Pharmacokinetic interaction between indinavir and darunavir with low-dose ritonavir in healthy volunteers.
OBJECTIVE
To investigate the potential for a pharmacokinetic interaction between darunavir (DRV, TMC114, Prezista), indinavir (IDV, Crixivan) and low-dose ritonavir (RTV, Norvir).


METHODS
In three 7-day sessions, 17 HIV-negative healthy volunteers received treatment A (DRV/r 400/100 mg b.i.d.), treatment B (IDV/r 800/100 mg b.i.d.) and treatment C (DRV/r 400/100 mg b.i.d. + IDV 800 mg b.i.d.). On day 7, full pharmacokinetic profiles of DRV, IDV and RTV were determined. Safety and tolerability were also assessed.


RESULTS
Based on the least-squares means ratios, the steady-state exposure (area under the curve, AUC(12h)) and plasma concentrations (C(min) and C(max)) of IDV were increased by 23, 125 and 8%, respectively, when DRV was co-administered. The co-administration of IDV with DRV/r resulted in increases of 24, 44 and 11% for, respectively, DRV AUC(12h), C(min) and C(max), compared with administration of DRV/r alone. Eight volunteers discontinued due to an adverse event. Overall, adverse events and laboratory abnormalities were more commonly reported during treatments including IDV.


CONCLUSIONS
When used in combination with DRV/r, dose adjustment of IDV from 800 mg b.i.d. to 600 mg b.i.d. may be warranted in cases of intolerance.
Sekar
Vanitha
V
Tibotec Inc., Yardley, Pa., USA. vsekar @ tibus.jnj.com
Lefebvre
Eric
E
De Marez
Tine
T
De Pauw
Martine
M
De Paepe
Els
E
Vangeneugden
Tony
T
Hoetelmans
Richard M W
RM
D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D000069454:Darunavir; D004347:Drug Interactions; D005260:Female; D064368:Healthy Volunteers; D006801:Humans; D019469:Indinavir / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D008297:Male; D010949:Plasma / Q000737:chemistry; D019438:Ritonavir / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D013449:Sulfonamides / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D055815:Young Adult
D019380:Anti-HIV Agents; D013449:Sulfonamides; D019469:Indinavir; D019438:Ritonavir; D000069454:Darunavir