Details der Publikation - Population pharmacokinetics of siltuximab: impact of disease state

Population pharmacokinetics of siltuximab: impact of disease state

Purpose To characterize the effects of disease type and clinical characteristics on the pharmacokinetics of siltuximab, an IL-6 inhibiting monoclonal antibody. Methods Siltuximab pharmacokinetic data were combined from seven phase I/II clinical trials. A population pharmacokinetic model was developed to characterize changes in siltuximab disposition with disease type, albumin, liver and renal function, and patient demographics. Results A total of 7761 concentrations from 460 participants were used in the study. The data were well described by a two-compartment model. Castleman’s disease, healthy volunteer status, albumin, and ALT were independent predictors of clearance. Monte Carlo simulations of the final model for an 11 mg/kg dose resulted in a longer median half-life for healthy volunteers (24.5 days) as compared to Castleman’s disease (19.1 days) and other tumor types (22.2 days). Clearance varied 1.8-fold over the range of albumin values seen in the study (1.5–5.2 g/dL), while ALT resulted in minimal changes in clearance. Conclusions Albumin and disease state are important factors for siltuximab disposition and will likely need to be considered for dosing in future therapeutic applications..

Medienart:	E-Artikel

Erscheinungsjahr:	2019
Erschienen:	2019

Enthalten in:	Zur Gesamtaufnahme - volume:84
Enthalten in:	Cancer chemotherapy and pharmacology - 84(2019), 5 vom: 03. Sept., Seite 993-1001

Sprache:	Englisch

Beteiligte Personen:	Nikanjam, Mina [VerfasserIn] Yang, Jin [VerfasserIn] Capparelli, Edmund V. [VerfasserIn]

Links:	Volltext [lizenzpflichtig]

Themen:	Castleman’s disease IL-6 Oncology Population pharmacokinetics Siltuximab

RVK:	RVK Klassifikation ELIB24

Anmerkungen:	© Springer-Verlag GmbH Germany, part of Springer Nature 2019

doi:	10.1007/s00280-019-03939-7

funding:
Förderinstitution / Projekttitel:

PPN (Katalog-ID):	OLC2091768340

Internformat


LEADER	01000naa a22002652 4500
001	OLC2091768340
003	DE-627
005	20230331071256.0
007	cr uuu---uuuuu
008	230331s2019 xx \|\|\|\|\|o 00\| \|\|eng c
024	7		\|a 10.1007/s00280-019-03939-7 \|2 doi
035			\|a (DE-627)OLC2091768340
035			\|a (DE-He213)s00280-019-03939-7-e
040			\|a DE-627 \|b ger \|c DE-627 \|e rakwb
041			\|a eng
082	0	4	\|a 610 \|q VZ
084			\|a PHARM \|q DE-84 \|2 fid
084			\|a ELIB24 \|q VZ \|2 rvk
100	1		\|a Nikanjam, Mina \|e verfasserin \|0 (orcid)0000-0001-7052-6348 \|4 aut
245	1	0	\|a Population pharmacokinetics of siltuximab: impact of disease state
264		1	\|c 2019
336			\|a Text \|b txt \|2 rdacontent
337			\|a Computermedien \|b c \|2 rdamedia
338			\|a Online-Ressource \|b cr \|2 rdacarrier
500			\|a © Springer-Verlag GmbH Germany, part of Springer Nature 2019
520			\|a Purpose To characterize the effects of disease type and clinical characteristics on the pharmacokinetics of siltuximab, an IL-6 inhibiting monoclonal antibody. Methods Siltuximab pharmacokinetic data were combined from seven phase I/II clinical trials. A population pharmacokinetic model was developed to characterize changes in siltuximab disposition with disease type, albumin, liver and renal function, and patient demographics. Results A total of 7761 concentrations from 460 participants were used in the study. The data were well described by a two-compartment model. Castleman’s disease, healthy volunteer status, albumin, and ALT were independent predictors of clearance. Monte Carlo simulations of the final model for an 11 mg/kg dose resulted in a longer median half-life for healthy volunteers (24.5 days) as compared to Castleman’s disease (19.1 days) and other tumor types (22.2 days). Clearance varied 1.8-fold over the range of albumin values seen in the study (1.5–5.2 g/dL), while ALT resulted in minimal changes in clearance. Conclusions Albumin and disease state are important factors for siltuximab disposition and will likely need to be considered for dosing in future therapeutic applications.
650		4	\|a Siltuximab
650		4	\|a IL-6
650		4	\|a Population pharmacokinetics
650		4	\|a Oncology
650		4	\|a Castleman’s disease
700	1		\|a Yang, Jin \|4 aut
700	1		\|a Capparelli, Edmund V. \|4 aut
773	0	8	\|i Enthalten in \|t Cancer chemotherapy and pharmacology \|d Springer Berlin Heidelberg, 1978 \|g 84(2019), 5 vom: 03. Sept., Seite 993-1001 \|h Online-Ressource \|w (DE-627)253390435 \|w (DE-600)1458488-8 \|w (DE-576)072283467 \|x 1432-0843 \|7 nnns
773	1	8	\|g volume:84 \|g year:2019 \|g number:5 \|g day:03 \|g month:09 \|g pages:993-1001
856	4	0	\|u https://dx.doi.org/10.1007/s00280-019-03939-7 \|z lizenzpflichtig \|3 Volltext
912			\|a GBV_USEFLAG_A
912			\|a SYSFLAG_A
912			\|a GBV_OLC
912			\|a FID-PHARM
912			\|a SSG-OPC-PHA
912			\|a GBV_ILN_11
912			\|a GBV_ILN_20
912			\|a GBV_ILN_22
912			\|a GBV_ILN_23
912			\|a GBV_ILN_31
912			\|a GBV_ILN_32
912			\|a GBV_ILN_39
912			\|a GBV_ILN_40
912			\|a GBV_ILN_60
912			\|a GBV_ILN_62
912			\|a GBV_ILN_63
912			\|a GBV_ILN_69
912			\|a GBV_ILN_70
912			\|a GBV_ILN_73
912			\|a GBV_ILN_74
912			\|a GBV_ILN_90
912			\|a GBV_ILN_95
912			\|a GBV_ILN_100
912			\|a GBV_ILN_101
912			\|a GBV_ILN_105
912			\|a GBV_ILN_110
912			\|a GBV_ILN_120
912			\|a GBV_ILN_138
912			\|a GBV_ILN_150
912			\|a GBV_ILN_151
912			\|a GBV_ILN_152
912			\|a GBV_ILN_161
912			\|a GBV_ILN_170
912			\|a GBV_ILN_187
912			\|a GBV_ILN_213
912			\|a GBV_ILN_230
912			\|a GBV_ILN_267
912			\|a GBV_ILN_285
912			\|a GBV_ILN_293
912			\|a GBV_ILN_370
912			\|a GBV_ILN_602
912			\|a GBV_ILN_636
912			\|a GBV_ILN_702
912			\|a GBV_ILN_711
912			\|a GBV_ILN_2001
912			\|a GBV_ILN_2003
912			\|a GBV_ILN_2004
912			\|a GBV_ILN_2005
912			\|a GBV_ILN_2006
912			\|a GBV_ILN_2007
912			\|a GBV_ILN_2008
912			\|a GBV_ILN_2009
912			\|a GBV_ILN_2010
912			\|a GBV_ILN_2011
912			\|a GBV_ILN_2014
912			\|a GBV_ILN_2015
912			\|a GBV_ILN_2020
912			\|a GBV_ILN_2021
912			\|a GBV_ILN_2025
912			\|a GBV_ILN_2026
912			\|a GBV_ILN_2027
912			\|a GBV_ILN_2031
912			\|a GBV_ILN_2034
912			\|a GBV_ILN_2037
912			\|a GBV_ILN_2038
912			\|a GBV_ILN_2039
912			\|a GBV_ILN_2044
912			\|a GBV_ILN_2048
912			\|a GBV_ILN_2049
912			\|a GBV_ILN_2055
912			\|a GBV_ILN_2057
912			\|a GBV_ILN_2059
912			\|a GBV_ILN_2061
912			\|a GBV_ILN_2064
912			\|a GBV_ILN_2065
912			\|a GBV_ILN_2068
912			\|a GBV_ILN_2070
912			\|a GBV_ILN_2086
912			\|a GBV_ILN_2088
912			\|a GBV_ILN_2093
912			\|a GBV_ILN_2106
912			\|a GBV_ILN_2107
912			\|a GBV_ILN_2108
912			\|a GBV_ILN_2110
912			\|a GBV_ILN_2111
912			\|a GBV_ILN_2112
912			\|a GBV_ILN_2113
912			\|a GBV_ILN_2116
912			\|a GBV_ILN_2118
912			\|a GBV_ILN_2119
912			\|a GBV_ILN_2122
912			\|a GBV_ILN_2129
912			\|a GBV_ILN_2132
912			\|a GBV_ILN_2143
912			\|a GBV_ILN_2144
912			\|a GBV_ILN_2147
912			\|a GBV_ILN_2148
912			\|a GBV_ILN_2152
912			\|a GBV_ILN_2153
912			\|a GBV_ILN_2188
912			\|a GBV_ILN_2190
912			\|a GBV_ILN_2232
912			\|a GBV_ILN_2336
912			\|a GBV_ILN_2433
912			\|a GBV_ILN_2446
912			\|a GBV_ILN_2470
912			\|a GBV_ILN_2474
912			\|a GBV_ILN_2507
912			\|a GBV_ILN_2522
912			\|a GBV_ILN_2548
912			\|a GBV_ILN_4035
912			\|a GBV_ILN_4037
912			\|a GBV_ILN_4046
912			\|a GBV_ILN_4112
912			\|a GBV_ILN_4125
912			\|a GBV_ILN_4242
912			\|a GBV_ILN_4246
912			\|a GBV_ILN_4249
912			\|a GBV_ILN_4251
912			\|a GBV_ILN_4305
912			\|a GBV_ILN_4306
912			\|a GBV_ILN_4307
912			\|a GBV_ILN_4313
912			\|a GBV_ILN_4322
912			\|a GBV_ILN_4323
912			\|a GBV_ILN_4324
912			\|a GBV_ILN_4325
912			\|a GBV_ILN_4326
912			\|a GBV_ILN_4328
912			\|a GBV_ILN_4333
912			\|a GBV_ILN_4334
912			\|a GBV_ILN_4335
912			\|a GBV_ILN_4336
912			\|a GBV_ILN_4338
912			\|a GBV_ILN_4393
912			\|a GBV_ILN_4700
936	r	v	\|a ELIB24
951			\|a AR
952			\|d 84 \|j 2019 \|e 5 \|b 03 \|c 09 \|h 993-1001

Population pharmacokinetics of siltuximab: impact of disease state

Zugang & Verfügbarkeit

Zugehörige Publikationen/Bände