TY - JOUR
T1 - Multiple-dose pharmacokinetics of delavirdine mesylate and didanosine in HIV-infected patients
AU - Morse, Gene D.
AU - Cohn, Susan E.
AU - Shelton, Mark J.
AU - Greisberger, Carol
AU - Cox, Steven R.
AU - Della-Coletta, Andrew A.
AU - Freimuth, William W.
AU - Reichman, Richard C.
N1 - Funding Information:
This work was supported in part by the University of Rochester General Clinical Research Center NIH-DRR-GCRC Grant 5M01-RR-00044 and by a grant from Agouron Inc. (a Pfizer company). The assistance of the nursing staff of the Clinical Research Center is appreciated.
PY - 2003
Y1 - 2003
N2 - 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 (Cmax) [22.4 ± 11 vs 35.5 ± 17μM; p = 0.045] was noted when delavirdine and didanosine were taken together. However, no significant difference was noted for delavirdine AUC (114 ± 56 μM•h compared with 153 ± 79 μM•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.
AB - 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 (Cmax) [22.4 ± 11 vs 35.5 ± 17μM; p = 0.045] was noted when delavirdine and didanosine were taken together. However, no significant difference was noted for delavirdine AUC (114 ± 56 μM•h compared with 153 ± 79 μM•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.
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U2 - 10.2165/00044011-200323050-00002
DO - 10.2165/00044011-200323050-00002
M3 - Article
C2 - 17535044
AN - SCOPUS:0013056392
SN - 1173-2563
VL - 23
SP - 323
EP - 328
JO - Clinical Drug Investigation
JF - Clinical Drug Investigation
IS - 5
ER -