Table II.
Pharmacokinetic Parameters of Tanespimycin*.
| Dose, mg/m2 | Statistic | Cmax (ng/ml) | Tmax (h) | AUCtot (ng/ml* h) | t1/2 (h) | CL (l/h) |
|---|---|---|---|---|---|---|
| 150 (n = 4) | Mean | 2403 | 0·99 | 5592·3 | 2·19 | 54·92 |
| Median (min–max) | 2435 (1470–3220) | 0·99 (0·87–1·08) | 5517·3 (4720·8–7020·8) | 2·06 (1·45–3·41) | 56·40 (43·44–63·15) | |
| 220 (n = 9) | Mean | 4590 | 1·03 | 9405·0 | 2·68 | 46·77 |
| Median (min–max) | 4050 (3080–8540) | 1·00 (0·98–1·25) | 9505·9 (4521·0–15,848·8) | 4·40 (1·18–2·36) | 74·98 (19·31–47·90) | |
| 275 (n = 3) | Mean | 6820 | 1·03 | 13,802·8 | 2·96 | 39·63 |
| Median (min–max) | 7065 (4720–8530) | 1·00 (0·98–1·15) | 14,250·0 (11,867·5–15,708·5) | 2·91 (1·58–5·16) | 39·74 (28·39–49·80) | |
| 340 (n = 7) | Mean | 8751 | 0·99 | 17,936·1 | 3·10 | 37·20 |
| Median (min–max) | 7600 (6740–14,600) | 0·98 (0·50–1·33) | 15,615·1 (10,380·6–32,100·5) | 3·30 (1·80–4·30) | 36·80 (22·70–54·00) | |
| 420 (n = 3) | Mean | 7133 | 1·58 | 23,069·7 | 3·00 | 41·50 |
| Median (min–max) | 8500 (4470–7570) | 2·28 (1·00–1·48) | 36,003·7 (13,124·4–24,482·8) | 4·08 (2·30–2·93) | 69·41 (22·05–34·87) | |
| 525 (n = 3) | Mean | 9920 | 2·00 | 29,639·0 | 2·60 | 57·0 |
| Median (min–max) | 10,600 (5680–12,800) | 2·20 (2·00–2·80) | 28,683·0 (17,375·0–43,816·0) | 2·60 (2·20–3·00) | 57·0 (35·6–78·3) |
AUCtot, area under the concentration time curve from time zero to infinity; CL, total systemic clearance; Cmax, maximum plasma concentration; t1/2, half-life; Tmax, time to maximum plasma concentration.
*
Distributive volume values and clearance reported have been corrected for body surface area.