Table 3.
Levonorgestrel (LNG), Efavirenz (EFV) and Nevirapine (NVP) pharmacokinetic parameters shown as median (interquartile range), summarized by associated CYP2B6, NR1I2 or CYP2A6 genotype.
| LNG Cmax (pg/mL) | CYP2B6 516G>T (rs3745274) | CYP2B6 15582C>T (rs4803419) | CYP2A6*9B 1836G>T (rs8192726) | NR1I2 63396C>T (rs2472677) | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| GG | GT | TT | CC | CT | TT | GG | GT | TT | CC | CT | TT | |
| EFV group | 692.57 (486.82–887.95) | 402.40 (223.07–1027.65) | 200.63 | 692.57 (501.09–706.56) | 486.82 (347.10–775.28) | - | 486.82 (359.66–706.56) | 585.19 (223.07–1405.43) | - | 486.82 (347.10–775.28) | 463.03 (419.79–1027.65) | 585.19 |
| NVP group | 1310.78 (1069.99–2530.06) | 1449.53 (1053.42–1836.94) | - | 1097.94 (814.90–2157.00) | 1449.53 (1069.99–1836.94) | 1267.16 | 1449.53 (1267.16–1836.94) | 1097.94 (1069.99–1543.09) | - | 1436.43 (1054.42–1877.35) | 1310.78 (1303.20–1818.52) | 1466.49 (775.98–2157.00) |
| LNG Tmax (wk) | ||||||||||||
| EFV group | 1.00 (1.00–1.00) | 1.00 (1.00–1.00) | 4.00 | 1.00 (1.00–1.00) | 1.00 (1.00–12.00) | - | 1.00 (1.00–4.00) | 1.00 (1.00–36.00) | - | 1.00 (1.00–12.00) | 1.00 (1.00–1.00) | 1.00 |
| NVP group | 1.00 (1.00–1.00) | 1.00 (1.00–12.00) | - | 1.00 (1.00–1.00) | 1.00 (1.00–1.00) | 1.00 | 1.00 (1.00–1.00) | 1.00 (1.00–1.00) | - | 1.00 (1.00–1.00) | 1.00 (1.00–1.00) | 6.50 (1.00–12.00) |
| LNG Cmin (pg/mL) | ||||||||||||
| EFV group | 272.21 (189.45–377.85) | 202.23 (175.86–359.66) | 121.82 | 298.99 (272.98–307.27) | 208.13 (188.23–274.21) | - | 224.66 (188.23–307.27) | 202.23 (189.45–1405.43) | - | 223.07 (188.23–359.66) | 202.23 (189.13–298.99) | 189.45 |
| NVP group | 553.65 (365.16–1094.09) | 562.62 (504.42–807.67) | - | 504.42 (343.67–713.96) | 562.38 (512.46–986.40) | 526.38 | 562.38 (504.42–807.67) | 724.96 (540.18–986.40) | - | 540.18 (501.00–956.95) | 562.62 (562.38–986.40) | 599.33 (512.46–686.21) |
| LNG AUC0–24weeks (pg*wk/mL) | ||||||||||||
| EFV group | 10114.61 (8069.30–12862.18) | 6311.80 (6569.71–14937.71) | 3622.06 | 10114.61 (8499.98–12798.81) | 7754.35 (5676.92–9435.56) | - | 7754.35 (6311.80–11399.63) | 8069.30 (4321.25–11070.02) | - | 6830.55 (5676.92–11399.63) | 7754.35 (7371.57–10114.61) | 8069.30 |
| NVP group | 19970.24 (15259.29–30339.86) | 15965.35 (15729.55–26301.13) | - | 15761.90 (11338.65–22478.35) | 20167.18 (15729.55–27442.02) | 19970.24 | 19970.24 (15761.90–26301.13) | 16948.72 (15258.29–21199.91) | - | 16948.72 (15729.55–26301.13) | 16759.11 (15258.29–27442.02) | 19189.39 (15900.44–22478.35) |
| EFV C12–14h (mg/L) | 2.06 (1.39–2.61) | 2.63 (2.05–6.89) | 8.71 | 2.38 (2.20–2.63) | 2.35 (1.75–5.06) | - | 2.38 (1.75–3.03) | 2.35 (1.99–6.64) | - | 2.61 (2.05–6.64) | 2.21 (2.01–2.38) | 1.62 |
| NVP C11–13h (mg/L) | 6.51 (4.40–7.36) | 6.16 (5.10–10.03) | - | 6.75 (5.85–8.33) | 6.10 (4.95–8.34) | 8.01 | 6.10 (5.10–8.42) | 6.63 (5.45–7.14) | - | 6.75 (4.81–8.42) | 6.16 (5.50–6.86) | 7.06 (5.85–8.27) |
EFV C12–14h (mg/L) and NVP C11–13h (mg/L) determined from individual participant’s geometric mean value calculated from concentration measured at study entry, week 1, 4, 12, 24, 36 and 48 and summarized for the group as median (interquartile range).