Db. May et al., EFFECT OF SIMULTANEOUS DIDANOSINE ADMINISTRATION ON ITRACONAZOLE ABSORPTION IN HEALTHY-VOLUNTEERS, Pharmacotherapy, 14(5), 1994, pp. 509-513
Study Objective. To investigate the effect of simultaneously administe
red didanosine (ddI) on the absorption of a single dose of itraconazol
e. Design. Randomized, crossover, unblinded single-dose pharmacokineti
c study in healthy volunteers. Comparisons of itraconazole alone and i
traconazole with simultaneous ddI were performed on days 1 and 15. Set
ting. A university medical center. Patients. Seven healthy men and wom
en. Six subjects (86%) completed the study; one was removed due to the
development of a rash. Interventions. Volunteers received a single 20
0-mg oral dose of itraconazole or itraconazole with concomitant oral d
dI 300 mg (two 150-mg tablets) dispersed in 240 ml water. Each regimen
was separated by a 2-week washout period. Serum samples were obtained
frequently for 12 hours after the dose. Measurements and Main Results
. Concentrations of itraconazole were determined using a microbiologic
assay. Individual concentrations in serum versus time data were evalu
ated by linear regression analysis. Peak serum concentration and time
to peak were determined by visual inspection of each individual's seru
m concentration-time curve. A mean +/- SD peak serum itraconazole conc
entration of 0.90 +/- 0.30 mu g/ml was observed at 3.0 +/- 0.7 hours w
hen itraconazole was administered alone, compared with undetectable le
vels in all patients during therapy with ddI. Conclusions. Simultaneou
s oral administration of ddI significantly decreases absorption of itr
aconazole. These drugs should not be administered concurrently