Table 1.
Plasma and pulmonary tissue pharmacokinetic studies conducted in MTB exposed NZW rabbitsa
| Drug(s) administered (no. of animals) | Dosing regimen | Sampling times | No., type, and diam of granulomas sampled |
|---|---|---|---|
| INH, RIF, PZA, and MXF (n = 13) | All 4 drugs given once to each animal at the following doses: INH, 50 mg/kg; RIF, 30 mg/kg; PZA, 125 mg/kg; MXF, 25 mg/kg | Plasma samples at 2-4 practical times during the expt; tissue samples at euthanasia (between 0.5 and 7 h) | 46 solid granulomas, 1 to 4 mm |
| INH (n = 4) | 30 mg/kg daily for 8 days | Plasma samples at 0, 0.5-1, and 1-2 h; tissue samples at euthanasia (between 2 and 4 h) | 8 caseous, 1.5 to 3 mm; 3 suppurative, 1.5 to 3 mm |
| RIF (n = 4) | 24 mg/kg daily for 8 days | Plasma samples at 0, 0.5-1, and 1-2 h; tissue samples at euthanasia (between 1 and 3 h) | 3 solid, 1 to 4 mm; 3 caseous, 2.5 to 3 mm; 3 suppurative, 1.5 to 3 mm |
| INH, RIF, PZA, and MXF (n = 12) | All 4 drugs given to each animal once daily for 5 to 6 days: INH, 50 mg/kg; RIF, 30 mg/kg; PZA, 125 mg/kg; MXF, 25 mg/kg | Plasma samples at 2 to 4 practical times during the expt; tissue samples at euthanasia (between 1 and 17 h) | 24 solid, 1 to 4 mm; 25 caseous, 1.5 to 4 mm; 5 suppurative, 1 to 2.5 mm; 6 coalescing, >4 mm, irregular shape; 2 cavity caseous cores, ND; 3 cavity walls, ND |
a
For each study, serial plasma samples were drawn before euthanasia. Pulmonary tissue samples were obtained at study end. ND, not determined.