Bibliographic Details
| Title: |
Estimation of Serum-Free 50-Percent Inhibitory Concentrations for Human Immunodeficiency Virus Protease Inhibitors Lopinavir and Ritonavir |
| Authors: |
Hickman, Dean, Vasavanonda, Sudthida, Nequist, George, Colletti, Lynn, Kati, Warren M., Bertz, Richard, Hsu, Ann, Kempf, Dale J. |
| Source: |
Antimicrobial Agents and Chemotherapy; August 2004, Vol. 48 Issue: 8 p2911-2917, 7p |
| Abstract: |
ABSTRACTUsing measured free fraction and 50% inhibitory concentration (IC50) values for the human immunodeficiency virus protease inhibitors lopinavir (LPV) and ritonavir (RTV) in tissue culture media with various protein concentrations ranging from 5 to 50%, we estimated serum-free IC50values for each drug. The range of serum-free IC50values (0.64 to 0.77 ng/ml for LPV and 3.0 to 5.0 ng/ml for RTV) did not exhibit a trend with increasing protein concentrations, despite a 10-fold difference in the free fraction value (0.006 to 0.063) for LPV and a 5-fold difference in the free fraction value (0.013 to 0.057) for RTV. The mean serum-free IC50by the MTT-MT4 assay (0.69 ng/ml for LPV and 4.0 ng/ml for RTV) may be the most accurate parameter for the estimation of the inhibitory quotient (IQ), a relative measure of in vivo potency defined as the ratio of the minimal free drug concentration in plasma (Ctrough,free) for a specific patient population and the serum-free IC50. Using this approach, we calculated the average IQs for protease inhibitor-naìˆve patients for LPV and RTV to be 67 and 5.6, respectively. |
| Database: |
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