If this is not your name, click here.
| | If this is not your name, click here. | | |
| | Contact Us | Order Now | Journals | Bookstore | Register a colleague | | |
| |  DG DISPATCH - ICDT-HIV: Once Daily Azapeptide Protease Inhibitor As Effective As Viracept (Nelfinavir) Three Times Daily By David Jack Special to DG News
GLASGOW, SCOTLAND -- October 24, 2000 -- New data from a pharmacokinetic/pharmacodynamic subset analysis show that Bristol-Myers Squibb’s novel azapeptide protease inhibitor, BMS-232632, given once a day is at least as effective as nelfinavir (Viracept, Roche) given three times a day. One of the main disadvantages of HAART (highly active antiretroviral therapy) is the large pill burden imposed on patients, and treatment adherence is a major problem. Many companies are trying to solve this problem by developing either effective combination preparations or drugs with pharmacokinetic properties which allow them to be given once daily. Previously, results from BMS's 007 trial were presented in September at the 40th ICAAC (Interscience Conference on Antimicrobial Agents and Chemotherapy) meeting in Toronto and showed that BMS-232632 was a safe and effective protease inhibitor. At the 5th International Congress on Drug Therapy in HIV Infection in Glasgow, Dr E O'Mara, Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, New Jersey, presented the pharmacokinetic data. The study took the form of a randomized, parallel, comparator trial versus nelfinavir. BMS-232632 was given once daily without food to HIV-positive patients at doses of either 200, 400 or 500 mg once daily. During the first two weeks, patients were given BMS-232632 as monotherapy and then as combination therapy with two nucleosides (d4T twice daily and ddI once daily). A further 49 patients received nelfinavir 750 mg three times daily. Blood samples were collected from 31 patients and 29 patients were subjected to detailed pharmacokinetic analysis on days 1 and 29. The dose increase was in the ratio 1: 2: 2.5 while the observed increase in area under the plasma concentration curve (AUC) on day 29 was in the ratio 1: 1.8 : 2.1 while that in the maximum plasma concentration (Cmax) was 1 : 1.7 : 2.2. There was no significant increase in the plasma half-life (t1/2) which ranged from 4.9 to 6.1 h. HIV RNA measurements were carried out to monitor the efficacy of treatment in terms of the fall in viral load. It was found that there was a mean fall in the number of HIV RNA copies of log 1.84 between day 1 and day 29. There was no significant difference in the magnitude of this fall produced by the different doses of BMS-232632 or nelfinavir. According to Dr O'Mara: "These results confirm that BMS-232632 is a safe and effective protease inhibitor with a great potential for introduction as the first protease inhibitor suitable for once-daily use."
|
