Saquinavir soft-gel capsules (Fortovase) give lower exposure than expected, even after a high-fat breakfast.
BACKGROUND
The soft-gel capsule (sgc) of saquinavir has been developed in order to improve the poor oral bioavailability of the original hard-gel capsules. However, in a Dutch study population using saquinavir-sgc plasma levels were lower than expected. We hypothesised that this was caused by differences in the amount of fat in the meals of the study populations.


METHODS
8-h steady-state plasma curves after observed ingestion of 1200 mg saquinavir-sgc were recorded, concomitantly with a normal breakfast (600 kcal, 33% fat) on the first day, and a high-fat breakfast (1040 kcal, 54% fat) on the second day. Additionally, a comparison was made between saquinavir hard-gel capsules and saquinavir-sgc with or without grapefruit juice (n = 1). Furthermore, a comparison between saquinavir-sgc and ritonavir + saquinavir-sgc 400/400 mg bid was made (n = 1).


RESULTS
Although saquinavir exposure was improved by fat, grapefruit juice or ritonavir, exposure to saquinavir for all recorded curves was lower than expected. A large proportion of trough concentrations was below the efficacy threshold.


CONCLUSIONS
Intake of squinavir-sgc with high-fat meals or grapefruit juice may improve the pharmacokinetic profile. However, plasma concentrations may then still be lower than expected and insufficient for good antiviral efficacy. Probably the only way to reach adequate saquinavir concentrations is by combining saquinavir with ritonavir.
Hugen
P W H
PW
Department of Clinical Pharmacy, University Medical Centre Nijmegen, 533 Dept. Clinical Pharmacy, 6500 HB Nijmegen, The Netherlands. p.hugen@klinfarm.azn.nl
Burger
D M
DM
Koopmans
P P
PP
Stuart
J W T Cohen
JW
Kroon
F P
FP
van Leusen
R
R
Hekster
Y A
YA
D000328:Adult; D019540:Area Under Curve; D002214:Capsules; D002626:Chemistry, Pharmaceutical; D004041:Dietary Fats / Q000493:pharmacokinetics*; D018565:Food-Drug Interactions; D006801:Humans; D008297:Male; D008875:Middle Aged; D019258:Saquinavir / Q000097:blood* / Q000493:pharmacokinetics; D018709:Statistics, Nonparametric
D002214:Capsules; D004041:Dietary Fats; D019258:Saquinavir