Tabular highlights gives a high level view of how iPRECIO pumps were used/programmed in selected scientific publications in Applications Examples eBook. For more detailed view, refer eBook and publications . In e-book for example, Research Application 1 (RA1) on page 5 &6 of eBook is on row 1 of Tabular highlights – Chavan et al. The protocol is once a day infusion. RA2 on pages 7 & 8 (row 2 Kroon et al) has a 3 day stop prior to start of infusion of Nicotinic acid with the animal in the metabolic cage all of the time of the infusion protocol.

Research Application (RA), Author, doi:

Refillability of Pump
KVO/RCV

How pump programmed?
Intermittent
Circadian /Continuous
or bolus
Timed release

Vehicle and Drug(s)

Yes

SC

Adipose tissue-diabetes-drug therapyLipoysis and fatty acid metabolismGPR109A-Niacin-Tachyphylaxis
Zucker rat + SMP-200 Pump

5 or 11 days
infusion + 2 days
recoveryNoNointrathecal

Neural-stem cells-spinal cord injury
rat + SMP-200 Pump

14 days

Yes

No

No

intrathecal

Regulatory request, CNS end points(modified Irwin assessment)
rat + SMP-200 Pump

10 days

Yes

No

No

IV jugular

Cardiac, diastolic dysfunction, heart
failure, metabolism
dog + SMP-200 Pump

14 weeks

RA 2 Kroon et al. doi: 10.1194/jlr.M058149
pgs 7-8 of eBook

Pump programmed tostop for 3 days

Nicotinic Acid (NiAc) or saline
5 days of continuous or intermittent (12 hr ON/OFF cycles, infusion on 13:00h)

Yes

Yes

RA 3 Suehiro et al. doi:10.1038/srep04972
pgs 9-10 of eBook

No

PKA and ATP - solution change every 2 days
1ul/hourYes

1ul/hr saline for 1 week Test articles infusing at 30ul/hr for 72 hours after 1ul/hr saline recovery after catherization
for full recovery
and pump implantation

DurationSC

1 week recovery

Pumps programmed to infuse saline (2ul/hr) or ßOHB (2ul/hr) or sodium pyruvate (5ul/hr)
or coconut oil (5ul/hr) prior to meal time (6h, ZT22-ZT) in Restricted Food (RF)

http://www.abstractsonline.com/Plan/ViewAbstract.aspx?mID=2964&sKey=87d8b951-316f-466a-9eb74b154d0bbd2c&cKey=b4b8338f-9bd2-44e2-bcf4-6e05a36cbbcb&mKey=%7b70007181-01C9-4DE9-A0A2EEBFA14CD9F1%7d

Key words

Biological sciences-NeuroscienceBiochemistry
Mice + SMP-300 iPRECIO Pump

RA 1 Chavan et al. doi:10.1038/ncomms10580
pgs 5-6 of eBook

RA 4 Mitchell et al. Developments in LifeSciences Vol. 14
No. 4

Adminstration
Site

No

Yes

Yes

< 3 weekspgs 11-12 of eBook
RA 5 Asemu et al. DOI: 10.1152/ajpheart.00674.2012
pg 13 of eBook

RA 6 Thisgaard et al. DOI: 10.7150/thno.15898
pg 14 of eBook

No

No

Author, doi:
GLP Studies with iPRECIO Pumps (page 15 eBook)
Patten et al
pg 15 of eBook
Perron et al
pg 15 of eBook

1ul/hr artificial CSF

Ringer et al
pg 15 of eBook

Saline when notinfusing test article

No

Aldosterone (15% ethanol 50% DMSO and 35% water) was continuous infused

Yes

No

No

Glioblastoma, Auger-electron therapy,
125
Brain infusion convection delivery, [ I}5-Iodo-2'deoxyuridine, temozolomide, SMP-200
Pump

Treament period 30ul/hour for 72 hours

No

Yes

Yes

intrathecal

Flow-rate and dosing validation studies on the bench

No

Yes

Yes

in-vitro

2 hour baseline, 2 hour infusion (Milrinone or vehicle)

No

Yes

Yes

right jugular
vein

Yes

No

No

IV jugular

Infusion pump, implantation, rat,
iPRECIO, Physiological condition
SMP-200 pump

4 or 13 weeks

scdrug delivery, minipump, osmotic
pumps, implantable pump, dose
response, quantitative pharmacology, preclinical, telemetry
rat + SMP-200 pump

30 daysIVdrug delivery, minipump, osmotic
pumps, implantable pump, dose
response, quantitative pharmacology, preclinical, telemetry
rat + SMP-200 pump

30 daysisotone saline, 0.1 mM MTX, then 0.3µg/ml

125

I-UdR,

127

I-UdR was continuously infused

CNS (modified Irwin assessment)
rat + SMP-200 pump
GLP validation
GLP validation, jacktet, ambulatory,
cardiovascularDog + iPRECIO Dual

10 days

3 days for TA< 7 days
24 hours

Author, doi:
Toxicology with iPRECIO pumps (page 15 eBook)
Tsuboi et al. http://doi.org/10.2131/fts.3.1
pg 15 of eBook

No but full study saline Saline infusion for 4 weeks and 13 weeks
infusion
2 or 2.5ul/hour

Application (PA), Author, doi:
Application Examples
pg 16 of eBook

AP1 Tan et al. 5-HT doi: 10.3389/fphar.2011.00044
pg 16 of eBook

AP2 Tan et al. dobutamine doi:
10.3389/fphar.2011.00044
pg 16 of eBook

3 days pump "OFF"(0.2ul/hour) , forcontrol cardiovascularparameters

5-HT dose response with control periodNo

11 day recovery period Saline, dobutamine and verapamil infusions

No

Page 1 of 5

Yes

Yes

Yes

Yes

Research Application (RA), Author, doi:

Refillability of Pump
KVO/RCV

How pump programmed?
Intermittent
Circadian /Continuous
or bolus
Timed release

Vehicle and Drug(s)AP3 Zaretsky et al.
http://www.abstractsonline.com/Plan/ViewAbstract.aspx?mID=2964&sKey=87d8b951-316f-466a-9eb74b154d0bbd2c&cKey=b4b8338f-9bd2-44e2-bcf4-6e05a36cbbcb&mKey=%7b70007181-01C9-4DE9-A0A2EEBFA14CD9F1%7d

5 day recovery but noflow

BMI (0.1 mM) 100 nl injections

No

Yes

AP4 Kuroki et al. DOI: 10.1152/ajpheart.00922.2013
pg 16 of eBook

AP5 Gey et al. doi:10.1016/j.nbd.2016.03.012
not in eBook

5ul/hour continous infusion of Ang II. Comparison made with Alzet Pump and Havard Sringe
pump

Yes

no

Key words

DurationYeshypothalamas, cardiovasular, micro
intrainjections
hypothalamicrat + SMP-200 pumpseveral daysNosalt-sensitive hypertension; angiotensin
II-salt hypertension; Alzet salt-sensitiveSChypertension;
administration
minipump; iPrecio pump; plasma
angiotensin II

2 weeks Ang II
infusion

Bilateral
minipump; iPrecio pump; plasma
infusion into
angiotensin II
STN or anterior
Rats, SMP-200
SNr

3 or 4 week

pg 16 of eBook

7 to 10 days recovery
then 4 days control
periodAdminstration
Site

no RCV

0.2 ul/hr continuos infusion. Stability of vigabatrin was tested and confirmed for 5 weeks

yes

no

no

RCV or KVO not
discussed

2 pumps (SMP-200 & SMP-310R) 3 tool compounds, 24 doses, 7 infusion rates (2.2ul/hr to
20 ul/hr)

Yes

No

No

iv, external
jugular vein

PK/PD, oncology, tool compounds,
validation, programmable pump

12-13 days

No

Intra-cranial
infusion

Cancer,orthotopic,glioblastoma,
bioluminecscence
Nude rats, SMP-200

22 daysYes

endocrinology
vitamin B12, BBB, reduction of foodsubcutaneous
intake, peptides
rats, SMP-200 pumps

5 or 10 days

Yes

endocrinology
vitamin B12, BBB, reduction of foodsubcutaneous
intake, peptides
rats, SMP-200 pumps

5 or 10 days

Webinar (WE), Author, www or doi
Webinar: Compound Delivery, PK-PD & Validation
Studies in Oncology Studies. Schnell et al.
http://www.insidescientific.com/webinars/item/384-gold-standardphysiological-measurements-and-novel-drug-delivery-methods-ipreciopg 17-18 of eBook

WE 1 Schnell
http://www.insidescientific.com/webinars/item/384-gold-standardphysiological-measurements-and-novel-drug-delivery-methods-ipreciopg 17-18 of eBook

Saline infusion for
On day 21 (tumor reached certain size), infusion of Compound A for 22 days. Behaviour andtumor size to grow to aweight gain not impaired versus control without subcutaneous pumpcertain size (12th day)

7 days recovery Saline
5 days baseline Saline
5 day TA or 10 day TA

Vitamin B12 Conjugation of Peptide-YY3–36 or
Native Peptide-YY3–36 or saline
5 pulses per day; three 1 hour pulses of 10 nmol.kg-1.h-1 (20 μl.h-1) with three hours
between pulses and two 1 hour pulses of 5 nmol.kg-1.h-1 (10 μl.h-1) with five hours
between pulses

Henry et al. DOI: http://dx.doi.org/10.1210/en.2014-1825 7 days recovery Saline(WE 2)
5 days baseline Saline
pg 18 of eBook
5 day TA or 10 day TA

Vitamin B12 Conjugation of Peptide-YY3–36 or
Native Peptide-YY3–36 or saline
5 pulses per day; three 1 hour pulses of 10 nmol.kg-1.h-1 (20 μl.h-1) with three hours
between pulses and two 1 hour pulses of 5 nmol.kg-1.h-1 (10 μl.h-1) with five hours
between pulses

WE 2 Doyle
http://www.insidescientific.com/webinars/item/384-gold-standardphysiological-measurements-and-novel-drug-delivery-methods-ipreciopg 17-18 of eBook

Additional Highlights, doi

Page 2 of 5

Yes

No

No

No

Yes

Yes

Research Application (RA), Author, doi:

Refillability of Pump
KVO/RCV

How pump programmed?
Intermittent
Circadian /Continuous
or bolus
Timed release

Vehicle and Drug(s)Development of the pregnant rat model for labor induction and augmentation with Oxt. The
system consists of a subcutaneously placed iPRECIO infrared-controlled microinfusion pump
Giri, Tusar, et al. "Labor induction with oxytocin in(SMP-200, Primetech Corporation) connected to the right internal jugular vein in an
pregnant rats is not associated with oxidative stress in theembryonic day (E)18 Sprague Dawley dam (Charles River Laboratories) (Fig. 2). Briefly, theYes, dose
fetal brain." Scientific reports 12.1 (2022): 1-12.
dam was anesthetized with 2% isoflurane followed by subcutaneous implantation of theescalation. 4
KVO function not used iPRECIO pump approximately 2–3 cm below the nape of the neck and creation of a tunnel toNodoses or flowhttps://www.nature.com/articles/s41598-022-07236-x
deliver the pump tubing next to the internal jugular vein, into which it was secured in place
rateswith ligatures. The reservoir of the iPRECIO pump was primed with sterile normal saline
Page 22 of eBook.
prior to implantation and was pre-programmed to deliver an infusion rate of 10 μl/h for 72
h to keep the tubing patent until E21. Two hours before completion of the saline infusion at
72 h, the reservoir was accessed subcutaneously under brief isoflurane anesthesia toaspirate the saline and was refilled with 900 μl of Oxt (Selleck Chemicals, 50 μg/mL in
normal saline). This was followed by the pre-programmed infusion rate of 5 μl/h for 4 h, 10
μl/h for 4 h, 20 μl/h for 4 h, and 30 μl/h for 12 h (iPRECIO Management System)(Supplementary Fig. S2).
Dey et al. DOI
https://www.ahajournals.org/doi/10.1161/CIRCRESAHA.1
18.312708

No

Page 25 of eBook.

Steplewski et alhttps://onlinelibrary.wiley.com/doi/abs/10.1002/jor.2336
9

No

Daily bolus of Isoproterenol (ISO) was administered via implantation of a programmable
iPRECIO® Pump in the peritoneal cavity. The iPRECIO pump enables reliable, timed deliveryof pharmacological agents. The pump was programmed for 1 hour delivery of Isoproterenol
at 30μl/hr, total dose of 2mg/kg/day, once a day at the same time (1 PM).

The delivery of the ACA and P-ACA started immediately after surgery and continued for 8
weeks at 1ul/h.

no

No

Yes

Adminstration
Site

IV right jugular

Yes

IP

Key words

Duration

Subjects
Preclinical research
Translational research

ventricular fibrillation, phosphorylation,
proteomics, heart failure, reactive
oxygen species, mitochondria

3 to 5 weeks

300g hartley guinea pig, SMP-200

Yes

No

No

injured knee
joint

joint contracture, posterior capsulecollagen, collagen fibrils, arthrofibrosis,
antibody

8 weeks

New Zealand White Rabbits, 8-12mths,
SMP-200

New: Not referenced in E-Book

Contact Primetech for eBook
https://www.iprecio.com/contact/form/tabid/231/Default.aspxJul-22For more details on applications, see bibliography section (here) and iPRECIO® Application and Technology Report (here)

Continuous delivery of lenalidomide and otherimmunomodulatory agents
Mouse Update 1 (MU1) Borovinskaya et al. US Patent
Application US 2020/0330445A1

24 hour stop after
surgery before drugdelivery then 4ulhr.

See Example 1
Replace pump after 2
https://patents.google.com/patent/US20200330445A1/e weeks, 24 stop aftern?q=iprecio&q or https://lnkd.in/gerJdDA
surgery before
continuing
pg 27 of eBook

SCID mice, average weight of mice - 20g
24 hour stop after surgery before drug delivery then 4ulhr. Replace pump after 2 weeks, 24
Yesstop after surgery before continuing

Page 3 of 5

No

No

SC

continous infusion

28 daysResearch Application (RA), Author, doi:

Refillability of Pump
KVO/RCVAn adipokine feedback regulating diurnal food intake
rhythms in mice
Mouse Update 2 (MU2) Tsang et al.
Tsang et al. eLife 2020;9:e55388.
DOI: https://doi.org/10.7554/eLife.55388

2 weeks recovery
0.5ul/hrCite as: eLife 2020;9:e55388 DOI: 10.7554/eLife.55388
https://elifesciences.org/articles/55388

How pump programmed?
Intermittent
Circadian /Continuous
or bolus
Timed release

Vehicle and Drug(s)After 2 weeks of recovery (MT experiment; Figure 4) or after 6 weeks of HFD (WT HFD
experiment; Figure 6), infusion of
AdipoRon (1 mg/ml) or vehicle (DMSO/aCSF/PEG-400) was started, either cyclically with
infusions starting at ZT13 for 10 hr followed by 14 hr of inactivity or constantly with amaximal flow of 0.5 ul/hr (for treatment regimens see Figures 4A and 8A).

Adminstration
Site

Key words

Duration

8-week-old Adipoq-/- or WT mice.
Yes

Yes

Yes

ICV

No

Yes, precise
timing withicv
respect to clinicalsigns.

Circadium rhythms, Adipoq-deficient
mice or wild-type mice - 8 weeks of age

3 weeks of rhymic
or constant icv

Pumps were re-freshed every 7-8 days and 3-4 days after re-freshing, feeding data taken at
the appropriate time - ZT4-6.

pg 28 of eBook(i) a flow rate of 0.1
ll/h, to keep the pump
A combination of two human monoclonal antibodies cures delivering PBS from thesymptomatic rabies
day of surgery on; (ii) a The pumps were activated the day before the surgery
flow rate of 1.0 ul/h, 2 using three infusion programs: (i) a flow rate of 0.1 ll/h, to keep the pump delivering PBS
MU3 Dias de Melo et al.
days before thefrom the day of surgery on; (ii) a flow rate of 1.0 ll/h, 2 days before the treatment, to allow
https://doi.org/10.15252/emmm.202012628
treatment, to allow
flow stability and dead volume elimination from the tubing (27.4 ll); and (iii) a flow rate offlow stability and dead 1.0 ll/h during 20 days to deliver the treatment.
pg 28 of eBook
volume eliminationfrom the tubing (27.4
ul)

Sympathetic Overactivity in CKD Disrupts Buffering of
Neurotransmission by Endothelium-Derived
Hyperpolarizing Factor and Enhances Vasoconstriction
MU4 Cao et al.
DOI: https://doi.org/10.1681/ASN.2020030234
https://jasn.asnjournals.org/content/31/10/2312
pg 28 of eBook

N/A

To study the effects of inhibiting central sympathetic outflow, groups of 5/6Nx micereceived continuous intracerebroventricular (i.c.v.) infusions of clonidine (5.76 mg/kg perday; Sigma, St. Louis, MO)5 or artificial cerebral spinal fluid (Sigma) from the first day after
operation for 4 weeks, using Micro Infusion Pumps (iPrecio SMP/IMS-310R model, Durect
Corporation, Cupertino, CA). Micro Infusion Pumps were implanted in mice underanesthesia 7 days before the 5/6Nx operation, and were programmed wirelessly using
proprietary iPrecio pump software (Durect Corporation). The accuracy of the i.c.v. infusion
was confirmed by the tracer Evans blue.

yes

Male CD1 mice, 6 week old
Yes

No

No

icv

Vagus nerve stimulation mediates protection from kidney
ischemia-reperfusion injury through α7nAChR+
splenocytes
During the recovery
One day before LPS infusion, mice were anesthetized (ketamine [120mg/kg] and xylazine
period, normal[12 mg/kg]) and the left cervical vagus nerve (uncut) was electrically stimulated (50 μA, 5
MU5 Inoue et al.
saline was continuously
YesHz, 1 ms) for 10 minutes as described above. At the infusion start time, normal saline in thehttps://doi.org/10.1172/JCI83658
infused at the rate of 1
microinfusion pump was changed to the LPS solution (10 μg/ml) under isoflurane
https://www.jci.org/articles/view/83658
μl/h for 4 days.
anesthesia. LPS was infused at the rate of 10 μl/h for 3 hours. At the end of infusion, mice
were anesthetized (ketamine [120 mg/kg] and xylazine [12 mg/kg]) and blood was collected
pg 28 of eBookfrom the periorbital sinus. Plasma TNF-α was measured with a commercially available ELISA
kit (Affymetrix).

Male CD-1 mice (6 weeks old) weighing
4 weeks
20–24 g were obtained
from the Institutional Animal ExperimentCenter.

C57BL/6J
male mice

The catheter part of the microinfusion pump was inserted
into the left external jugular vein via a midcervical incision. The main body of the
microinfusion pump was implanted s.c. in the lumbar region.

Page 4 of 5

Eight-week-old female SPF Balb/cJRjmice

20 days delivery ofantibody cocktail
following saline
infusion for 2-3
days.

No

No

IV jugularMice. Male mice (8–12 weeks of age,
20–25 g) were used for all experiments.
WT C57BL/6 mice were purchased fromthe National Cancer Institute, Chrna7–/– 10ul/hr for 3 hours(referred to as α7KO) mice (B6.129S7LPS
Chrna7tm1Bay/J)
were obtained from JacksonLaboratories, and WT (Chrna7+/+)progeny were used as controls inexperiments depicted in Figures 8 and
10.

Research Application (RA), Author, doi:

Refillability of Pump
KVO/RCV

Pulsative gnrh administration for treating cognitive
disorders
MU6 PREVOT et al.
International Publication Number WO 2020/221821 A1;https://patents.google.com/patent/WO2020221821A1/e N/A
n?q=PULSATIVE+GNRH+ADMINISTRATION+FOR+TREATIN
G+COGNITIVE+DISORDERS&oq=PULSATIVE+GNRH+ADMINISTRATION+FOR+TREATING+COGNITIVE+DISORDERS
pg 28 of eBook

Discovery, Preclinical Characterization, and Early Clinical
Activity of JDQ443, a Structurally Novel, Potent, andSelective Covalent Oral Inhibitor of KRASG12CMU6MU6 Andreas Weiss et al.
https://aacrjournals.org/cancerdiscovery/article/12/6/15
00/699171/Discovery-Preclinical-Characterization-andEarly
Weiss, Andreas, et al. "Discovery, Preclinical
Characterization, and Early Clinical Activity of JDQ443, a
Structurally Novel, Potent, and Selective Covalent Oral
Inhibitor of KRASG12C." Cancer Discovery 12.6 (2022):
1500-1517. [Open Access]Unknown (notdescribed in detail)How pump programmed?
Intermittent
Circadian /Continuous
or bolus
Timed release

Vehicle and Drug(s)Pulsatile GnRH infusion reverses both olfactory- and cognitive-related impairments in
Ts65Dn mice. (A) Schematic diagram illustrating the pharmacological therapy performed in
adult Ts65Dn mice with LUTRELEF®, a GnRH peptide of clinic use. Mice were implanted withosmotic pump, to receive a continuous infusion of vehicle or LUTRELEF® (0.25 pgr/ 3h); orwith a programmable mini-pump (iPRECIO), to receive a pulsatile LUTRELEF® infusion (every
3 hours; a peak of 0.25 pg with peak duration of lOmin). (B-F) Representative graphs for LH
pulsatility assessment after 15 days of vehicle or LUTRELEF® subcutaneousNoadministration. LUTRELEF® pulsatile infusion in Ts65Dn males significantly increased LH
pulse frequency and LH pulse amplitude (G) compared to LUTRELEF® continuous infusion
which prevented both LH pulse frequency and LH pulse amplitude both in WT and Ts65Dnmice(G). LUTRELEF® pulsatile infusion rescued the capacity to discriminate between
different
odors (H) and cognitive deficits (I) in Ts65Dn mice. *p < 0.05; ** p < 0.01; *** p < 0.001.

To assess the effect of continuous dosing on tumor growth, LU99 tumor–bearing nude mice
were implanted subcutaneously with a programmable microinfusion pump (iPRECIO,
SMP310R, Primetech Corporation) as previously described (56). For this purpose, thecatheter connected to the microinfusion pump was inserted into the left external jugularvein via midcervical incision, and the body of the microinfusion pump was implanted
subcutaneously on the flank of the mice opposite to the xenograft tumor. For infusion,
JDQ443 was dissolved in 30% PEG and 10% Kolliphor at a concentration of 3 and 10 mg/mL.
The infusion rate of 4 μL/h was programmed with iPRECIO Management Software v1.0.4.0.
Pumps were refilled with vehicle or JDQ443 daily. At days 2 to 3, 9 to 10, and 12 to 13,
the drug released was quantified in blood samples collected at the tail vein by LCMS/MS. “excerpt without modification according to Attribution-Non Commercial-No
Derivatives 4.0 International (CC BY-NC-ND4.0) https://creativecommons.org/licenses/bync-nd/4.0/

Page 5 of 5

Yes

Yes

Yes

No

Adminstration
Site

ICV

No

IV external
jugular vein

Key words

mouse model of Down syndrome (DS Ts65Dn mice)Mice were
kept under optimal hygiene conditions inindividually ventilated
cages under 12-hour dark/12-hour light
conditions and had accessto sterilized food and water ad libitum.
Subcutaneous tumors were
induced by injecting cells in HBSS
containing 50% BD matrigel
in the flank of female athymic
Crl:NU(NCr)-Foxn1nu-homozygous
nude mice (Charles River; MIA PaCa-2,
NCI-H2122, NCI-H441
5 × 106; LU99 2 × 106) or female
CB17.Cg-PrkdcscidLystbg-J mice(Charles River; KYSE410 10 × 106).
Subcutaneous NCI-H2030 and
HCC44 tumors were induced bytransplantation of tumor fragmentsin the flank of female C.B-Igh1b/GbmsTac-Prkdcscid-Lystbg
N7 mice (Taconic).

Duration

2 weeks

13 days at least