Pharmacokinetics of once-daily saquinavir hard-gelatin capsules and saquinavir soft-gelatin capsules boosted with ritonavir in HIV-1-infected subjects.
OBJECTIVE
To investigate the pharmacokinetics of once-daily saquinavir (SQV) hard-gelatin capsule (HGC)/ritonavir (RTV), 1600/100 mg, compared with once-daily SQV soft-gelatin capsule (SGC)/RTV, 1600/100 mg.


METHODS
We evaluated 13 randomly selected HIV-1-infected subjects taking once-daily SQV SGC/RTV, 1600/100 mg, plus dual nucleoside reverse transcriptase inhibitors (NRTIs) in this pharmacokinetic (PK) substudy. Subjects took 1 week of SQV HGC/RTV and NRTIs, followed by steady-state SQV PK determinations. Subjects then changed to SQV SGC/RTV and NRTIs for 1 week, followed again by steady-state SQV PK determinations. Area under the plasma concentration versus time curve (AUC), maximum concentration (C(max)), minimum concentration (C(min)), time to C(max), and elimination half-life were calculated.


RESULTS
There was no significant difference in AUC values between HGCs and SGCs, with a median (plus interquartile range [IQR]) of 50.0 (42.6-71.5) versus 35.5 (28.0-50.2) mg/L/h, respectively ( =.056). Intersubject variability resulted in 4 of 13 subjects on the SQV SGCs and 2 of 13 subjects on the SQV HGCs having a C(min) below the minimum effective concentration of 0.05 mg/L.


CONCLUSIONS
Once-daily SQV HGCs, 1600 mg, boosted with once-daily RTV, 100 mg, resulted in PK parameters that were similar to those observed with 1600 mg of SQV SGC/100 mg RTV once daily. Once-daily SQV HGC/RTV, 1600/100 mg, may be easier to use in developing countries and may increase access where drug costs can be less, the capsule size is smaller, and the need for refrigeration is lessened.
Cardiello
Peter G
PG
HIV Netherlands Australia Thailand Collaboration, The Thai Red Cross AIDS Research Centre, Bangkok, Thailand.
Monhaphol
Tarkika
T
Mahanontharit
Apicha
A
van Heeswijk
Rolf P
RP
Burger
David
D
Hill
Andrew
A
Ruxrungtham
Kiat
K
Lange
Joep M
JM
Cooper
David A
DA
Phanuphak
Praphan
P
D000284:Administration, Oral; D019540:Area Under Curve; D002214:Capsules; D002626:Chemistry, Pharmaceutical; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D015658:HIV Infections / Q000188:drug therapy*; D017320:HIV Protease Inhibitors / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D015497:HIV-1; D006801:Humans; D019438:Ritonavir / Q000627:therapeutic use*; D019258:Saquinavir / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use*
D002214:Capsules; D017320:HIV Protease Inhibitors; D019258:Saquinavir; D019438:Ritonavir