Table 2.
Studies reporting impact of SLC polymorphisms on drug PK, PD, and outcomes in African populations
| Reference | N | Population | Substrate drug(s) | Polymorphism | Effect of polymorphism |
|---|---|---|---|---|---|
| SLC22A6 | |||||
| 7 | 92 | African (n = 24), Asian (n = 24), Caucasian (n = 24), anonymous (n = 20) | Adefovir, cidofovir, tenofovir | rs11568626 (R50H; 728G>A) | Decrease in K m for all drugs vs. wild‐type |
| R525I (8347A>T) | No change in K m for all drugs vs. wild‐type | ||||
| SLCO1B1 | |||||
| 8 | 57 | South African, black African ancestry (n = 23), mixed race (n = 34) | Rifampin | rs4149032 | Reduced bioavailability of rifampin; simulations suggested that increasing the daily rifampin dose by 150 mg in patients with the polymorphism would result in plasma concentrations similar to those of individuals with the wild‐type allele, and reduce the proportion of patients with maximum plasma concentrations (Cmax) below 8 mg/L from 63% to 31% |
| 9 | 113 | Ghanaian | Rifampin | rs2306283 (388A>G) *1b |
Potential association with rifampin PK parameters; two patients with the *1b homozygous variant (AA genotype) had significantly lower rifampin Cmax and AUC0–8 and higher CL/F and V/F than those with the wild‐type variant (GG genotype) in pairwise analysis |
| rs4149032 | No effect | ||||
| rs11045819 (463C>A)*4 | No effect | ||||
| rs4149056 (521T>C)*5 | No effect | ||||
| 10 | 57 | South African | Rifampin | rs4149032 | Low median rifampin C2.5, 3.7 μg/mL (range 2.8–5.0 μg/mL) in the heterozygous and 3.4 μg/mL (range 2.7–4.7 μg/mL) in the homozygous variant carriers; of the eight patients in whom TB recurred, seven had the polymorphism |
| 11 | 35 | South African | Rifabutin |
rs11045819 (463C>A)*4 |
Associated with a 30% increase in bioavailability of rifabutin |
| rs4149032 | No effect | ||||
| rs4149056 (521T>C)*5 | No effect | ||||
| rs2306283 (388A>G) *1b | No effect | ||||
| 12 | 86 | Bantu (black South African, n = 34; Malawians, n = 52) | Lopinavir | rs2306283 (388A>G) *1b | No effect |
| rs4149044A>T | No effect | ||||
| rs4149045G>A | No effect | ||||
| rs4149057T>C | No effect | ||||
| 13 | 30 | Zimbabwean | Rosuvastatin | rs34671512 (1929A>C) | 75% reduction in rosuvastatin exposure compared with wild‐type (P < 0.001) |
| 21 | 88 | Patients with TB: black African (n = 37), US and Spain (n = 5 black; n = 29 white; n = 1 Asian); healthy individuals from North America (n = 4 black; n = 11 white; n = 8 Hispanic) | Rifampin | rs11045819 (463C>A) | Lower rifampin exposure was associated with the polymorphism |
| 14 | 49 | Ugandan (n = 24), South African (n = 2), American (n = 23) | Moxifloxacin | rs4149015 (‐1187G>A) | AG genotype associated with significantly higher AUC0–24 and Cmax than GG genotype |
| rs59502379 (1463G>C) | No effect | ||||
| rs2306283 (388A>G) *1b | No effect | ||||
| rs11045819 (463C>A) | No effect | ||||
| rs4149056 (521T>C)*5 | No effect | ||||
| rs4149117 (334T>G) | No effect | ||||
A separate color is used to identify each polymorphism.
AUC0–8, area under the time‒concentration curve from 0 to 8 hours postdose; AUC0–24, area under the time‒concentration curve from 0 to 24 hours postdose; C2.5, concentration at 2.5 hours; Cmax, maximum plasma concentration; CL/F, apparent oral clearance; K m, affinity; PD, pharmacodynamics; PK, pharmacokinetics; SLC, solute carrier; TB, tuberculosis; V/F, apparent predicted volume of distribution.