Article Figures & Data
Figures
- Fig 1
Relationship between the acetylator status (slow versus fast/intermediate) based on two methods: the t1/2 of isoniazid and the acetyl-INH/INH metabolic ratio in the 3-h-postdose plasma sample. Patients with a t1/2 below 130 min (below the horizontal dashed line) were considered fast/intermediate metabolizers (17–19). Patients with an acetyl-INH/INH ratio greater than 0.55 (19) or greater than 1.5 (17) (right of the first or second vertical dashed line, respectively) were considered fast/intermediate metabolizers based on metabolic ratio. Note that phenotyping by t1/2 and metabolic ratio resulted in discordant results (in the upper right quadrant) in 4 patients when a metabolic ratio of 0.55 was used as the cutoff, compared to 2 patients when a metabolic ratio of 1.5 was used as the cutoff.
Tables
- Table 1
Characteristics of 20 tuberculosis patients in northern Tanzania
Characteristic Value Male sex, n (%) 15 (75) Age, median, yr (IQR) 38 (30–42) Body wt, mean, kg (SD) 55.7 (6.4) BMI, mean (SD) 19.5 (2.4) Malnutrition, n (%)a 7 (35) HIV positive, n (%) 7 (35) Type of tuberculosis, n (%) Pulmonary 19 (95) Extrapulmonary 1 (5) Concomitant drugs, n (%) Amoxicillin 1 (5) Antiretroviral treatment 2 (10) Co-trimoxazole 3 (15) Diclofenac 3 (15) Vitamin B complex 2 (10) Dose, mean, mg per kg body wt (SD) Isoniazid 5.2 (0.46) Rifampin 10.4 (0.91) Pyrazinamide 27.8 (2.4) Ethambutol 19.1 (1.7) Acetylator status, n (%,) based on: INH t1/2 Slow 12 (63) Fast/intermediate 7 (37) Acetyl-INH/INH ratio with cutoff of: 1.5 Slow 10 (53) Fast/intermediate 9 (47) 0.55 Slow 8 (42) Fast/intermediate 11 (58) ↵a Malnutrition defined as BMI of <18.5 kg/m2.
- Table 2
Pharmacokinetic parameters of tuberculosis drugs in 20 Tanzanian tuberculosis patients
Pharmacokinetic parameter Value, geometric mean (minimum-maximum) for: Isoniazida Rifampin Pyrazinamide Ethambutol AUC0–24, h · mg/liter 11 (3.7–22.7) 39.9 (27.4–68.3) 344 (209–610) 20.2 (13.4–32.0) Cmax, mg/liter 2.8 (1.0–4.6) 8.9 (5.9–14.8) 38.2 (29.0–50.8) 3.3 (2.2–5.8) Tmax, h 1.2 (0.7–2.9) 1.3 (0.9–3.0) 1.2 (0.7–3.0) 1.5 (0.9–2.2) CL/F, liters/h 25.8 (13.0–60.5) 14.4 (8.8–21.9) 4.5 (2.6–6.5) 52 (34.3–71.3) V/F, liters 99 (69.6–173.4) 37.3 (22.7–56.5) 40.3 (29.5–98.3) 719 (491–965) t1/2, h 2.9 (1.3–4.2) 1.8 (1.1–3.8) 5.5 (4.1–15.7) 9.5 (6.9–13.5) Reference range Cmax, mg/liter 3–5 8–24 20–50 2–6 No. (%) with Cmax below reference range 10 (52) 7 (35) 0 (0) 0 (0) ↵a Isoniazid plasma concentrations were determined for only 19 patients.
