Table 3. EFV pharmacokinetic parameters in plasma and breast milk and breastfed infants’ exposure.
| Pooled | CYP2B6 516GG | CYP2B6 516GT | CYP2B6 516TT | |
| Preliminary phase pharmacokinetic data | n = 117 | n = 42 | n = 52 | n = 23 |
| Maternal plasma EFV conc. (ng/mL) | 2310 (632-8880) | 1660 (632-3610) | 2390 (951-8880) | 5400 (1920-8110) |
| Breast milk EFV conc. (ng/mL) | 2280 (475-10800) | 1610 (475-5580) | 2370 (713-10300) | 4070 (995-10800) |
| Infant plasma EFV conc. (ng/mL) | 173 (46.0-4630) | 124 (46.0-4630) | 164 (48.5-2150) | 333 (75.5-1590) |
| Intensive pharmacokinetic parameters | n = 29 | n = 10 | n = 11 | n = 8 |
| Plasma | ||||
| Cl/F (L/h)a | 9.89 (3.39-22.4) | 12.2 (9.37-22.4) | 10.0 (4.71-20.7) | 4.64 (3.39-5.35) |
| AUC0-24 (ng.h/mL)a | 60700 (26800-177000) | 49400 (26800-64000) | 59700 (29000-128000) | 130000 (112000-177000) |
| Cmax (ng/mL)a | 4630 (2050-9760) | 3220 (2310-4630) | 4750 (2050-6780) | 6940 (5560-9760) |
| Cmin (ng/mL)a | 2030 (755-6740) | 1640 (861-2310) | 1580 (755-4860) | 5150 (3830-6740) |
| Breast milk | ||||
| AUC0-24 (ng.h/mL)b | 68500 (26300-257000) | 55000 (29200-105000) | 60600 (26300-206000) | 105000 (68100-257000) |
| Cmax (ng/mL)c | 5390 (1430-18400) | 4020 (2400-8450) | 4540 (1430-9220) | 8920 (5810-18400) |
| Cmin (ng/mL)d | 1680 (316-9570) | 1120 (534-2430) | 1500 (316-6070) | 2480 (1500-9570) |
| Time averaged M/P conc. ratio | 1.10 (0.57-1.71) | 1.22 (0.61-1.71) | 1.08 (0.57-1.57) | 0.98 (0.59-1.66) |
| M/P AUC0-24 ratio | 1.13 (0.50-1.93) | 1.23 (0.71-1.93) | 1.18 (0.73-1.73) | 0.95 (0.57-1.66) |
| Infant exposure | ||||
| Average infant EFV dose (µg/kg/day) | 428 (164-1610) | 344 (182-656) | 379 (164-1290) | 656 (426-1610) |
| Maximum infant EFV dose (µg/kg/day) | 809 (215-2760) | 603 (360-1270) | 681 (215-1380) | 1340 (872-2760) |
| Average EIpaediatrice (%) | 2.14 (0.82-8.05) | 1.72 (0.91-3.28) | 1.90 (0.82-6.45) | 3.28 (2.13-8.05) |
| Maximum EIpaediatrice (%) | 4.05 (1.08-13.8) | 3.02 (1.80-6.35) | 3.41 (1.08-6.90) | 6.70 (4.36-13.8) |
| EImaternale (%) | 7.69 (2.04-26.2) | 5.73 (3.42-12.1) | 6.47 (2.04-13.1) | 12.7 (8.28-26.2) |
| Infant plasma EFV conc. 1f(ng/mL) | 173 (27.2-1590) | 166.10 (27.3-208) | 88.53 (37.7-273) | 293 (103-1590) |
| Infant plasma EFV conc. 2f (ng/mL) | 146 (29.9-1130) | 133.54 (30.0-223) | 85.83 (45.2-313) | 342 (113-1130) |
Values are presented as median (range).
a, b and c: Significant differences between genotype groups (Kruskal-Wallis test) at 0.001, 0.05, 0.01 and levels, respectively
d
no significant difference between genotype groups (Kruskal-Wallis test)
e
EIpaediatric and EImaternal represent paediatric and maternal dose weight-adjusted exposure indices, respectively (average EIpaediatric was calculated by replacing InfantDosemax with InfantDoseavg in equation 3)
f
Infant plasma EFV conc. 1 and 2 represent infant plasma concentrations 2 h and 8 h after maternal dose, respectively.