Table 5.
Reference pharmacokinetic data for nelfinavir, M8 and nelfinavir plus M8 after twice-daily administration of nelfinavir (1250 mg BID).*
| Reference | |||||
|---|---|---|---|---|---|
| Parameter† | [16, 34]‡ n = 10 Intens. PK‡‡ | [31]‡ n = 84 Pop. PK | [19] n = 355 Pop. PK | [22]§** n = 12/12 Intens. PK | [in house data]¶†† n = 5 Intens. PK |
| Nelfinavir | |||||
| AUC24h (h.mg l−1) | 51.0 | 52.0§§ | 48.0§§ | 52.5/55.5** | 41.8† |
| Cmax (mg l−1) | 4 | 8.33 | 3.4 | 3.39/4.25** | 3.9 |
| Cmin, morning (mg l−1) | 2.2 | 1.02 | 1.60 | 1.16/1.24 | 1.30 |
| Cmin, evening (mg l−1) | 0.7 | 0.85 | 1.76/1.35 | 0.65 | |
| M8 | |||||
| AUC24h (h.mg l−1) | 15.2§§ | 24.6/26.7** | 12.9§§ | ||
| Cmax (mg l−1) | 1.1 | 1.76/1.95** | 1.4 | ||
| Cmin, morning (mg l−1) | 0.41 | 0.44/0.48 | 0.39 | ||
| Cmin, evening (mg l−1) | 0.28 | 0.71/0.65 | 0.05 | ||
| Nelfinavir + M8¶¶ | |||||
| AUC24h (h.mg l−1) | 63.2 | 77.1/82.2 | 54.7 | ||
| Cmin, morning (mg l−1) | 2.01 | 1.60/1.72 | 1.69 | ||
| Cmin, evening (mg l−1) | 1.13 | 2.47/2.00 | 0.70 | ||
| M8:nelfinavir ratio¶¶ | |||||
| Ratio for AUC24h | 0.32 | 0.47/0.48 | 0.31 | ||
| Ratio for Cmin, morning | 0.26 | 0.38/0.39 | 0.30 | ||
| Ratio for Cmin, evening | 0.33 | 0.40/0.48 | 0.08 | ||
Reference data were assessed in HIV-infected patients, except for [22] (healthy volunteers).
AUC24h, 24 h area under the concentration–time curve; Cmax, highest observed plasma concentration; Cmin, trough concentration, either in the morning (before the morning dose) or in the evening (before the evening dose).
Median values.
Mean values.
Geometric means.
Reference22 was a two-group study; data for both groups are shown. Mean values for AUC24h were estimated by summing mean AUC12h values reported for the morning dose and evening dose. Cmax values refer to the morning dose.
In-house reference data were retrieved from our own dataset of intensive pharmacokinetic assessments. These data were assessed after intake of nelfinavir with a full breakfast that was identical to the breakfast used in the study, and the same bioanalytical method was used for measurement of drug concentrations (see text).
Reference data were assessed by intensive (intens.) pharmacokinetic (PK) measurements in a limited number of individuals, or by population (pop.) pharmacokinetic approaches.
AUC24h values were obtained by doubling AUC12h values that were reported in the references.
Values for Nelfinavir + M8 and for M8:nelfinavir ratios were derived from the mean values reported for nelfinavir and M8 separately (this is an approximation).