TABLE 3.
Rifampin pharmacokinetic parameter by SLCO1B1 and CES2 single nucleotide polymorphism status in 113 Ghanaian children with TBa
| Genetic factor (%) | Cmax (μg/ml) | AUC0–8h (μg · h/ml) | CL/F (liters/h) | V/F (liters) |
|---|---|---|---|---|
| SLCO1B1c.388A>G (*1b) | ||||
| AA (1.8) | 1.81 (0.81–2.80) | 9.33 (2.35–16.31) | 44.54 (15.38–73.69) | 109.23 (54.86–163.59) |
| AG (30.1) | 5.86 (4.71–8.72) | 26.84 (20.90–34.71) | 7.38 (5.22–10.37) | 20.73 (15.64–32.76) |
| GG (68.1) | 7.11 (5.08–8.79) | 29.50 (20.79–38.71) | 7.43 (4.86–10.06) | 21.98 (14.20–30.12) |
| P value | 0.052 | 0.085 | 0.093 | 0.067 |
| SLCO1B1c.388A>G (*1b) | ||||
| AA/AG (31.9) | 5.84 (4.08–8.34) | 26.35 (16.67–34.27) | 7.58 (5.26–12.73) | 22.07 (15.95–40.54) |
| GG (68.1) | 7.11 (5.08–8.79) | 29.50 (20.79–38.71) | 7.43 (4.86–10.06) | 21.98 (14.20–30.12) |
| P value | 0.147 | 0.181 | 0.583 | 0.265 |
| SLCO1B1 rs4149032 (intron SNP) | ||||
| CC (57.5) | 7.00 (5.10–8.77) | 29.50 (21.23–36.58) | 7.34 (4.99–9.79) | 21.20 (13.46–31.00) |
| CT (31.9) | 6.55 (4.59–8.81) | 26.35 (16.74–37.82) | 7.58 (4.62–11.56) | 21.80 (16.64–30.48) |
| TT (10.6) | 5.43 (3.25–6.90) | 24.07 (13.58–29.58) | 8.37 (5.88–14.74) | 23.59 (13.02–49.79) |
| P value | 0.228 | 0.262 | 0.462 | 0.657 |
| SLCO1B1 c.463C>A (*4) | ||||
| CC (84.1) | 6.50 (4.94–8.79) | 27.25 (20.37–37.46) | 7.52 (4.63–10.67) | 22.13 (14.72–32.10) |
| CA (15.0) | 5.70 (4.28–7.96) | 27.67 (23.05–30.06) | 7.18 (5.78–9.10) | 17.72 (13.16–28.79) |
| AA (0.09) | 1.72 (1.72, 1.72) | 9.35 (9.35, 9.35) | 14.81 (14.81, 14.81) | 63.01 (63.01, 63.01) |
| P value | 0.262 | 0.304 | 0.422 | 0.248 |
| SLCO1B1 c.463C>A (*4) | ||||
| CC (84.1) | 6.50 (4.94–8.79) | 27.25 (20.37–37.46) | 7.52 (4.63–10.67) | 22.13 (14.72–32.10) |
| CA/AA (15.9) | 5.68 (4.02–7.96) | 27.30 (21.11–30.06) | 7.26 (5.78–9.79) | 18.46 (13.16–28.95) |
| P value | 0.417 | 0.621 | 0.919 | 0.701 |
| SLCO1B1 c.521T>C (*5) | ||||
| TT (97.3) | 6.32 (4.92–8.79) | 27.08 (20.62–36.58) | 7.49 (4.86–10.37) | 21.59 (14.72–31.00) |
| TC (2.7) | 8.05 (3.23–8.68) | 29.83 (16.44–35.30) | 5.10 (4.99–12.50) | 49.09 (7.82–58.79) |
| P value | 0.986 | 0.915 | 0.761 | 0.464 |
| CES2 c.–2263A>G | ||||
| AA (49.6) | 7.17 (4.94–8.81) | 29.00 (20.95–38.31) | 7.41 (5.04–9.69) | 19.89 (14.02–30.56) |
| AG (41.6) | 5.85 (3.69–8.17) | 24.48 (16.31–34.71) | 7.71 (5.57–12.50) | 23.36 (15.64–36.76) |
| GG (8.8) | 6.90 (5.90–9.24) | 30.62 (25.12–43.45) | 4.48 (2.25–9.80) | 21.80 (10.17–27.42) |
| P value | 0.134 | 0.179 | 0.207 | 0.487 |
a
PK parameter values are medians (IQR). Tmax, time to maximum concentration; Cmax, maximum concentration; AUC0–8h, area under the time-concentration curve from time 0 to 8 h postdose; CL/F, apparent oral clearance; V/F, apparent predicted volume of distribution.