Monoclonal antibody exposure in rat and cynomolgus monkey cerebrospinal fluid following systemic administration

Table 1 Pharmacokinetic parameters of antibodies A, B, C, D and E in rodents and non-human primates

Test article	Animal info	Dose	Serum PK parameters^a				CSF PK parameters^a				^CSFAUC/^SerumAUC ratio (%)
		Dose	^serumC ^c_max	^serumT ^c_max	^serumAUC_INF	^serumt_½	^CSFC ^c_max	^CSFT ^c_max	^CSFAUC_INF	^CSFt_½
		mg/kg	μg/mL	H	μg*h/mL	H	ng/mL	H	ng*h/mL	H
A	Rat^b	10 (IV)	560		40,400	155	200	16	38,000	185	0.09
B	Rat^b	10 (IV)	208		31,700	234	110	24	48,400	245	0.15
C	Rat^b	20 (IV)	778		108,500	169	380	48	94,000	136	0.09
D	Rat^b	20 (IV)	559		67,100	173	170	24	48,000	143	0.07
E	Rat^b,d	30 (IP)	1000	6	71,000	80	340	24	54,000	44	0.075
A	NHP (N = 4)	20 (IV)	520 ± 35		171,400 ± 23,100	402 ± 39	590 ± 270	42 ± 36	258,000 ± 124,600	423 ± 44	0.15 ± 0.07
A	NHP (N = 11)	100 (IV)	2270 ± 650		854,700 ± 266,500	456 ± 87	2670 ± 2060	43 ± 30	1,441,200 ± 798,100	531 ± 152	0.16 ± 0.08
C	NHP (N = 11)	30 (IV)	1220 ± 390		163,200 ± 36,000	156 ± 34	680 ± 710	48 ± 29	140,300 ± 73,300	201 ± 71	0.09 ± 0.06
C	NHP (N = 6)	100 (IV)	4210 ± 790		467,300 ± 76,500	126 ± 31	2210 ± 810	64 ± 29	538,300 ± 231,300	181 ± 39	0.10 ± 0.05
D	NHP (N = 4)	30 (IV)	980 ± 70		179,700 ± 22,400	290 ± 35	580 ± 240	60 ± 24	194,400 ± 106,800	257 ± 44	0.10 ± 0.04

^aPharmacokinetic calculation was based on linear-log noncompartmental analysis for both CSF and serum profiles
^b Rat PK parameters were based on mean data
^c Maximum serum and CSF levels were based on the highest observed serum and CSF concentration, respectively
^d Pharmacokinetic parameters from Ref. [7]

ISSN: 2045-8118