Table 2.
Levels of the four OATP1B1 biomarkers, HDA, TDA, CP‐I, and CP‐III, in each treatment group
| Treatment | Pravastatin + placebo (N = 16) | Pravastatin + cyclosporine (N = 16) | ||||||
|---|---|---|---|---|---|---|---|---|
| Biomarker | HDA | TDA | CP‐I | CP‐III | HDA (fold change) | TDA (fold change) | CP‐I (fold change) | CP‐III (fold change) |
| C0 (nM) | 60.1 ± 37 | 55 ± 44 [N = 11] | BLOQ in most samples | BLOQ in most samples | 84 ± 33 ** [N = 11] (1.5) | 68 ± 26 [N = 11] (1.6) | BLOQ in most samples | BLOQ in most samples |
| Cmax (nM) | 90.6 ± 77.3 | 94.7 ± 118.5 | 1.04 ± 0.45 | 0.15 ± 0.039 |
155 ± 55.1** (2.1) |
149 ± 71.0* (2.2) |
2.16 ± 0.71**** (2.2) |
0.24 ± 0.05**** (1.7) |
| Cavg (nM) | 56.4 ± 35.1 | 53.3 ± 49.3 | 0.83 ± 0.36 | a0.12 ± 0.03 |
100 ± 33.3**** (2.0) |
86.0 ± 35.8** (2.0) |
1.51 ± 0.56**** (1.9) |
a0.17 ± 0.03**** (1.5) |
| AUClast (nM·hour) | 649 ± 346 | 593 ± 489 | 9.4 ± 4.2 | a1.21 ± 0.46 |
1,070 ± 357**** (1.8) |
902 ± 378** (1.9) |
15.5 ± 6.7**** (1.7) |
a1.68 ± 0.44*** (1.9) |
Arithmetic mean ± SD for each biomarker's parameters in the two treatment groups are reported in this table. Paired t‐test was used to determine the significance of each parameter between the treatment groups. Number in parentheses is the fold increase between pravastatin plus cyclosporin A group over pravastatin plus placebo group. A total of 16 subjects were available for biomarker analysis; however, for some biomarkers, the levels are below the level of quantification; the number in square brackets is number of subjects available for the analysis.
AUClast, area under the curve from time 15 minutes after second dose of cyclosporin A administration or placebo to 12 hours; BLOQ, below the limit of quantification; C0, concentrations at time 0, baseline (this level is taken after 12 hours from cyclosporin A administration from the night before and right before the second dose of cyclosporin A administration); Cavg, average concentrations from the collected samples, 15 minutes after second dose of placebo or cyclosporin A administration; Cmax, maximum concentrations from the collected samples, 15 minutes after second dose of placebo or cyclosporin A administration; CP, coproporphyrin; HDA, hexadecanedioate; OATP, organic anion‐transporting polypeptide; TDA, tetradecanedioate.
Overall, CP‐III are very low and many timepoints have below quantification levels.
The significant P values are: *P < 0.05; **P < 0.005; ***P < 0.0005; ****P < 0.0001.