors: G H Friedland; R Pollard; B Griffith; M Hughes; G Morse; R Bassett; W Freimuth; L Demeter; E Connick; T Nevin; M Hirsch; M Fischl Journal: J Acquir Immune Defic Syndr Date: 1999-08-01 Impact factor: 3.731
Authors: M F Para; P Meehan; J Holden-Wiltse; M Fischl; G Morse; R Shafer; L M Demeter; K Wood; T Nevin; N Virani-Ketter; W W Freimuth Journal: Antimicrob Agents Chemother Date: 1999-06 Impact factor: 5.191
Authors: T J Dueweke; S M Poppe; D L Romero; S M Swaney; A G So; K M Downey; I W Althaus; F Reusser; M Busso; L Resnick Journal: Antimicrob Agents Chemother Date: 1993-05 Impact factor: 5.191
Authors: Gene D Morse; Margaret A Fischl; Mark J Shelton; Steve R Cox; Leslie Thompson; Andrew A Della-Coletta; William W Freimuth Journal: Clin Drug Investig Date: 2003 Impact factor: 2.859