New PK data on Salvage Regimen:
June 8, 1999
I just returned from a meeting conducted by Glaxo wellcome for a community group. At this meeting Steve Piscatelli from the NIH reported, for the first time publicly, PK data on combining ritonavir (RTV) 200 mg bid or nelfinavir (NFV) at full dose (1250 mg bid) with ampranavir (APV) and efavirenz (EFV) in a salvage study. The actual clinical data was not available yet but is
expected to be presented possibly by ICAAC. However, the pharmacokinetics (PK) were discussed. EFV significantly reduces APV blood levels when combined at full doses. However, when combining full dose APV and full dose EFV with 200 mg bid RTV -- APV AUC doubled, APV Cmin increased 5-7 fold and APV Cmax remained the same. This means that RTV prevented the reduced APV blood levels when using EFV with APV. This presents a potentially potent salvage regimen for individuals who are NNRTI naive. It also allows you to combine APV with EFV without reducing APV blood levels.
When combining 1250 mg nelfinavir with full doses of
APV and EFV the same effects were seen but it appears as though additional
nelfinavir diaarhea may result and the pill count is significant.
In addition GW thinks that 1200 mg once daily with RTV 200 or 300 mg once daily may be a once a day regimen. But clinical studies must first be conducted so its not recommended to go out and do this yet. In this situation the RTV allows APV Cmin to approximate APV Cmin when used in its standard dosing regimen 1200 mg bid thus possibly permitting once daily dosing.