Table 1. Pharmacokinetic parameters of linezolid and AZD5847 in primates.
Shown are pharmacokinetic parameters of linezolid and AZD5847 in cynomolgus macaques and in humans at clinically used doses (linezolid) (22) or projected efficacious doses (AZD5847) (24). Cmax: peak plasma concentration; Tmax: time to peak plasma concentration; AUC[0–24]: Area Under the Curve from 0 to 24h post-dose; T1/2: elimination half-life; q.d.: once daily; b.i.d.: twice daily.
| Cynomolgus macaques | TB patients | ||||||||
|---|---|---|---|---|---|---|---|---|---|
| dose (frequency) | Cmax | Tmax | AUC[0–24] | T1/2 (elim) | dose (frequency) | Cmax | Tmax | AUC[0–24] | T1/2 (elim) |
| mg/kg | μg/ml | h | μg*h/ml | h | mg | μg/ml | h | μg*h/ml | |
| Linezolid | |||||||||
| 10 (single dose) | 1.8–4.2 | 4 | 27–36 | 5.7–6.3 | 600 (q.d.) | 12–21 | 1–4 | 65–125 | 2.4–3.9 |
| 30 (single dose) | 14–15 | 4 | 121–198 | 3–4 | 600 (b.i.d.) | 12–25 | 1–4 | 80–172 | 3.0–5.8 |
| AZD5847 | Healthy Volunteers | ||||||||
| at steady state | mean (%CV) | range | mean (%CV) | mean (%CV) | |||||
| 10 (single dose) | 3.3 | 4 | 35–40 | 5.2–5.4 | 400 (b.i.d.) | 5.9 (12.6) | 2–5 | 48 (15) | 8.7 (14.40) |
| 20 (single dose) | 1.7–3.2 | 4–10 | 23–37 | 7.7–11.2 | 800 (b.i.d.) | 10.7 (8.6) | 2–4 | 90 (9) | 10.0 (21.8) |