14th Report from: 7th Conference on Retroviruses and Opportunistic Infections, San Francisco, Thursday Feb 3
Pharmacokinetics of the Triple Combination of Saquinavir, Ritonavir, and Efavirenz in HIV-Positive Patients.
C. W.
HENDRIX*, W. D. FISKE, E. J. FUCHS, E. C. REDPATH, D. L. STEVENSON, I. H. BENEDEK, and D. M. KORNHAUSER. Johns Hopkins, Baltimore, MD and DuPont Pharmaceuticals Co., Wilmington, DE.Previous two-way pharmacokinetic (PK) interaction studies with efavirenz (EFV), saquinavir (SQV) and ritonavir (RTV) have shown that EFV decreases plasma levels of SQV, RTV increases plasma levels of SQV, and EFV and RTV increase plasma levels of each other. These interactions are believed to be mediated by induction and inhibition of the 3A4 isozyme of cytochrome P-4S0 (CYP3A4). The present study was performed to determine the PK interaction of the triple combination.
Patients (n=2) receiving SQV (Fortovase) 400 mg q12h and RTV 400 mg q12h entered the study and baseline PK was assessed on Day 0. EFV 600 mg qd was added to the regimen (Days 1-14) and PK was assessed on Day 14. The dose of SQV was then increased to 800 q12 (Days 15-28) and PK was assessed on Day 28.
AUC0-24 Values (SQV and RTV units pgxh/mL, EFV units m◊h)--
| Drug Patient 101 | Drug Patient 102 | |||||||
|
Day 0 |
Day 14 |
Day 28 |
Day 0 |
Day 14 |
Day 28 |
|||
| SQV |
56.3 |
59.2 |
69.9 |
SQV |
62.9 |
67.8 |
92.3 |
|
| RTV |
228.6 |
119.9 |
97.3 |
RTV |
249.5 |
316.2 |
136.1 |
|
| EFV |
- |
303.7 |
402.8 |
EFV |
- |
188.1 |
206.2 |
|
The data indicate that SQV is not affected by EFV when RTV is coadministered. Doubling the SQV dose to 800 mg q12h appears to be unnecessary since it produces a less than proportional increase in SQV AUC0-24, and may affect the PK of RTV and EFV.