Table I.
Single-dose noncompartmentalized and 1-compartment pharmacokinetic parameters for pentoxifylline (PTX) and 1-(5′-hydroxyhexyl)-3,7-dimethylxanthine (M-1) from study day 1.
| Noncompartmental Analysis |
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|---|---|---|---|---|---|---|---|---|
| Dose Level | Cmax, ng/mL | Tmax, h | Cl/FNC, L/kg·h | VdNC/F, L/kg | t1/2, h | AUC0–∞, ng/mL·h | PTX + M-1 AUC, μM×h | M-1/PTX AUC Ratio |
| 1 PTX (n = 6) | ||||||||
| Median | 315 | 0.4 | 6.1 | 6.2 | 0.7 | 622 | 6.4 | 1.7 |
| Range | 83–2582 | 0.3–2.0 | 1.8–13.6 | 1.5–16.9 | 0.5–1.2 | 252–1819 | 1.9–10.5 | 0.6–2.1 |
| M-1 (n = 6) | ||||||||
| Median | 632 | 0.3 | – | – | 0.8 | 914 | – | – |
| Range | 192–1190 | 0.3–0.5 | – | – | 0.6–1.4 | 279–1629 | – | – |
| 2 PTX (n = 5) | ||||||||
| Median | 797 | 0.5 | 1.5 | 4.9 | 1.0 | 3428 | 21.2 | 1.7 |
| Range | 342–2924 | 0.3–0.5 | 0.9–23.5 | 1.5–7.3 | 0.2–2.3 | 213–5426 | 4.3–62.6 | 0.7–4.6 |
| M-1 (n = 5) | ||||||||
| Median | 833 | 1.0 | – | – | 1.3 | 2477 | – | – |
| Range | 435–2715 | 0.5–3.0 | – | – | 0.4–2.6 | 785–12,055 | – | – |
| 3 PTX (n = 6) | ||||||||
| Median | 3016 | 0.8 | 0.9 | 1.0 | 0.9 | 8416 | 58.8 | 1.0 |
| Range | 1025–5230 | 0.3–1.0 | 0.5–3.8 | 0.6–3.4 | 0.2–2.3 | ,1771–13,653 | 20.0–96.4 | 0.4–2.2 |
| M-1 (n = 6) | ||||||||
| Median | 2607 | 1.0 | – | – | 1.3 | 8000 | – | – |
| Range | 803–3391 | 0.5–2.0 | – | – | 0.5–3.1 | 1696–13,235 | – | – |
| 4 PTX (n = 6) | ||||||||
| Median | 3235 | 0.5 | 0.9 | 2.3 | 1.3 | 10,347 | 49.4 | 0.4 |
| Range | 2007–8270 | 0.3–1.0 | 0.5–4.0 | 1.0–6.7 | 0.6–3.5 | ,2080–15,922 | 10.1–83.5 | 0.04–0.8 |
| M-1 (n = 5) | ||||||||
| Median | 1424 | 1.0 | – | – | 1.3 | 6037 | – | – |
| Range | 341–2169 | 0.5–2.0 | – | – | 0.7–3.4 | 727–8193 | – | – |
| 1-Compartment Model Analysis |
|||
|---|---|---|---|
| Cl/F1-C, L/kg·h | Vd1-C/F, L/kg | AUC0–∞, ng/mL·h | |
| 1 PTX (n = 5) | |||
| Median | 4.3 | 4.9 | 749 |
| Range | 4.0–14.2 | 4.3–15.9 | 241–839 |
| M-1 (n = 6) | |||
| Median | – | – | 701 |
| Range | – | – | 209–1637 |
| 2 PTX (n = 4) | |||
| Median | 1.4 | 4.6 | 3701 |
| Range | 1.0–5.6 | 2.0–9.4 | 893–5268 |
| M-1 (n = 4) | |||
| Median | – | – | 4684 |
| Range | – | – | 1258–10,969 |
| 3 PTX (n = 6) | |||
| Median | 0.9 | 1.0 | 7721 |
| Range | 0.5–5.0 | 0.5–2.4 | 1333–13,623 |
| M-1 (n = 6) | |||
| Median | – | – | 5488 |
| Range | – | – | 976–14,238 |
| 4 PTX (n = 4) | |||
| Median | 1.8 | 1.9 | 5263 |
| Range | 0.6–5.5 | 0.9–7.2 | 1510–13,836 |
| M-1 (n = 4) | |||
| Median | – | – | 2879 |
| Range | – | – | 372–8488 |
Cmax = maximum plasma concentration; Tmax = time to Cmax; Cl/FNC = noncompartmental oral clearance; VdNC/F = volume of distribution based on terminal slope (λz); t1/2 = half-life; AUC0–∞ = area under the plasma concentration–time curve from time 0 to infinity; Cl/F1-C = oral clearance from 1-compartment model; Vd1-C/F = volume of distribution from 1-compartment model.