Pharmacokinetic parameters of U-74006F in humans and rats
| Author | Dose in mg/kg | Administration Route | Plasma Concentration | Half-life in Hours | Side Effects | Steady State After Days | VdArea in L/kg | Excretion |
|---|---|---|---|---|---|---|---|---|
| Fleishaker et al. (1993a) | 0.25–0.50 1.00–2.00 | intravenous infusions over 10 or 30 min at final concentration of 1.5 mg/mL or 0.375 mg/mL, respectively | 20 ng/mL1-a >99% bound to proteins in humans | human 3.7 rat 501-b | local pain at injected site due to vehicle and increased lymphocyte counts at 24–40 min in 2.0 mg/kg group | 3.33 | majority in feces less than 12% in urine1-c | |
| Fleishaker et al. (1993b) | 0.50–1.00 2.00–4.00 6.00–(day) | intravenous infusions every 6 h over 10 or 30 min (multiple dosing) | 20 ng/mL1-a | 35 | as above and increase in liver enzyme activities (alanine transaminase) in 6 mg/kg group | 5 | from 17 to 31 | as above |
| Laizure et al. | 10 | intravenous injections after 0–10– | rat 2.4 | 4.8 | clearance | |||
| (1993) | 20–40 min and 1.5–2.0–3.0–4.0–6.0–8.0 h from injection | brain 1.9 heart 1.6 | 6.1 mL/min | |||||
| liver 1.5 | ||||||||
| Hulst et al. (1994) | 1.5 | single infusions over 10 min | 10 ng/mL1-a | human 8.1 | note1-d | clearance is 25% lower | ||
| 3.0 | 14.7 | in the elderly |
↵1-a Assay limit.
↵1-b Cox et al., 1989.
↵1-c Stryd et al., 1992.
↵1-d Male volunteers: mean age 33 years (from 23 to 42)—mean body weight. 67.4 kg; female volunteers: mean age 70 years (from 65 to 85)—mean body weight 68.2 kg. A gender-related effect for tirilazad pharmacokinetics was noted: clearance was higher in women than in men, probably because of 5-alpha-reductase activity (liver) 5-fold higher in female rats than in male rats (Wienkers et al., 1995).