13th Annual Conference of the British HIV Association 29 March–1 April 2007, Brighton, UK

SAQUINAVIR/RITONAVIR (SQV/r) PHARMACOKINETICS (PK) IN THE PRESENCE OF OMEPRAZOLE (OMZ): HEALTHY VOLUNTEERS AND HIV-INFECTED PATIENT DATA ANALYSIS

HIV Med 2007; 8(Suppl. 1):5 (abstract no. O19)

Kasha Singh¹, Alan Winston², Laura Dickinson³, David Back³, Carl Fletcher¹, Anton Pozniak¹, Graeme Moyle¹, Mark Nelson¹, Brian Gazzard¹, Dilruwan Herath⁴ and Marta Boffito^1
1Chelsea and Westminster NHS Foundation Trust, London, UK, ²St Mary’s Hospital, London, UK, ³University of Liverpool, Liverpool, UK, ⁴Roche, London, UK

BACKGROUND: Studies have described reduced absorption of certain protease inhibitors when given with agents known to increase gastric pH. To avoid risking low drug concentrations leading to virological failure these studies are performed in healthy volunteers (HV). HIV+ subjects may have concurrent conditions altering gastric pH and drug absorption. We investigated the safety and PK of SQV/r given with OMZ in HV and then in HIV+.

METHODS: In HV SQV/r 1000/100 mg was administered bd for 15 days. On days 11–15, subjects received OMZ 40 mg qd with SQV/r. HIV+ on SQV/r bd-containing regimens were randomized to group A (SQV/r and OMZ simultaneously days 2–8, wash out days 9–14, OMZ two hours before SQV/r (days 15–22) or group B (OMZ two hours before SQV/r days 2–8, wash out days 9–14, SQV/r and OMZ simultaneously days 15–22). Steady-state SQV/r 12 h PK was assessed before and after adding OMZ. PK parameters were calculated using non-compartmental modelling (WinNonlin®). Within-subject changes in PK parameters were evaluated by geometric mean (GM) ratios and 90% confidence interval.

RESULTS: Eighteen (12 male) HV and 12 (11 male) HIV+ completed the studies. GM SQV for area under time-concentration curve (AUC; ng/h/mL), trough concentration (ng/mL) and maximum concentration (ng/mL) all increased significantly in HV and HIV+ with addition of OMZ. AUC increased by 82% in HV and 54% in HIV+. Staggered administration of OMZ in HIV+ also led to a significant increase in all SQV PK parameters (AUC increase 67%). No grade 3/4 toxicity occurred.

CONCLUSIONS: In the presence of OMZ total SQV exposure is significantly increased in both HV and in HIV+. The mechanism of interaction requires elucidation. Despite the increase in SQV exposure, no short-term toxicities were observed.

2007-03-29
O19

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