Table 2.
Pharmacokinetic parameters of first-line TB drugs in Tanzanian diabetic and non-diabetic TB patientsa
| Drug/pharmacokinetic parameter | TB patients with DM (n=19) | TB patients without DM (n=20) | Ratio of value for TB patients with DM versus TB patients without DM (95% CI) | P |
|---|---|---|---|---|
| Rifampicin | ||||
| AUC0–24 (mg·h/L) | 29.9 (6.4–69.7) | 39.9 (27.4–68.3) | 0.75 (0.56–1.03) | 0.052 |
| Cmax (mg/L) | 7.9 (1.9–20.7) | 8.9 (5.9–14.8) | 0.89 (0.67–1.17) | 0.384 |
| Cmax below reference range, n (%)b | 9 (47) | 7 (35) | – | 0.433 |
| Tmax (h), median (range)c | 2.1 (0.9–4.2) | 1.1 (0.9–3.0) | 0.027 | |
| t½ (h) | 1.4 (1.0–2.7) | 1.8 (1.1–3.8) | 0.80 (0.66–0.97) | 0.026 |
| Vz (L) | 38.7 (14.3–143) | 37.3 (22.7–56.5) | 1.04 (0.77–1.40) | 0.798 |
| CL (L/h) | 18.6 (8.6–70.3) | 14.4 (8.8–21.9) | 1.29 (0.98–1.71) | 0.072 |
| desacetyl-rifampicin/rifampicin ratiod | ||||
| AUC0–24 | 0.125 (0.057) | 0.133 (0.035) | – | 0.672 |
| Cmax | 0.100 (0.039) | 0.107 (0.029) | – | 0.576 |
| Isoniazid | ||||
| AUC0–24 (mg·h/L) | 5.4 (0.7–26.9) | 10.6 (3.7–22.7) | 0.51 (0.30–0.87) | 0.015 |
| Cmax (mg/L) | 1.6 (0.4–5.8) | 2.8 (1.0–4.6) | 0.60 (0.40–0.89) | 0.013 |
| Cmax below reference range, n (%)b | 14 (74) | 11 (55) | – | 0.224 |
| Tmax (h), median (range)c | 1.0 (0.9–4.1) | 1.1 (0.7–2.9) | – | 0.855 |
| t½ (h) | 2.6 (1.1–5.0) | 2.5 (1.0–4.2) | 1.03 (0.75–1.34) | 0.985 |
| Vz (L) | 189 (42.0–637) | 99 (70.2–174) | 1.90 (1.27–2.85) | 0.003 |
| CL (L/h) | 51 (8.4–410) | 27 (13.0–60.7) | 1.91 (1.09–3.32) | 0.024 |
| Pyrazinamide | ||||
| AUC0–24 (mg·h/L) | 290 (123–420) | 344 (209–609) | 0.84 (0.69–1.02) | 0.083 |
| Cmax (mg/L) | 34.5 (21.4–46.2) | 38.2 (29.0–50.8) | 0.90 (0.80–1.02) | 0.090 |
| Cmax below reference range, n (%)b | 0 | 0 | – | – |
| Tmax (h), median (range)c | 1.1 (1.0–4.0) | 1.1 (0.7–3.0) | – | 0.252 |
| t½ (h) | 5.4 (2.9–9.6) | 6.3 (4.2–15.7) | 0.85 (0.68–1.07) | 0.154 |
| Vz (L) | 39.5 (19.9–57.5) | 40.4 (29.5–98.3) | 0.98 (0.81–1.19) | 0.832 |
| CL (L/h) | 5.1 (2.9–13.0) | 4.5 (2.6–6.5) | 1.15 (0.94–1.41) | 0.170 |
| Ethambutol | ||||
| AUC0–24 (mg·h/L) | 19.6 (7.5–40.4) | 20.2 (13.4–32.0) | 0.97 (0.77–1.22) | 0.789 |
| Cmax (mg/L) | 3.1 (1.3–6.3) | 3.3 (2.2–5.8) | 0.95 (0.75–1.21) | 0.672 |
| Cmax below reference range, n (%)b | 3 (16) | 0 (0) | −e | |
| Tmax (h), median (range)c | 2.0 (1.0–4.0) | 2.0 (0.9–2.2) | – | 0.317 |
| t½ (h) | 8.6 (2.8–18.2) | 9.6 (6.9–13.5) | 0.90 (0.70–1.16) | 0.384 |
| Vz (L) | 644 (324–2533) | 719 (491–965) | 0.90 (0.69–1.17) | 0.394 |
| CL (L/h) | 51.9 (20.5–126) | 52.0 (34.3–71.3) | 1.00 (0.78–1.27) | 0.985 |
a
Data are presented as geometric mean (minimum–maximum) unless stated otherwise.
b
By Pearson’s χ2 test.
c
By Wilcoxon rank-sum test.
d
Data are presented as mean (SD). An independent-sample t-test was used for testing.
e
The requirements for the Pearson’s χ2 test were not fulfilled as the frequency of one of the two cells was not ≥1.