Table 1.
Summary of dosing strategies and PK properties pertaining to metabolism and transport‐mediated DDI potential for WHO‐recommended treatments for TB infection
| Drug | Dose and range (mg/kg body weight)13 | Dosing order/duration | Primary elimination route | In vivo metabolism/transporta | ||
|---|---|---|---|---|---|---|
| Substrate | Inhibitor | Inducer | ||||
| Ethambutol | 15 (15–20) | 1st, 2 months | Renal | — | — | Not available |
| Isoniazid | 5 (4–6) |
1st, 2 months 2nd, 4 months |
Renal | NAT2 | CYPs 3A4, 2C19, 2E1, 1A2 | CYP2E1 |
| Pyrazinamide | 25 (20–30) | 1st, 2 months | Renal | Pyrazinamidase | — | Not available |
| Rifampicin | 10 (8–12) |
1st, 2 months 2nd, 4 months |
Biliary |
Arylacetamide deacetylase OATP1B1/1B3, P‐gp |
OATP1B/3, P‐gp |
CYPs 3A, 2B6, 2C9, 2C19, 2C8, 1A2 P‐gp |
CYP, cytochrome P450; DDI, drug–drug interaction; NAT2, N ‐acetyltransferase 2; OATP, organic anion transporting peptide; P‐gp, P‐glycoprotein; PK, pharmacokinetic; TB, tuberculosis; WHO, World Health Organization.
a
Listed from most to least sensitive substrate (Michaelis constant (K m)), potent inhibitor (inhibitor constant (K i) or half‐maximal inhibitory concentration (IC50)), or inducer (fold‐increase enzyme activity).