Table 7.
Diazepam: systemic physiological parameters of SpO2 (%), heart rate (bpm), and respiration rate (ipm) in diazepam and BPEW vehicle progressive multiple dose (PMD) protocol with and without brain temperature controlled. Three physiologic parameters were monitored and recorded from mice where brain and rectal temperatures were controlled (“Brain + Rectal”) as well as from mice where only rectal temperature controlled (“Rectal Only”). Four incremental doses of diazepam were given (post dose 1 “PD1”: 6 mg/kg; post dose 2 “PD2”: 12 mg/kg; post dose 3 “PD3”: 24 mg/kg; post dose 4 “PD4”: 48 mg/kg). Data reflect mean ± standard deviation. “Rectal only” animals were anesthetized with ketamine/xylazine whereas “Brain + Rectal” animals were anesthetized with urethane/xylazine. Brain temperatures were held at 36.0 ± 0.2 °C and rectal at 37.0 ± 0.2 °C. BPEW vehicle: 1.4 % benzyl alcohol, 38.5 % propylene glycol, 12.7 % ethyl alcohol and 48 % water. Parameters for single dose protocol (SD, 60 mg/kg) are shown below PMD data. Both brain and rectal temperatures were controlled in SD protocol. In the “Group” column, the parentheses “(N)” reflect the sample size, which remained constant over the entire study
| PMD parameters | Temperature | Groups | Baseline | PD1 (1–20 min) | PD2 (21–40 min) | PD3 (41–60 min) | PD4 (61–80 min) |
|---|---|---|---|---|---|---|---|
| SpO2 (%) | Brain + Rectal | Diazepam (10) | 86.8 ± 2.4 | 85.9 ± 1.6 | 83.7 ± 1.8 | 84.1 ± 2.5 | 83.3 ± 2.0 |
| BPEW (6) | 87.7 ± 4.8 | 88.2 ± 5.6 | 88.0 ± 4.7 | 87.3 ± 5.1 | 86.7 ± 4.9 | ||
| Rectal Only | Diazepam (10) | 86.2 ± 2.8 | 83.7 ± 3.5 | 81.7 ± 2.9 | 78.6 ± 3.7 | 76.0 ± 3.9 | |
| BPEW (10) | 85.8 ± 2.5 | 83.8 ± 3.1 | 81.6 ± 3.7 | 79.1 ± 2.9 | 78.0 ± 2.8 | ||
| Heart rate (bpm) | Brain + Rectal | Diazepam (10) | 351.6 ± 24.8 | 348.4 ± 22.2 | 325.2 ± 40.1 | 302.9 ± 62.7 | 303.3 ± 70.5 |
| BPEW (6) | 341.9 ± 13.3 | 345.6 ± 15.9 | 355.1 ± 18.0 | 357.1 ± 25.1 | 367.5 ± 20.2 | ||
| Rectal Only | Diazepam (10) | 284.8 ± 35.8 | 276.5 ± 25.9 | 267.9 ± 32.0 | 221.7 ± 39.5 | 216.7 ± 47.9 | |
| BPEW (10) | 274.3 ± 39.4 | 270.5 ± 33.3 | 266.8 ± 26.8 | 265.0 ± 24.5 | 259.5 ± 18.2 | ||
| Respiration rate (ipm) | Brain + Rectal | Diazepam (10) | 170.2 ± 7.5 | 161.5 ± 15.5 | 153.1 ± 13.8 | 145.0 ± 13.4 | 140.4 ± 13.6 |
| BPEW (6) | 184.9 ± 3.5 | 185.8 ± 3.8 | 185.8 ± 4.6 | 184.8 ± 5.0 | 184.8 ± 5.1 | ||
| Rectal Only | Diazepam (10) | 154.7 ± 4.7 | 154.6 ± 7.5 | 152.2 ± 8.2 | 150.9 ± 11.8 | 151.8 ± 11.5 | |
| BPEW (10) | 156.2 ± 17.4 | 159.1 ± 13.8 | 160.8 ± 15.1 | 162.5 ± 14.4 | 161.8 ± 13.1 |
| SD parameters | Groups | Baseline | 1–20 min | 21–40 min | 41–60 min | 61–80 min |
|---|---|---|---|---|---|---|
| SpO2 (%) | Diazepam (10) | 89.1 ± 3.0 | 88.2 ± 2.1 | 88.8 ± 2.8 | 86.1 ± 2.3 | 85.5 ± 1.9 |
| BPEW (6) | 91.8 ± 3.0 | 89.2 ± 2.9 | 86.9 ± 2.9 | 87.0 ± 5.4 | 87.0 ± 3.5 | |
| Heart rate (bpm) | Diazepam (10) | 351.5 ± 37.0 | 349.5 ± 36.6 | 353.3 ± 36.3 | 351.8 ± 37.9 | 356.8 ± 40.0 |
| BPEW (6) | 358.6 ± 41.5 | 358.4 ± 37.3 | 363.9 ± 40.5 | 367.8 ± 43.3 | 376.7 ± 58.1 | |
| Respiration rate (ipm) | Diazepam (10) | 178.3 ± 3.7 | 175.0 ± 6.7 | 167.6 ± 9.1 | 161.3 ± 9.6 | 158.3 ± 9.9 |
| BPEW (6) | 176.8 ± 5.8 | 177.3 ± 5.2 | 176.4 ± 6.8 | 176.3 ± 8.0 | 175.5 ± 9.4 |