1st EACS RESISTANCE & PHARMACOLOGY WORKSHOP
October 25 - 29, 2003 Warsaw, Poland
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9TH EUROPEAN AIDS CONFERENCE (EACS) 1st EACS RESISTANCE & PHARMACOLOGY WORKSHOP October 25 - 29, 2003 Warsaw, Poland |
| 4.1 PK and Pharmacodynamics F2/3 - PHARMACOKINETICS (PK) OF SAQUINAVIR/RITONAVIR (SQV/R) ONCE DAILY (OD) IN HIV+ SUBJECTS: COMPARISON WITH STANDARD BD REGIMENS |
| (1) Chelsea and Westminster Hospital, London, UK,2 University of Liverpool, Liverpool, UK,3 Roche, Welwyn, UK |
Background: SQV/r is currently licensed for use at a dosage of 1000/100mg BD. OD regimens may improve adherence to HAART.
Objectives: To investigate the steady-state PK and safety of OD SQV/r at 1600/100 and 2000/100mg in HIV+ patients (pts).
Methods: 15 HIV+ pts (2 females; mean age 42y) were enrolled in a PK study to assess the steady-state exposure to SQV/r (using SQV hard gel capsules, Invirase®) when given at different dosages: 1000/100mg BD, 1600/100mg OD, and 2000/100mg OD. Safety analysis was performed at screening, during the 3 PK days, and follow-up. Blood was drawn pre-dose and 0.5, 1, 2, 3, 4, 6, 8, and 12h following morning and evening doses for BD regimens and at the same time-points plus 24h post-dose for OD regimens. SQV/r concentrations were measured by HPLC-MS/MS.
Results: Mean±SD CD4 cell-count at screening was 383±286/mm3; 11/15 pts had plasma HIV-RNA<50copies/mL. No significant changes in ALT, AST, glucose, total cholesterol and triglycerides were observed. When compared to standard 1000/100mg BD, SQV/r 1600/100mg OD, showed a significant increase in maximum concentration (Cmax, 53%) and decrease in trough concentration (Ctrough, 78%), while 2000/100mg OD a significant increase in Cmax (130%).
| (Table 1; AUC=concentration vs time curve) | |||||
| SQV/r dose (mg) | Fold change [geometric mean (95%CI)] | ||||
| Parameter [geometric mean (95%CI)] | A) 1000/100 BD | B) 1600/100 OD | C) 2000/100 OD | B vs A | C vs A |
| AUC (ng.h/mL) | 23713 (18609,39767) | 19743 (14779,34129) | 33786 (21594,67651) | 0.83 (0.59,1.39) | 1.36 (0.66,3.14) |
| Ctrough | 498 (374,1020) | 108 (70,248) | 263 (61,971) | 0.22 (0.14,0.42) | 0.48 (-0.55,3.20) |
| Cmax | 1796 (1469,2834) | 2740 (2067,4594) | 4132 (3193,6384) | 1.53 (1.13,2.48) | 2.30 (1.72,4.01) |
Conclusions: On SQV/r 2000/100mg OD mean AUC was 36% higher, Cmax 130% higher, but Ctrough 52% lower than the standard 1000/100 mg BD dosage. There was no increased toxicity and 13/15 pts had Ctrough>MEC of 50ng/mL. The 2000/100 OD dosage is a candidate for new clinical trials of OD SQV.
Presenting Author: MD Marta Boffito, Chelsea and Westminster Hospital, St. Stephens AIDS Centre - 369 Fulham Rd, SW10 9NH, London, United Kingdom, Phone: +44 (0)2088466507
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