Table 4. Pharmacokinetic parameters of vorinostat (and its metabolites) given orally TID for 14 days or 3 days in combination with idarubicin given at a dose of 9 or 12 mg/m2 IV daily for 3 days.
| Vorinostat Metabolites | ||||||||
|---|---|---|---|---|---|---|---|---|
|
| ||||||||
| Dose and Schedule of Vorinostat | N | Vorinostat Mean Cmax (μM) | Vorinostat Median Cmax (Range) | Vorinostat Median Tmax (h) | Acid Mean Cmax (SD) | Acid Mean Tmax | Glucuronide Mean Cmax (SD) | Glucuronide Mean Tmax |
|
| ||||||||
| 100 mg TID for 14 days | 11 | 0.554 | 0.445 (0.19 - 1.53) | 2.5 | 2.13 (0.88) | 3.3 | 2.16 (2.1) | 2.8 |
| 100 mg TID for 3 days | 3 | 0.688 | 0.331 (0.23 - 1.51) | 2 | 1.97 (0.9) | 2.3 | 1.21 (0.14) | 2.2 |
| 200 mg TID for 3 days | 3 | 0.522 | 0.443 (0.41 - 0.71) | 1 | 3.08 (0.58) | 2.3 | 1.77 (0.18) | 2.3 |
| 300 mg TID for 3 days | 4 | 0.991 | 0.998 (0.57 - 1.40) | 2.5 | 3.19 (1.35) | 2.8 | 3.33 (1.8) | 2.5 |
| 400 mg TID for 3 days | 10 | 1.66 | 1.55 (0.91 - 2.64) | 2.25 | 4.23 | 1 | 4.52 | 1 |
| 500 mg TID for 3 days | 5 | 2.02 | 1.62 (1.61 - 2.84) | 3 | ||||
N represents the total number of patients at each dose and schedule of vorinostat. Cmax = the maximum plasma concentration reached on each dose and schedule. Cmax is expressed in micromolar (μM). Tmax = the time point at which the maximum plasma concentration was reached. Tmax is expressed in hours. SD = standard deviation from the mean value of the samples. Two metabolites of vorinostat were measured in only the first 19 patients (due to limited reagents) – the ‘acid’ metabolite and the ‘glucuronide’ metabolite. The acid metabolite is 4-Anilino-4-oxobutanoic acid. The glucuronide metabolite is vorinostat-glucuronide. The columns labeled ‘Acid’ and ‘Glucuronide’ refer to these metabolites, respectively. At the 400 mg dose, vorinostat metabolites were measured in only 1 patient. At the 500 mg dose, metabolites were not measured in any patients.