Development of an indinavir oral liquid for children.
An indinavir oral liquid was developed and studied. Several oral liquids containing indinavir were prepared and taste tested in eight healthy volunteers. Physical and chemical stability over two weeks were examined, and a randomized, two-way-crossover, single-dose bioequivalence trial was performed in 12 healthy male volunteers. Indinavir 800 mg was given as two 400-mg indinavir capsules (Crixivan) on day 1 and as 80 mL of the indinavir liquid on day 2, or vice versa. A standard breakfast and lunch were given at fixed times, and blood and urine samples were collected at various intervals up to eight hours. The log-transformed area under the concentration-versus-time curve from zero to eight hours (AUC0-8) and maximum plasma concentration (Cmax) for the liquid versus the capsules were compared by using a 90% confidence interval (CI) test (limits, 80-125%), and the time to Cmax (tmax) was compared by using the nonparametric sign test. The liquid selected had an acceptable taste, contained indinavir 10 mg/mL, and was chemically stable for two weeks at 4 degrees C. The 90% CI for the AUC ratio (liquid versus capsules) was 92-99% (mean, 95%); for the Cmax ratio it was 95-106% (mean, 100%). There was no significant difference in tmax between the liquid and capsules. An oral liquid formulation of indinavir was developed that had an acceptable taste, was chemically stable, and was bioequivalent to the commercially available capsule.
Hugen
P W
PW
Department of Clinical Pharmacy, Faculty of Medicine, University Hospital Nijmegen, Netherlands. p.hugen@klinfarm.azn.nl
Burger
D M
DM
ter Hofstede
H J
HJ
Koopmans
P P
PP
Hekster
Y A
YA
D000284:Administration, Oral; D000328:Adult; D002648:Child; D004355:Drug Stability; D017320:HIV Protease Inhibitors / Q000008:administration & dosage*; D006801:Humans; D019469:Indinavir / Q000008:administration & dosage* / Q000737:chemistry; D008297:Male; D008875:Middle Aged; D013810:Therapeutic Equivalency
D017320:HIV Protease Inhibitors; D019469:Indinavir