Pharmacokinetic interaction study of indinavir/ritonavir and the enteric-coated capsule formulation of didanosine in healthy volunteers.
Didanosine enteric-coated should be taken on an empty stomach, but the once-daily combination of indinavir/ritonavir can be taken with food. Because these drugs are frequently included in 1 regimen, the food effects on the pharmacokinetics were evaluated. This was a randomized, 4-way crossover study of single doses of didanosine enteric-coated 400 mg and indinavir/ritonavir 1200/400 mg in 8 healthy subjects. The following regimens were given: didanosine enteric-coated 2 hours after breakfast (reference regimen A), indinavir/ritonavir with breakfast (reference regimen B), didanosine enteric-coated + indinavir/ritonavir 2 hours after breakfast (test regimen C), and didanosine enteric-coated + indinavir/ritonavir with breakfast (test regimen D). Breakfast was 550 kcal, 28% fat. Blood samples were drawn before and up to 24 hours after ingestion. Statistical comparisons of test regimens C and D with reference regimens A and B were made using the equivalence approach for indinavir and didanosine area under the curve and C(max) (0.80-1.25). Eight subjects (5 men, 3 women) were enrolled and completed the study. Indinavir area under the curves were bioequivalent in test regimens C and D compared to reference regimen B. A 14% increased C(max) was observed in test regimen C. Didanosine area under the curve in test regimen D was 4% lower and suggestive of bioequivalence compared to reference regimen A. However, test regimen C didanosine area under the curve was 23% lower and bioinequivalent compared to reference regimen A. Didanosine C(max) decreased 42% and 46% in test regimens C and D, respectively, in comparison to reference regimen A. In this study, dosing didanosine enteric-coated 400 mg once daily + indinavir/ritonavir 1200/400 mg once daily with breakfast indicated no decrease in the amount of absorption for either didanosine and indinavir and that this regimen could be administered with food.
la Porte
C
C
Department of Clinical Pharmacy, University Medical Centre Nijmegen, PO Box 9101, 533 KF, 6500 HB, Nijmegen, the Netherlands.
Verweij-van Wissen
C
C
van Ewijk
N
N
Aarnoutse
R
R
Koopmans
P
P
Reiss
P
P
Stek
M
M
Hekster
Y
Y
Burger
D
D
D000284:Administration, Oral; D000328:Adult; D019540:Area Under Curve; D002214:Capsules; D018592:Cross-Over Studies; D003692:Delayed-Action Preparations; D016049:Didanosine / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics*; D004334:Drug Administration Schedule; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D005260:Female; D018565:Food-Drug Interactions; D006207:Half-Life; D064368:Healthy Volunteers; D006801:Humans; D019469:Indinavir / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology; D008297:Male; D015203:Reproducibility of Results; D019438:Ritonavir / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology; D013810:Therapeutic Equivalency
D002214:Capsules; D003692:Delayed-Action Preparations; D019469:Indinavir; D016049:Didanosine; D019438:Ritonavir