Selected quotes extracted from scientific publications describing the use of ALZET® Osmotic Pumps as the method of agent administration.

“ The subcutaneous implantation of the drug-containing osmotic minipumps enabled the continuous administration of paroxetine…and succeeded in maintaining the mouse plasma paroxetine concentrations within therapeutic levels.”(p. 158)

Hirano, K, et al. Brain Research. 2005; 1053:154-161

“ Mice were exposed to THQ PFTI's via osmotic pumps to deliver a controlled and constant amount of drug. This approach has the advantage that one can explore the in vivo efficacy of the THQ compounds prior to optimization of compounds for desirable pharmacokinetic properties.” p. 3709

Nallan, L, et al. J. Med. Chem. 2005; 48:3704-3713

“The animals tolerated the appliance and the implanted mini-osmotic pump well. The incision wound from the implantation of the mini-osmotic pump was adequately healed by the day following surgery.” (p. 217)

Mavragani, M, et al. Eur J. Orthodontics. 2005; 27:215-225

“The advantage of using mini-osmotic pumps is that, unlike injections, they are not associated with frequent handling of the animal, which can lead to stress and modify the animals vestibular proprioceptive and visual information.” (p. 1127)

Gliddon, C.M., et al. JPET. 2005; 313(3):1126-1135

“The inherent simplicity of osmotic pumps makes them an excellent replacement for electromechanical pumps, especially for extended sampling periods in harsh aquatic environments.”(p. 103)

Jannasch, H.W., et al. Limnology and Oceanography: Methods. 2004; 102-113

“By eliminating constrains of intraperitoneal (i.p.) bolus reinjections of substrate, the implanted pump allowed continuous real-time molecular imaging of reporter activity throughout the time course of a multi-day experiment, while simultaneously allowing rapid temporally resolved analysis of short time constraints that characterize drug action. This innovation should be generalizable to a variety of other imaging strategies in vivo.” (p. 613)

Gross, S., et al. Nature Methods. 2005; 2(8): 607-614

“In summary, our data demonstrate that the local microinfusion of endostatin is able to inhibit tumor growth and increase survival of animals with orthotopic malignant gliomas.  Local continuous i.c. delivery is more effective than daily systemic delivery.” ( p.1255) Schmidt et al., Clinical Cancer Research 2004;10:1255-1262.

“Galantamine was administered via…osmotic pump… A minipump was used in order to better mimic the daily multiple dosing regimen given to patients with Alzheimer’s disease.” Wenk et al., European Journal of Pharmacology 2003;453:319-324.

 “Nonspecific toxicity is a common problem associated with in vivo application of antisense oligonucleotides.  However, by employing certain strategies including the use of partial rather than complete phosphorothioate modification, reducing the length of the oligonucleotide, and using a steady continuous infusion rather than bolus injections, we were able to minimize such toxicity (Van Kampen & Stoessl, 2000a).” (p. 309) Van Kampen et al., Neuroscience 2003;116:307-314.

“In preliminary studies using this model, we observed severe side effects with 5-FU doses beyond 25 mg/kg biweekly injections (mice developed skin ulcers, bleeding and severe diarrhea). Thus, we chose to deliver 5-FU by continuous infusion at an equivalent cumulative dose in order to minimize toxicity. Additionally, studies have demonstrated an increased efficacy of chemotherapeutic agents when administered continuously.” Stoeltzing et al. Int. J. Cancer 2003;104:496-503.

 “This study showed that pump-controlled delivery of a Nogo-A-specific antibody (7B12) initiated 24 hours after experimental stroke promoted improvement of long-term neurologic outcome in normotensive and SHR rats.” Wiessner et al, J Cereb Blood Flow Metab 2003;23(2):162.

“Nicotine was chronically administered subcutaneously to rats via osmotic mini-pumps. This model was proved to be a convenient and efficacious alternative to multiple injections to mimic the chronic intake of smokers.” Cormier et al., Neuropharmacology 2003;44:642-652.

“We developed the optic nerve/osmotic pump infusion technique to deliver soluble ligands, agonists, or antagonists directly into the optic nerve.  The advantages of this technique are that the infused drugs remain largely confined within the experimental nerve, reducing the impact of potential systemic side effects; mere placement of the catheter and subsequent infusion of the vehicle solution do not promote lesion-like changes within the optic nerve…” Rodgers et al., GLIA 41:180-190; 2003.

“A continuous infusion paradigm was utilized in both experiments to minimize any potential hemodynamic side effects from bolus NTG administration…” Cha et al., Pharm Bioch and Behav 2003;74:551-557.

“In the majority of studies examining nicotine withdrawal, nicotine was delivered by an osmotic pump… The osmotic pump allows for the continuous delivery of nicotine at a controlled rate for a specified amount of time. An advantage of this delivery protocol is that nicotine levels in the bloodstream remain fairly constant, much like those of human chronic smokers. Discontinuing the delivery of nicotine by removal of the pump or interfering with nicotine’s effect on the central nervous system induces a withdrawal reaction… Accordingly, this experiment sought to replicate previous work using a rodent model of nicotine withdrawal developed by Malin et al. (1992) that has become widely used…, and which implements the osmotic pump as the nicotine delivery mechanism.” Besheer et al., Behavioral Neuroscience 2003;117(2):327-340.

 “However formoterol administered intraperitoneally twice a day did not influence LPS-induced premature delivery (data not shown).  Osmotic Pumps can maintain the blood concentration of formoterol for over 20h.  Thus, it may be of importance that formoterol was continuously and uniformly administered.” (p. 201) Shinkai et al., Reproduction 2003;125:199-203.

 “Insofar as multiple dosing is concerned, we propose that only administration by pump (or administration more than four times a day) can provide clinical-like occupancies for haloperidol, olanzapine, and risperidone.” Kapur et al., The Journal of Pharmacology and Experimental Therapeutics 2003;305:625-631.

“Pump implantation and subsequent infusion of either A-CSF or PAI-1 did not impair the mice’s ability to perform a previously learned motor task.” Seeds et al., The Journal of Neuroscience 2003;23(19):7368-7375.

“CsA and RAD were administered by ALZET minipumps, which we prefer because of the well-defined drug exposure.  It avoids the daily peaks and troughs of oral drug administration, which in many animal studies are not well defined.” Matsumoto et al., Trasplantation 2003;76:166-1170.

“This study demonstrates the value of osmotic pumps as effective delivery vehicles for drugs in wild demersal fish.” (p.1024). “We conclude that the administration of T3 by osmotic pumps is an effective means of creating experimental hyperthyroidism in wild Atlantic cod.  Similarly, the administration of methimazole, thiourea, or testosterone with osmotic pumps was effective in rendering cod hypothyroid.” (p.1025) Comeau et al., Transactions of the American Fisheries Society 2003;132:1021-1026.

“The infusion treatment using implanted ALZET-type osmotic mini-pumps proved to be superior to both S.C. and I.V. infusion applied twice a day for 2 weeks.” (p. 586) Szende et al., Anti-Cancer Drugs 2003;14:585-588.

 “Continuous administration of rhEndostatin resulted in more significant tumor regression than intermittent administration of the agent in the same model. This indicates that rhEndostatin, if administered in continuous fashion, could become an effective agent for treating patients with neuroblastoma in the future.” (p.1499) Kiroiwa et al., Journal of Pediatric Surgery 2003;38(10):1499-1505.

“Our studies also confirm previous observations from Kisker et al. indicating that continuous infusion of endostatin administration by osmotic pump improves its efficacy… This is inline with other observations indicating that effective delivery of other antiangiogenic drugs…requires continuous rather than bolus administration for prolonged periods of time…” (p.380) Capillo et al., Clinical Cancer Research 2003;9:377-382.

“Administration of anginex by osmotic mini-pumps gave the best results, compared to loco-regional injections, once- or twice-daily subcutaneous injections or slow-release alginate bead strategies.” (p.341) Mayo, K, Drugs of the Future 2003;28(4):337-346.

“Osmotic minipumps were chosen to avoid the high plasma nicotine concentrations and subsequent episodic fetal hypoxia/ischemia that can be produced by nicotine injections.” (p. 566) Neff et al., Circulation Research 2003;93:565-572.

“The infusion treatment with ALZET osmotic pumps proved to be superior to both twice daily injections or intravenous injections.” (p. 155) Tejeda et al., Cancer Detection and Prevention 2003;27:155-162.

“Angiostatin was administered through continuous infusion...the continuous administration of angiogenesis inhibitors has greater therapeutic efficacy than the more commonly used twice-daily injections.” (p. 80) Reijneveld et al., European Journal of Clinical Investigation 2003;33:76-81.

“…opioid and nonopioid analgesics were continuously infused from subcutaneously implanted osmotic mini-pumps, a convenient modality of drug delivery that allows for drug delivery at constant rate for prolonged periods of time without experimenter intervention.” Bruins Slot et al., Pharmacology, Biochemistry and Behavior 2002;72:943-951.

“One goal of the present studies was to find a safe way to continuously administer insulin to [rat] pups so that in the future we may examine the effects of this early exposure on adult animals.  The present studies indicate that subcutaneous insulin pellets are not suitable for this purpose, since rat pups do not tolerate them well.  On the other hand, it will be feasible to compare the long-term effects of receiving equivalent doses of insulin via daily injections or an osmotic minipumps.” Thompson et al., Can. J. Physiol. Pharmacol. 2002;80:180-192.

“Several approaches have been tested to improve the anti-tumor activity of cytotoxins and immunotoxins and to decrease toxicity and immunogenicity of these agents.”… “In our current study, we utilized a device for continuous infusion (ALZET pump) of drug as an alternate approach to increase the availability of drug. This approach resulted in improved anti-tumor effect and decreased toxic effects.” “Utilizing this device, IL-13 cytotoxin can be continuously administered systemically in body.” Kawakami et al., Molecular Medicine 2002;8(8):487-494.

“Moreover, the replacement of pumps is a relatively simple surgical procedure (Prieskorn and Miller, 200). Allowing longer-term (> 1 month) experiments to be performed.” Shepherd et al., Hearing Research 2002;172:92-98.

“Since purified FSH has a short half-life, the hormone is administered as regular injection in 12-hr intervals or constant infusion via a subcutaneously implanted osmotic minipump.” Popova et al., Molecular reproduction and development 2002;63:177-182.

“We found recently that 21 d of treatment of rats with SSRIs, at clinically relevant and stable serum concentrations (achieved by the use of osmotic minipumps), caused robust downregulation of the SERT.”… “Studies on the effects of chronic antidepressants on the SERT have resulted in inconsistent reports (Owens and Nemeroff, 1998). Among the factors that may contribute to such inconsistency is the route of drug administration. In most studies of chronic administration of Ads to rats, the drugs are given intraperitoneally or subcutaneously, either once or twice daily. As rats metabolize these drugs more rapidly than humans, such dosage schedules can result in appreciable fluctuations in the serum concentration of drug throughout the day. For certain pharmacologic effects, sustained drug action may be needed” Benmansour et al. The Journal of Neuroscience 2002; 22(15):6766-6772.

“In order to investigate the in vivo role of MMPs, we established a rodent model of glioma progression… We chose continuous infusion using an osmotic pump as the method for delivering TIMP into the tumor. This paradigm allowed aggressive glioma development and circumvented the problem of the blood brain barrier disturbing reagent delivery following intravenous delivery.” Takahashi et al., Pharmacological Research 2002;46(2):155-163.

“Considering the secretion rate of CSF in rats (120 to 320 ul/h), this low rate of infusion – 0.5ul/h – was not likely to affect CSF pressure.” Wang et al., Hypertension 2002;40:96-100.

“We administered nicotine to achieve a steady-state concentration, using subcutaneously implanted minipumps, a technique that avoids the episodic hypoxic-ischemic episodes that accompany nicotine injections, and that also sidesteps the inherent problems of repeated handling stress and episodic withdrawal between injections” Slotkin et al., Neurotoxicology and Teratology 2002; 24:369-384.

“The measurement of substrate flux utilization is based on the novel use of the (ALZET) miniosmotic pump to supply a continuous infusion of one of three tracers…” Xu et al., The Journal of Biological Chemistry 2002;277(52):50237-50244.

 “Commercially available mini-osmotic pumps were pre-tested in vitro and proved to be a reliable method of slowly releasing the protein that was biologically active… The continuous presence of BMP-7 during the 2-4 weeks following surgery seemed to have attracted surrounding mesenchymal-like cells from the synovium into the defect area, and then transformed into chondrocytes.” Pecina et al. International Orthopaedics 2002; 26:131-136.

“Unlike injected nicotine, the infusion of nicotine via osmotic minipumps does not cause any overt signs of hypoxia/ischemia, such as blanching of the skin or cyanosis.” Xu et al., Brain Research 2002; 951:280-292.

“We switched to a 21-day minipumps paradigm using a dose that mimics serum antidepressant concentrations in humans because this regimen resulted in a more consistent and robust decrease in serotonin transporter levels in rats than what is observed with daily injections of serotonin reuptake inhibitors.” Weinshenker et al. 2002 Brain Research 946:239-246.

“However, the s.c. mini-osmotic pump delivery of recombinant leptin raised circulating leptin into the physiological range (Table 2). These data confirmed the effectiveness of the s.c. infusion of leptin at 0.1 mg/day in restoring serum leptin levels.” Zhang et al. Journal of Endocrinology 2002; 174:455-461.

“Continuous release of albuterol subcutaneously with a miniosmotic pump resulted in a sustained high plasma albuterol concentration throughout the entire experimental period.” Sartori et al., J Appl Physiol 2002;93:1875-1880.

"Utilizing continuous minipump administration enhances the knockdown to 63% of control." (p. 619) This compared with 40% by twice daily administration.  "The results of the present study confirm the utility of osmotic minipump administration of antisense oligonucleotides." (p. 621) Falk et al., Pharmacol Biochem Behav 2002;72:617-622.

“Mini-pumps were used to eliminate stress associated with multiple daily injections.” Akhter et al., Journal of Orthopaedic Research 2002;21:14-19.

“The implanted pumps offered an advantageous alternative to repeated injections. During drug delivery, no external connection was required, and rats were untethered and unrestrained, thereby minimizing animal handling stress” Zhang et al., Journal of Neurophysiology 2000;84:798-805.