Table 2.
Summary of 7-Hydroxy Methotrexate (7-OH MTX) Plasma Pharmacokinetic Parameters of after administration of methotrexate alone (i.e. Day 1) and methotrexate after co-administration with Apremilast (i.e., Day 8)
| Treatment | Arithmetic Mean (Standard Deviation)a | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| tmaxb (hr) | Cmax (ng/mL) | AUC0–t (hr ng/mL) | AUC0–∞ (hr ng/mL) | t1/2 (hr) | ||||||
| 7-OH MTX | 7-OH MTX + Apremilast | 7-OH MTX | 7-OH MTX + Apremilast | 7-OH MTX | 7-OH MTX + Apremilast | 7-OH MTX | 7-OH MTX + Apremilast | 7-OH MTX | 7-OH MTX + Apremilast | |
| MTX 10 mg (N = 1) | 5.98 | 6.00 | 21.0 | 32.9 | 430 | 620 | 460 | 650 | 11.9 | 10.9 |
| N = 1 | N = 1 | N = 1 | N = 1 | N = 1 | N = 1 | N = 1 | N = 1 | N = 1 | N = 1 | |
| MTX 12.5 mg (N = 1) | 6.00 | 6.00 | 52.8 | 72.8 | 1,220 | 1,670 | 1,370 | 1,820 | 14.2 | 12.0 |
| N = 1 | N = 1 | N = 1 | N = 1 | N = 1 | N = 1 | N = 1 | N = 1 | N = 1 | N = 1 | |
| MTX 15 mg (N = 6) | 7.52 (6.00–12.00) | 8.99 (6.00–9.07) | 64.7 (34.4) | 66.1 (29.0) | 1,330 (605.3) | 1,280 (490.1) | 1,470 (701.5) | 1,370 (506.4) | 12.0 (1.76) | 11.4 (1.86) |
| N = 6 | N = 6 | N = 6 | N = 6 | N = 6 | N = 6 | N = 6 | N = 6 | N = 6 | N = 6 | |
| MTX 17.5 mg (N = 1) | 6.00 | 9.00 | 45.4 | 48.9 | 1,170 | 1,170 | 1,300 | 1,290 | 13.0 | 12.2 |
| N = 1 | N = 1 | N = 1 | N = 1 | N = 1 | N = 1 | N = 1 | N = 1 | N = 1 | N = 1 | |
| MTX 20 mg (N = 6) | 7.54 (5.95–9.00) | 6.09 (5.97–9.00) | 83.3 (20.0) | 76.5 (22.4) | 1,800 (461.6) | 1,650 (630.5) | 1,980 (580.1) | 1,870 (834.5) | 12.0 (2.45) | 13.1 (4.08) |
| N = 6 | N = 6 | N = 6 | N = 6 | N = 6 | N = 6 | N = 6 | N = 6 | N = 6 | N = 6 | |
| Ratio of geometric means | 0.005c | 104.01 | 98.59 | 98.24 | NC | |||||
| 90% CI of ratio of geometric means | (−1.405, 1.45)d | (92.82, 116.55) | (86.86, 111.91) | (86.85, 111.13) | NC | |||||
| Intra-subject CV% | 0.9902e | 17.84 | 19.89 | 19.34 | NC | |||||
| N = 15 | N = 15 | N = 15 | N = 15 | NC | ||||||
N, number of subjects; CV, coefficient of variation; Cmax, maximum observed plasma concentration; tmax, time to maximum plasma concentration; t1/2, estimate of the terminal elimination half-life in plasma; AUC0–t, area under the plasma concentration-time curve from time 0 to the last quantifiable concentration; AUC0–∞, area under the plasma concentration-time curve from time 0 extrapolated to infinity; CL/F, apparent total plasma clearance when dosed orally; Vz/F, apparent total volume of distribution when dosed orally; NA, not applicable.
Arithmetic mean when appropriate (i.e., N > 1).
tmax is summarized by median and range (minimum to maximum), when appropriate.
median difference (“MTX + Apremilast” − “MTX”).
90% CI of the median difference are from Hodges–Lehmann Estimate.
P-value is from Wilcoxon signed-rank test.