Table 3.
Multiple‐ascending dose assessment: descriptive summary of plasma and urine nirmatrelvir pharmacokinetic parameters
| Parameter (unit)a |
Nirmatrelvir/r 75/100 mg b.i.d. Fasted (N = 4) |
Nirmatrelvir/r 250/100 mg b.i.d. Fasted (N = 4) |
Nirmatrelvir/r 500/100 mg b.i.d. Fasted (N = 7) |
Nirmatrelvir/r 250/100 mg b.i.d. Fasted, Japanese (N = 4) |
|---|---|---|---|---|
| Day 1 | ||||
| N1a | 4 | 4 | 7 | 4 |
| AUCtau, ng hour/mL | 6,017 (33) | 18,700 (43) | 22,610 (37) | 13,130 (26) |
| Cmax, ng/mL | 1,042 (28) | 2,435 (36) | 3,051 (32) | 1,925 (25) |
| Tmax, hours | 1.75 (1.00–2.00) | 1.50 (1.00–4.00) | 2.00 (1.50–2.17) | 2.75 (1.00–4.02) |
| Day 5 | ||||
| N1a | 4 | 4 | 7 | 4 |
| AUCtau, ng hour/mL | 12,570 (17) | 35,560 (26) | 38,150 (23) | 25,480 (26) |
| Cmax, ng/mL | 2,224 (27) | 4,774 (21) | 5,296 (21) | 3,674 (28) |
| Rac | 2.091 (24) | 1.901 (22) | 1.685 (29) | 1.937 (18) |
| Tmax, hours | 1.00 (1.00–1.50) | 0.750 (0.500–1.50) | 1.50 (1.00–2.02) | 1.26 (1.00–2.02) |
| Day 10 | ||||
| N1, N2a | 4, 4 | 4, 4 | 7, 7 | 4, 4 |
| AUCtau, ng hour/mL | 12,650 (16) | 37,780 (27) | 39,780 (20) | 26,930 (15) |
| Cmax, ng/mL | 2,055 (14) | 5,123 (24) | 5,607 (17) | 3,772 (21) |
| Rac | 2.104 (30) | 2.022 (16) | 1.757 (26) | 2.047 (16) |
| t ½, hours | 7.955 ± 2.0401 | 6.795 ± 1.7072 | 8.047 ± 1.7871 | 5.163 ± 2.0915 |
| Tmax, hours | 1.00 (1.00–2.00) | 1.00 (1.00–2.00) | 1.50 (1.00–2.00) | 1.50 (0.500–2.02) |
| Aetau % | 63.79 (12) | 51.81 (4) | 23.35 (121) | 54.20 (5) |
| CLr, L/hour | 3.782 (20) | 3.433 (23) | 2.934 (128) | 5.028 (11) |
Results are for pharmacokinetic parameter set (defined in Table S2 ) and show the geometric mean (geometric %CV) for all except for Tmax, which is the median (range) and t 1/2 which is the arithmetic mean ± SD. For the parameters analyzed on the log scale, zero values were substituted with 0.0001 prior to log transformation. The parameters are defined in Table S1 . Additional results are in Table S6 .
%CV, percent coefficient of variation; AUCtau, area under the concentration curve for a dosing interval; b.i.d., twice daily; CLr, renal clearance; Cmax, maximum plasma concentration; r, ritonavir; t 1/2, terminal half‐life; Tmax, time to maximum plasma concentration.
aN1 is the number of participants contributing to the summary statistics and N2 is the number of participants where t 1/2 was determined.