Triple PI interactions: atazanavir increases saquinavir levels in ritonavir-boosted once-daily combination
3 April 2004. Related: Conference reports, PK and drug interactions, CROI 11 (Retrovirus) 2004.
Simon Collins, HIV i-Base
Marta Boffito and colleagues from the Chelsea and Westminster Hospital in London reported a synergistic boosting interaction between 300mg atazanavir (ATV, Reyataz) and 1600mg saquinavir hard gel capsule (SQV, Invirase) when both boosted by 100mg ritonavir (RTV, Norvir) in a once daily combination.
Twenty HIV-positive patients (two women, 18 men), mean age 41 years, median CD4 442 cells/mm3, were administered SQV/RTV 1600/100mg once daily with a 20g fat meal. Atazanavir 300mg once daily was added to the regimen on day two for 30 days, and intensive PK testing was performed at day one and 11 days after atazanavir was added.
Pharmacokinetic results for saquinavir and atazanavir are shown below:
| Geometric mean [95% CI] | |||
| SQV (+ RTV) | SQV (+ATV/RTV) | ATV (+SQV/RTV) | |
| Ctrough (ng/mL) | 87 [72–139] | 184 [140–311] | 767 [577–1427] |
| Cmax (ng/mL) | 2756 [2219–4551] | 3923 [333–5350] | 4982 [333–5350] |
| AUC0-24 (ng.h/mL) | 18,270 [14,951–30,357] | 29,445 [14,951–30,357] | 51,036 [44,369–64,591] |
Geometric mean ratios (GMR) showed statistically significant increases in SQV levels with, compared to without, atazanavir of 112% in Ctrough (GMR 2.12; 95%CI: 1.72 to 3.50), of 42% in Cmax (GMR 1.42; 95%CI: 1.24 to 1.94) and 60% increases in AUC (GMR 1.60; 95% CI 1.35 to 2.43). ATV concentrations were similar to those seen in ritonavir-booted atazanavir regimens without saquinavir.
No significant changes in ALT, AST, glucose, total cholesterol and triglycerides were observed. Total and indirect bilirubin increased by five times after 10 days of atazanavir therapy (median, range: 36, 11-139, and 32, 9-128 mol/L, respectively. Four patients developed scleral icterus and two developed jaundice.
Reference:
Boffito M, Kurowski M, Kruse G et al. Atazanavir enhances saquinavir hard gel concentrations in a ritonavir-boosted once daily regimen. 11th CROI 2004, Abstract 607.