89016
document
Single-dose pharmacokinetics of delavirdine mesylate and didanosine in patients with human immunodeficiency virus infection . Delavirdine is a nonnucleoside reverse transcriptase inhibitor with in vitro activity against human immunodeficiency virus type 1 ( HIV-1 ) that is currently being evaluated in combination regimens with various nucleoside analogs , including didanosine . Due to the pH-dependent solubility of delavirdine , the buffering agents in didanosine formulations may reduce delavirdine absorption . To evaluate the potential interaction between these agents , 12 HIV-infected patients ( mean [ +/- standard deviation ] CD4+ cell count , 304 +/- 213/mm3 ) were enrolled in a three-way crossover single-dose study . Didanosine ( 125 to 200 mg given as buffered tablets ) and delavirdine mesylate ( 400 mg ) pharmacokinetics were evaluated when each drug was given alone ( treatments A and B , respectively ) , when the two drugs were given concurrently ( treatment C ) , and when didanosine was given 1 h after delavirdine ( treatment D ) . Delavirdine exposure was reduced by concurrent administration of didanosine . The maximum drug concentration in serum ( Cmax ) was reduced from 7.22 +/- 4.0 to 3.51 +/- 1.9 microM , and the area under the concentration-time curve from 0 h to infinity ( AUC0 -- > infinity ) was reduced from 22.5 +/- 14 to 14 +/- 5.7 microM.h . The extent of N-dealkylation , as indicated by the ratio of the N-dealkylated delavirdine AUC0 -- > infinity to the delavirdine AUC0 -- > infinity , was unchanged across study treatments ( P = 0.708 ) . Reductions in didanosine exposure were observed during concurrent administration with delavirdine with a Cmax reduction from 4.65 +/- 2.0 to 3.22 +/- 0.59 microM and an AUC0 -- > infinity reduction from 7.93 +/- 3.9 to 6.54 +/- 2.3 microM.h . Thus , concurrent administration of delavirdine and didanosine may reduce the AUC0 -- > infinity of both drugs , although the clinical significance of this reduction is unknown . Administration of delavirdine 1 h before didanosine avoided the interaction . Due to the single-dose nature of this study , these findings require further evaluation at steady state .
89017
Intervention_Pharmacological
delavirdine mesylate
89018
Intervention_Pharmacological
didanosine
89019
Intervention_Pharmacological
Didanosine
89020
Intervention_Pharmacological
delavirdine mesylate
89021
Intervention_Pharmacological
didanosine
89022
Intervention_Pharmacological
delavirdine
89023
Intervention_Pharmacological
Delavirdine
89024
Intervention_Pharmacological
didanosine
89025
Intervention_Pharmacological
delavirdine
89026
Intervention_Pharmacological
didanosine
89027
Outcome_Other
Delavirdine exposure
89028
Outcome_Other
maximum drug concentration in serum ( Cmax )
89029
Outcome_Other
area under the concentration-time curve
89030
Outcome_Other
extent of N-dealkylation
89031
Outcome_Other
ratio of the N-dealkylated delavirdine AUC0 -- > infinity
89032
Outcome_Other
delavirdine AUC0 -- > infinity
89033
Outcome_Other
didanosine exposure
89034
Outcome_Other
Cmax
89035
Outcome_Other
AUC0 -- > infinity
89036
Participant_Condition
human immunodeficiency virus infection
89037
Participant_Condition
human immunodeficiency virus type 1 ( HIV-1 )
89038
Participant_Condition
12