Table 3.
Predicted changes in metabolic parameters based on observed amprenavir and efavirenz AUCs.
|
Amprenavir AUC in plasma (μg*h/mL)a |
Predicted change in metabolic parameter (associated 95% confidence intervals) |
||||
|---|---|---|---|---|---|
| HDL-c, day 14b | TCHC, day 14c | TG, day 14d | GLU, day 21e | CPEP, day 14f | |
| 0.5 | 7.44 | −0.17 | 3.04 | 1.87 | −0.38 |
| 4.0 | 3.10 | 0.12 | 20.96 | 1.25 | −0.04 |
| 8.0 | −1.86 | 0.46 | 41.45 | 0.54 | 0.34 |
| 14.0 | −9.29 | 0.96 | 72.18 | −0.52 | 0.92 |
|
Efavirenz AUC in plasma (mg*h/mL) |
|||||
| 20.0 | 0.64 | -- | 35.78 | -- | -- |
| 38.0 | 2.29 | -- | 24.79 | -- | -- |
| 170.0 | 14.34 | -- | −55.83 | -- | -- |
Representative plasma amprenavir AUCs were derived from A5043 as follows: 0.5 was the minimum AUC, 4.0 represents the median AUC on days 14 and 21, 8.0 represents the median AUC on day 0, and 14.0 represents the maximum AUC on day 14. For efavirenz AUCs: 20.0, 38.0 and 170.0 represent the minimum, median and maximum values obtained on A5043 subjects.
HDL-cholesterol, mg/dL. The estimated regression equations were: (1) for changes on day 14, 19.43 − (0.26*baseline HDL-c) − 1.24 (0.97*day 14 amprenavir AUC), and (2) for additional changes on day 21, 8.81 − (0.23*baseline HDL-c) + (0.09*day 14 efavirenz AUC). In generating predicted values, baseline median HDL-c (43.0) was used. (Baseline values were predictive of day 14 changes from baseline.)
Ratio of total:HDL-cholesterol, change from baseline on day 14. The estimated regression equation was: 0.57 − (0.22*baseline TCHC) + (0.08*day 14 amprenavir AUC). Baseline median TCHC (3.57) was used.
Triglycerides, change from baseline on day 14, mg/dL. The estimated regression equations were: (1) as a function of amprenavir AUCs, 27.45 − (0.34*baseline TG) + (5.12*day 14 amprenavir AUC), and (2) as a function of efavirenz AUCs, 68.76 − (0.26*baseline TG) − (0.61*day 14 efavirenz AUC). Baseline median TG (79.5) was used.
Blood glucose, change from day 14 on day 21, mg/dL. The estimated regression equation was: 1.95 − (0.18*day 14 amprenavir AUC). Baseline GLU, not a significant predictor, was not included as a model covariate.
C-peptide, change from baseline on day 14, ng/mL. The estimated regression equation was: 0.09 − (0.34*baseline CPEP) + (0.10*day 14 amprenavir AUC). Baseline median CPEP (1.5) was used.