Table 1.
Study Design—Routes of Administration and Sample Times
| Study Type | Administration Route | Evaluable Subjects | Dose (total mg) | Route | Collection Site | Sampling Times (Plasma and CSF) | |
|---|---|---|---|---|---|---|---|
| Plasma | CSF | ||||||
| PK | IV (n = 4) | 1, 2, 3 | 3.75 mg/kg (HED = 75 mg/m2) (36.99–46.5 mg) | IV port— jugular | IV port | Lumbar port or CSF reservoir | 0, 5, 30, 35, and 45 min and 1, 2, 3, 4, 6, 8, 24, and 48 h |
| PK | 5-AZA IT-V (n = 5) | 2, 4, 5, 6 | 10 mg | CSF reservoir | IV port | Lumbar port | 0, 5, and 30 min and 1, 2, 3, 4, 6, 8, 10, and 24 h |
| PK | 5-AZA IT-L (n = 5) | 2, 4, 5 | 10 mg | Lumbar port | IV port | CSF reservoir | 0, 5, and 30 min and 1, 2, 3, 4, 6, 8, 10, and 24 h |
| PK | 5-AZA + inulin IT-V (n = 3) | 4, 5, 6 | 10 mg 5-AZA, 2 mg inulin | CSF reservoir | IV port | Lumbar port | Plasma: 0, 2, 4, 6, 8, and 10 h CSF: 0, 5, and 30 min and 1, 2, 3, 4, 6, 8, 10, and 48 h |
| MD/PK | IT-C (n = 3) | 8, 9,10 | 10 mg | Cisterna magna | Catheter | Subarachnoid catheter | 0, 5, and 30 min and 1, 2, 3, 4 h Cortical ECF 0–4 h Tissue (Brain, liver, and kidney) |
CSF, cerebrospinal fluid; PK, pharmacokinetics; IV, intravenous; HED, human equivalent dose; 5-AZA, 5-azacytidine; MD, microdialysis; IT-V, intraventricular; IT-L, intralumbar; IT-C, intracisternal.