Table 1. Pharmacokinetic characteristics of anti-tuberculosis drugs.
| Drug | Usual dose | Serum Cmax (µg/mL) | Serum Tmax (hr) | Serum T½ (hr) | CSF Penetration (%) | Protein Binding (%) | VD (L/kg) | Renal exc. (%) | Hepatic clearance (%) | Active metab. | Metab. exc. (%) | Dose renal failure | Dose hepatic dis. |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Isoniazid | 300 mg daily | 3–6 | 0.75–2 | Polymorphic | 20–100 | 10 est. | 0.6–1 est. | Polymorphic | Polymorphic | None | Renal (50–60) and nonrenal | Unchanged or reduced to every other day | Unchanged in most patients |
| 900 mg biw | 9–15 | fast: 1.5; slow: 4 | fast: 10, slow: 30 | fast: 90, slow: 70 | |||||||||
| Rifampin | 600 mg daily | 8–24 | 2 | 2–3 | 5–20 est. Variable | 60–80 est. | 0.6–1 est. | 10 | 90 | Yes: deacetyl | Renal (20) and nonrenal | Unchanged in most patients | Unchanged in most patients |
| Rifabutin | 300 mg daily | 0.45–0.90 | 3–4 | 25–36 | 30–70 | 70–90 | 8–9 | 10 | 90 | Yes: 25-O- deacetyl | Renal (35) and nonrenal | Unchanged in most patients | Unchanged in most patients |
| Rifapentine | 600 mg daily* | 8–30 | 5 | 15 | |||||||||
| Pyrazinamide | 25–35 mg/kg daily | 20–60 | 1–2 | 9 | 50–100 | Not known | 0.6–0.7 est. | 5 | 95 | None | Renal | 15–30 mg/kg 3×weekly |
Not known |
| 50 mg/kg biw | 60–90 | ||||||||||||
| Ethambutol | 25 mg/kg daily | 2–6 | 2–3 | Biphasic: 2–4, then 12–14 | 5–65 est. Variable | 6–30 est. | 1.6–3.8 | 80 | 20 | None | None | 15–25 mg/kg 3×weekly |
Unchanged |
| 50 mg/kg biw | 4–12 | ||||||||||||
| Cycloserine | 250–500 mg daily or biw | 20–35 | 2 | 7 | 50–80 | Not known | 0.2–0.35 est. | 70–100 | Not known | Not known | Not known | 250–500 mg 3×weekly |
Unchanged |
| Ethionamide | 250–500 mg daily or biw | 2–5 | 2 | 2 | 20–100 est. | Not known, 30 est. | 1.5–4 est. | 5 | 95 | Yes: sulfoxide | Nonrenal | Unchanged | Not known |
| Streptomycin/kanamycin/amikacin | 15 mg/kg daily | 35–45† | 0.5–1.5 IM dose or calculated to the end of IV infusion | 3 | 20–40 est. | 0–60 est. | 0.2–0.3 | >95 | 0 | None | None | 12–15 mg/kg 3×weekly |
Unchanged |
| 25 mg/kg biw | 65–80† | ||||||||||||
| PAS granules | 4,000 mg bid | 20–60 | 4–8 | 1 | 10–50 | 50–73 (15 in some reports) | 0.8–3.8 est. | 10 | 90 | None | Renal | Unknown: avoid if possible | Not known |
| Levofloxacin | 500–1,000 mg daily | 8–13 | 1–2 | 9 | 60–80 | 24–38 | 1.27 | <92 | Minimal | None | Renal | 250–1,000 mg 3×weekly |
Unchanged in most patients |
| Moxifloxacin | 400 mg daily | 3–5 | 1–2 | 7 | 70–80 | 30–50 | 1.7–2.7 | 20 | 25 | None | Renal (<5) and nonrenal | Unchanged | Unchanged in mild impairment |
| Linezolid | 600–300 mg 1–2 times daily |
12–26 | 1.5 | 5–6 | 80–100 | 31 | 0.45–0.67 | 30 | 60 | None | Renal (50) and nonrenal | Unchanged | Unchanged in mild impairment |
| Clofazimine | 100 mg daily | 0.5–2.0 | 2–7 | Biphasic: several days, then many weeks | Not known | Not known | Not known | <1 | Yes (% unknown) | None | Nonrenal | Unchanged | Unchanged |
Information in the table is from the following references [16,61,62].
*The US FDA approved dose is two times weekly in the initial phase and once weekly in the continuation phase for selected patients [16]; †Calculated Cmax to 1 hr post-IM dose or end of IV infusion (using linear regression).
Abbreviations: metab., metabolite; VD, volume of distribution; bid, twice daily; biw, twice weekly; Cmax, peak serum concentration; CSF, cerebrospinal fluid; est., estimated; exc., excretion; IM, intramuscular; IV, intravenous; PAS, para-aminosalicylic acid; Tmax, the time at which Cmax occurs; T½, half-life.