Table 2.

Summary of in vivo work showing concentrations producing analgesia and/or toxicity after intrathecal infusion, flare after intradermal delivery in dogs.

	MW	Human and dog IT Analgesia Antispasticity a,b	Reference	IT canine toxicologyb	Reference	In vivo: canine Intra- dermal Flare c	j
		mg * mL−1/mM		mg * mL−1/mM		mg/mL−1/mM
Adenosine	267	0.25/ H,B		> 3/11	(Chiari et al., 1999)	1/3.7	j
Alfentanil Citrate	529	4/7.6 C,I	(Yaksh et al., 2012)	> 20/ > 38	(Yaksh et al., 2012)	> 20/ > 38	(Yaksh et al., 2012)j
Baclofen HCl	213	1/4.7, C,I 0.3/9.4 H,I c	(Sabbe et al., 1993) (Boster et al., 2016)	> 2/ > 9.4	(Sabbe et al., 1993)	> 4/19	j
Bupivacaine HCl	325	1.5/ 4.6 C,I 7.5/23 H,I	(Kroin et al., 1987)	> 3.7/ > 11.4	(Kroin et al., 1987)	50/154	j
Clonidine HCl	267	2.5/9.4 C,I 0.12/0.4 H,I	(Kroin et al., 1987; Kroin et al., 2003) (Uhle et al., 2000)	> 2/ > 7.5	(Kroin et al., 2003)	10/38	j
DPDPE	645	3/4.6 C,I	(Horais et al., 2003)	6/9.3	(Horais et al., 2003)	10/16	j
Fentanyl Citrate	529	0.3/0.6 H,I 0.1/ H,Id	(Allen et al., 2006b) (Willis and Doleys, 1999)	> 2/ > 3.8	(Allen et al., 2006b)	> 2/ > 3.8	j
Gabapentin	171	ND		80 mg/mLf	Hildebrand, unpubg	> 10/ > 59	j
Hydromor phone HCl	322	0.1/0.3	(Allen et al., 2006b)	3/9.3	(Allen et al., 2006b)	1/3.1	j
Ketamine HCl	274	ND		4.2/15	(Yaksh et al., 2008)	10/36	j
Lidocaine HCl	271	ND		ND		50/185
Methadone HCl	346	3/8.6 C,I	(Allen et al., 2006b)	1/2.9	(Allen et al., 2006b)	10/29	(Yaksh et al., 2013a),j
MK-801	337	ND		0.4/1.2	(Yaksh et al., 2008)	6/18	j
Morphine Sulfate	329	0.1/0.3 C,I	(Allen et al., 2006b)	3/9.1	(Yaksh et al., 2003)	0.1/0.3	(Yaksh et al., 2013a), j
Morphine 3 gluc	461	ND		ND		1/2.2
Morphine 6 gluc	461	ND		ND		10/22
Neostigmine Methylsulfate	334	0.075/0.22, H,B	(Lauretti et al., 1998)	> 1/ > 3.0	(Yaksh et al., 1995)	10/30
ST-91 HCl	253	4/15.8 C,I	Yaksh, unpubh	< 18/ < 71	Yaksh, unpubh	1/4.0
Tizanidine HCl	290	2.5/9.4 C,I	(Kroin et al., 2003)	6/20.6	(Kroin et al., 2003)	10/34
Ziconotide	2639	< 0.001/0.0004 C,Ii 0.003e/0.001 H,I	(Wermeling et al., 2003; Yaksh et al., 2012; Deer et al., 2017a)	> 0.006i	(Skov et al., 2007)	0.020/0.008

^aDoses represent best estimates based on reported doses or the mean of a distribution.

^bH: human; C: Canine: B: bolus; I: Infusion.

^cDelivered in 2 mg/mL.

^dper day.

^eDose is 0.005 mg/24 h.

^fCarried out in sheep.

^gKeith Hildebrand, Medtronic, personal communication.

^hT.L. Yaksh, unpublished observations.

ⁱmg/h.

^junpublished data in this paper.