Table 4.
Summary of pharmacokinetic parameters for olanzapine and samidorphan in subjects with severe renal impairment and healthy control subjects after a single oral dose of OLZ/SAM (5 mg olanzapine/10 mg samidorphan)
| Parameter, arithmetic mean (SD) | Olanzapine | Samidorphan | ||
|---|---|---|---|---|
| Severe renal impairment (N=10) | Healthy control (N=10) | Severe renal impairment (N=10) | Healthy control (N=10) | |
| Cmax (ng/mL) | 7.36 (3.62) | 5.25 (1.59) | 34.58 (9.43) | 26.09 (6.45) |
| tmax (hr)a | 5.1 (3.0–7.0) | 4.5 (2.0–12.0) | 1.5 (0.5–4.0) | 1.0 (0.5–4.0) |
| t1/2 (hr) | 57.8 (15.0) | 45.6 (11.9) | 17.1 (4.7) | 11.4 (2.8) |
| AUClast (hr×ng/mL) | 347 (127) | 228 (58) | 519 (110) | 224 (42) |
| AUC0-∞ (hr×ng/mL) | 404 (138) | 256 (68) | 530 (109) | 233 (43) |
| CL/F (L/hr) | 13.9 (5.9) | 20.7 (4.9) | 19.7 (4.4) | 44.6 (10.2) |
| Vz/F (L) | 1122 (405) | 1306 (258) | 468 (104) | 706 (101) |
| CLR(L/hr) | 0.964 (0.812) | 1.93 (1.43) | 1.92 (0.69) | 9.87 (2.62) |
Note: aMedian (min, max) presented for tmax.
Abbreviations: Ae0-168, total amount of drug excreted from 0 to 168 hrs after dosing; AUClast, area under the plasma concentration-time curve from time 0 to last observed concentration above the lower limit of quantification; AUC0-∞, area under the plasma concentration-time curve from time 0 to infinity; CL/F, apparent clearance; CLR, renal clearance; Cmax, maximum observed concentration; OLZ/SAM, olanzapine/samidorphan; SD, standard deviation; tmax, time to maximum observed concentration; t½, terminal elimination half-life; Vz/F, apparent volume of distribution.