Subcutaneous administration of nimodipine improves bioavailability in rabbits

Laslo, A.M.; Eastwood, James D.; Urquhart, Brad L.; Lee, Ting‐Yim; Freeman, Dave

doi:10.1016/j.jneumeth.2004.04.030

Cited by 13 publications

(14 citation statements)

References 16 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These studies also proved the effectiveness of subcutaneous nimodipine pellets in providing dose-dependent levels of nimodipine in both plasma and brain 14,20 . Because subcutaneous pellets obviate daily drug injections, they reduce the neurophysiological trauma that can be detrimental to behavioral testing 14 , and eliminate the intake and bioavailability issues associated with oral dosing regimens 21 .…”

Section: Resultsmentioning

confidence: 99%

Nimodipine and Acceleration of Functional Recovery of the Facial Nerve After Crush Injury

Lindsay

Heaton²,

Edwards³

et al. 2010

Arch Facial Plast Surg

View full text Add to dashboard Cite

Objective To establish whether nimodipine, a calcium channel blocker, accelerates or otherwise improves functional recovery of whisking after facial nerve crush injury in the rat. Methods Thirty rats underwent exposure of the left main trunk of the facial nerve followed by a standard crush injury, and subsequent quantitative facial movement testing. Animals were randomized into an experimental group (n=15) and a control group (n=15 each). Four days prior to facial nerve manipulation, experimental animals underwent subcutaneous implantation of a nimodipine-secreting pellet. All animals were tested pre-operatively and on post-crush days 2, 8–17, 20, 22, 24, and 31, using a validated, quantitative whisking kinematics apparatus. Whisks were analyzed for amplitude, velocity, and acceleration. Results Animals receiving nimodipine demonstrated significantly better whisking on days 9, 11–13, and 20 compared with control animals (p<.05). Overall, the nimodipine-treated animals showed earlier recovery as compared to the untreated animals. Conclusions We demonstrate that nimodipine improves recovery of whisking after facial nerve crush. This finding corroborates the semi-quantitative findings of others, and provides complete whisking kinematic data on its effects. Given the low side effect profile of nimodipine, there may be clinical implications in its administration in patients experiencing facial nerve injury.

show abstract

Section: Resultsmentioning

confidence: 99%

Nimodipine and Acceleration of Functional Recovery of the Facial Nerve After Crush Injury

Lindsay

Heaton²,

Edwards³

et al. 2010

Arch Facial Plast Surg

View full text Add to dashboard Cite

show abstract

“…Subcutaneous isradipine (2.5 mg/kg for 7 days) antagonizes hypoxia-induced hippocampal damage and memory impairments in rats (Barhwal et al , 2009) and subcutaneous doses of 3 mg/kg for 7 days protects dopaminergic neurons in an in vivo mouse model of Parkinson’s disease (Chan et al , 2007). Subcutaneous nimodipine (5–15 mg/kg/day) maintains plasma levels at or above therapeutic concentrations for treating vasospasm in a rabbit model of subarachnoid hemorrhage, whereas oral administration fails to do so (Laslo et al , 2004). Our results showed that isradipine concentrations in the range of 50–100 nM may be useful in protecting MC65 cells (Figure 1).…”

Section: Discussionmentioning

confidence: 99%

L-type voltage-gated calcium channel blockade with isradipine as a therapeutic strategy for Alzheimer's disease

Anekonda

Quinn

Harris

et al. 2011

Neurobiology of Disease

137

112

View full text Add to dashboard Cite

There is strong evidence that intracellular calcium dysregulation plays an important pathological role in Alzheimer’s disease, and specifically that beta amyloid may induce increases in intracellular calcium and lead to neuronal cell dysfunction and death. Here we investigated the feasibility of modifying Alzheimer’s pathology with the L-type voltage-gated calcium channel blockers verapamil, diltiazem, isradipine and nimodipine. All four compounds protected MC65 neuroblastoma cells from amyloid beta protein precursor C-terminal fragment (APP CTF)-induced neurotoxicity. Isradipine was the most potent blocker, preventing APP CTF neurotoxicity at nanomolar concentrations. Intracellular beta amyloid expression was associated with increased expression of Cav 1.2 calcium channels and increased intracellular calcium influx from the extracellular space. Despite the cytoprotection afforded by calcium channel blockers, amyloid beta oligomer formation was not suppressed. The mechanism of cell death in MC65 cells is appeared to be caspase-3 independent. With the goal of determining if there is sufficient experimental support to move forward with animal trials of isradipine, we determined its bioavailability in the triple transgenic mouse model of AD. Subcutaneous implatation of carrier-bound isradipine (3 µg/g/day) for 60 days resulted in nanomolar concentrations in both the plasma and brain. Taken together, our in vitro results support the theory that calcium blockers exert protective effects downstream of the effects of beta amyloid. Isradipine’s neuroprotective effect at concentrations that are clinically relevant and achievable in vitro and in vivo suggests that this particular calcium blocking agent may have therapeutic value in the treatment of Alzheimer’s disease.

show abstract

“…The primary goal of this work was to develop a nimodipine formulation using a better-tolerated drug delivery system to deliver nimodipine. Various approaches or drug delivery systems of formulating nimodipine, including emulsions (Zhang et al, 2004), slow-release pellets (Perez-Trepichio & Jones, 1996), subcutaneous administration (Laslo et al, 2004), intranasal administration (Zhang & Jiang, 2005), and liposome (Schlossmann et al, 1985) have been reported. Among the drug delivery systems, liposomes represent a mature, versatile technology with considerable potential for entrapment of both lipophilic and hydrophilic drugs (Vemuri & Rhodes, 1995).…”

Section: Introductionmentioning

confidence: 99%

Preparation, Characterization, and Pharmacokinetics of Sterically Stabilized Nimodipine-Containing Liposomes

Yang

Zhu

Zheng

et al. 2006

Drug Development and Industrial Pharmacy

View full text Add to dashboard Cite

Nimodipine is a dihydropyridine calcium antagonist used in clinical trials in the treatment of ischemic damage in subarachnoid hemorrhage and commercially available as nimotop intravenous infusion solution and tablets. However, due to its poor solubility in water, intravenous administration depends on the use of the dehydrated alcohol to achieve a clinically relevant concentrated infusion solution while the low bioavailability of the nimotop tablets were far away from content. We have prepared a well-characterized novel lyophilized liposome-based nimodipine formulation that is sterile and easy-to-use. Of the several formulations examined, nimodipine-liposomes composed of ePC/CHOL 20:3 and co-surfactant poloxamer 188/sodium deoxycholate/ePC/3:0.3:5 were chosen for further studies. This composition was found to give more stable liposomes than other formulations. It gave 89.9% entrapment efficiency and particle size of 200 nm after lyophilization. The pharmacokinetic parameters following orally and intravenously administration to New Zealand rabbits were determined and compared with those of commercial nimodipine formulations. Encapsulation of nimodipine in liposomes produced marked differences over those of commercial preparations with an increased C(max), prolonged elimination half-life, and an increased value for AUC. The obtained values for mean residence time (MRT) indicated that nimodipine remains longer for liposomal formulation. Thus an optimum i.v. liposome formulation for nimodipine can be developed for an alternative to the commercial nimodipine preparations.

show abstract

Subcutaneous administration of nimodipine improves bioavailability in rabbits

Cited by 13 publications

References 16 publications

Nimodipine and Acceleration of Functional Recovery of the Facial Nerve After Crush Injury

Nimodipine and Acceleration of Functional Recovery of the Facial Nerve After Crush Injury

L-type voltage-gated calcium channel blockade with isradipine as a therapeutic strategy for Alzheimer's disease

Preparation, Characterization, and Pharmacokinetics of Sterically Stabilized Nimodipine-Containing Liposomes

Contact Info

Product

Resources

About