Table I.
Study Design
| Protocol | Animals | Route, dose (injection volume) | Formulation | Sampling time points | |||
|---|---|---|---|---|---|---|---|
| Knee | Tissuesa | Urine | Blood, plasma, or serum | ||||
| Study 1 | Naïve female rats (n = 3 per time point) | IA, 20 μg (70 μL) per knee | PBS | 5 min–28 h | NC | NC | NC |
| Study 2 | Naïve female rats (n = 5 per time point) | IA, 20 μg (40 μL) per knee | PBS | 24–672 h | NC | NC | 10 min–672 h (serum) |
| Study 3 | Naïve male rats (n = 5) per time point | IA, 20 μg (40 μL) per knee | Arg Buffer | 6–504 h | 6 and 24 h | 24, 48, 72 h | 6–168 h (plasma) |
| Study 4 | Naïve and MT male rats (n = 5 per time point per group) | IA, 8.3 μg (40 μL) per knee | PBS | 24 and 168 h | NC | NC | 5 min–48 h (blood and plasma) |
| Study 5 | Naïve male rats (n = 5, serial sampling) | IV, 0.5 mg/kg (1 mL/kg) | Arg Buffer | NC | NC | 24, 48, 72 h | 2 min–72 h (plasma) |
Lewis rats were used for all studies
MT meniscal tear surgery, Arg Buffer 0.2 M arginine, 10 mM Citrate, PBS phosphate-buffered saline, NC not collected
aTissues were liver, kidney, and spleen