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Cardiello Peter G.; Monhaphol, Tarkika; Mahanontharit, Apicha; van Heeswijk, Rolf P.; Burger, David; Hill, Andrew; Ruxrungtham, Kiat; Lange, Joep M.; Cooper, David A.; Phanuphak, Praphan
JAIDS Journal of Acquired Immune Deficiency Syndromes: April 1st, 2003

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 oncedaily 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 (Cmax), minimum concentration (Cmin), time to Cmax, 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 (p = .056). Intersubject variability resulted in 4 of 13 subjects on the SQV SGCs and 2 of 13 subjects on the SQV HGCs having a Cmin below the minimum effective concentration of 0.05 mg/L.

Conclusion: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.

Financial support for this study was provided by Roche-Bangkok, Thailand. AZT/3TC (Combivir) was purchased by HIVNAT-Bangkok, Thailand, ddI (Videx) and d4T (Zerit) were provided by Bristol Myers Squibb-Bangkok, Thailand. SQV SGCs (Fortovase) and SQV HGCs (Invirase) were supplied by Roche-Bangkok, Thailand. RTV (Norvir) was purchased by Roche-Bangkok, Thailand.

Address correspondence and reprint requests to David M. Burger, Department of Clinical Pharmacy, 533 University Medical Centre Nijmegen, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands; e-mail:

Manuscript received September 17, 2002; accepted January 14, 2003.

© 2003 Lippincott Williams & Wilkins, Inc.