Pharmacokinetics of carfilzomib in patients with advanced malignancies and varying degrees of hepatic impairment: an open-label, single-arm, phase 1 study

Table 3 Inferential pharmacokinetic statistics comparing carfilzomib exposure following intravenous administration of carfilzomib (PK-evaluable population)

Sampling occasion (dose level)	PK parameters	Geometric LSM by hepatic function		Geometric mean ratios (%) 90% CIs (lower; upper)	p values
Sampling occasion (dose level)	PK parameters	Mild impairment	Normal	Geometric mean ratios (%) 90% CIs (lower; upper)	p values
27 mg/m²	AUC_0–last (ng·hr/mL)	546 (n = 14)	378 (n = 10)	144.43 (111.48; 187.12)	0.02232
27 mg/m²	AUC_0–inf (ng·hr/mL)	529 (n = 12)	348 (n = 8)	151.84 (113.59; 202.96)	0.02137

		Moderate impairment	Normal
27 mg/m²	AUC_0–last (ng·hr/mL)	477 (n = 9)	378 (n = 10)	126.08 (94.59; 168.06)	0.1812
	AUC_0–inf (ng·hr/mL)	500 (n = 7)	348 (n = 8)	143.53 (103.28; 199.45)	0.07247

		Mild impairment	Normal
56 mg/m²	AUC_0–last (ng·hr/mL)	1107 (n = 8)	765 (n = 8)	144.65 (79.2; 264.2)	0.3020
56 mg/m²	AUC_0–inf (ng·hr/mL)	1108 (n = 8)	609 (n = 6)	181.90 (96.4; 343.24)	0.1194

		Moderate impairment	Normal
56 mg/m²	AUC_0–last (ng·hr/mL)	927 (n = 5)	765 (n = 8)	121.10 (60.93; 240.67)	0.6347
56 mg/m²	AUC_0–inf (ng·hr/mL)	929 (n = 5)	609 (n = 6)	152.59 (74.87; 310.96)	0.3155

Geometric LSMs are the least squares means from ANOVA presented following back transformation to the original scale. The 90% confidence intervals are presented following back transformation to the original scale
ANOVA analysis of variance, AUC _0–last area under the concentration–time curve from time 0 to last concentration measurement, AUC _0–inf area under the concentration–time curve from time 0 extrapolated to infinity, CI confidence interval, LSM least-squares mean, PK pharmacokinetic(s)

ISSN: 2162-3619