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Postauricular hypodermic injection to treat inner ear disorders: experimental feasibility study using magnetic resonance imaging and pharmacokinetic comparison

Published online by Cambridge University Press:  14 February 2013

J Li
Affiliation:
Department of Otolaryngology, Head and Neck Surgery, People's Hospital, Peking University, Beijing, China
L Yu*
Affiliation:
Department of Otolaryngology, Head and Neck Surgery, People's Hospital, Peking University, Beijing, China
R Xia
Affiliation:
Department of Radiology and Molecular Imaging Center, West China Hospital, Sichuan University, Chengdu City, China
F Gao
Affiliation:
Department of Radiology and Molecular Imaging Center, West China Hospital, Sichuan University, Chengdu City, China
W Luo
Affiliation:
Department of Otolaryngology, Head and Neck Surgery, The Second Affiliated Hospital, Chongqing University of Medical Sciences, China
Y Jing
Affiliation:
Department of Otolaryngology, Head and Neck Surgery, People's Hospital, Peking University, Beijing, China
*
Address for correspondence: Dr Lisheng Yu, 11 Xizhimen South Street, Xicheng District, Beijing City, 100044, China Fax: +86 10 68318386 E-mail: [email protected]

Abstract

Background:

To investigate the feasibility of postauricular hypodermic injection for treating inner ear disorders, we compared perilymph pharmacokinetics for postauricular versus intravenous injection, using magnetic resonance imaging, in an animal model.

Methods:

Twelve albino guinea pigs were divided randomly into two groups and administered gadopentetate dimeglumine via either a postauricular or an intravenous bolus injection. A 7.0 Tesla magnetic resonance imaging system was used to assess the signal intensities of gadolinium-enhanced images of the cochlea, as a biomarker for changes in gadopentetate dimeglumine concentration in the perilymph. Pharmacokinetic parameters were calculated based on these signal intensity values.

Results:

Guinea pigs receiving postauricular injection showed longer times to peak signal intensity, longer elimination half-life, longer mean residence time and a greater area under the signal–time curve (from pre-injection to the last time point) (p < 0.05).

Conclusion:

Postauricular injection shows potential as an efficient drug delivery route for the treatment of inner ear disorders.

Type
Main Articles
Copyright
Copyright © JLO (1984) Limited 2013

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References

1Shi, X. Resident macrophages in the cochlear blood-labyrinth barrier and their renewal via migration of bone-marrow-derived cells. Cell Tissue Res 2010;342:2130CrossRefGoogle ScholarPubMed
2Borkholder, DA, Zhu, X, Hyatt, BT, Archilla, AS, Livingston, WJ 3rd, Frisina, RD. Murine intracochlear drug delivery: reducing concentration gradients within the cochlea. Hear Res 2010;268:211CrossRefGoogle ScholarPubMed
3Yang, XQ, Yu, LS, Ma, X. Postaurical injection of compound betamethasone to treat the intractable low-frequency sensorineural hearing loss [in Chinese]. Chin J Otorhinolaryngol Head Neck Surg 2007:42:814–16Google ScholarPubMed
4Lin, YJ, Yu, LS. Determination of dexamethasone in the cochlear tissue after postaurical and intramuscular injection [in Chinese]. Chin Arch Otolaryngol Head Neck Surg 2009;7:381384Google Scholar
5Counter, SA, Zou, J, Bjelke, B, Klason, T. 3D MRI of the in vivo vestibule-cochlea labyrinth during Gd-DTPA-BMA uptake. Neuroreport 2003;14:1707–12CrossRefGoogle Scholar
6Zhang, Y, Huo, M, Zhou, J, Xie, S. PKSolver: an add-in program for pharmacokinetic and pharmacodynamic data analysis in Microsoft Excel. Comput Methods Programs Biomed 2010;99:306–14CrossRefGoogle ScholarPubMed
7Zou, J, Pyykkö, I, Counter, SA, Klason, T, Bretlau, P, Bjelke, B. In vivo observation of dynamic perilymph formation using 4.7 T MRI with gadolinium as a tracer. Acta Otolaryngol 2003;123:910–15CrossRefGoogle ScholarPubMed
8Mynatt, R, Hale, SA, Gill, RM, Plontke, SK, Salt, AN. Demonstration of a longitudinal concentration gradient along scala tympani by sequential sampling of perilymph from the cochlear apex. J Assoc Res Otolaryngol 2006;7:182–93CrossRefGoogle ScholarPubMed
9Hamid, M, Trune, D. Issues, indications, and controversies regarding intratympanic steroid perfusion. Curr Opin Otolaryngol Head Neck Surg 2008;16:434–40CrossRefGoogle ScholarPubMed
10Juhn, SK. Barrier systems in the inner ear. Acta Otolaryngol Suppl 1988;458:7983CrossRefGoogle ScholarPubMed
11Moskowitz, D, Lee, KJ, Smith, HW. Steroid use in idiopathic sudden sensorineural hearing loss. Laryngoscope 1984;94:664–6CrossRefGoogle ScholarPubMed
12Goycoolea, MV. Clinical aspects of round window membrane permeability under normal and pathological conditions. Acta Otolaryngol 2001;121:437–47CrossRefGoogle ScholarPubMed
13Mikulec, AA, Hartsock, JJ, Salt, AN. Permeability of the round window membrane is influenced by the composition of applied drug solutions and by common surgical procedures. Otol Neurotol 2008;29:1020–6CrossRefGoogle ScholarPubMed
14Yoshioka, M, Naganawa, S, Sone, M, Nakata, S, Teranishi, M, Nakashima, T. Individual differences in the permeability of the round window: evaluating the movement of intratympanic gadolinium into the inner ear. Otol Neurotol 2009;30:645–8CrossRefGoogle ScholarPubMed
15Alzamil, KS, Linthicum, FH Jr.Extraneous round window membranes and plugs: possible effect on intratympanic therapy. Ann Otol Rhinol Laryngol 2000;109:30–2CrossRefGoogle ScholarPubMed
16Swan, EE, Mescher, MJ, Sewell, WF, Tao, SL, Borenstein, JT. Inner ear drug delivery for auditory applications. Adv Drug Deliv Rev 2008;14:1583–99CrossRefGoogle Scholar
17Plontke, SK, Mikulec, AA, Salt, AN. Rapid clearance of methylprednisolone after intratympanic application in humans. Otol Neurotol 2008;29:732–3CrossRefGoogle ScholarPubMed
18Salt, AN, Plontke, SK. Principles of local drug delivery to the inner ear. Audiol Neurotol 2009;14:350–60CrossRefGoogle ScholarPubMed
19Jing, YY, Yu, LS, Li, XQ. Compound betameth pharmacokinetics in plasma of guinea pig after postaurieal injection [in Chinese]. J Audiol Speech Pathol 2009;17:354357Google Scholar
20Zou, J, Zhang, W, Poe, D, Qin, J, Fornara, A, Zhang, Y et al. MRI manifestation of novel superparamagnetic iron oxide nanoparticles in the rat inner ear. Nanomedicine (Lond) 2010;5:739–54CrossRefGoogle ScholarPubMed
21Counter, SA, Bjelke, B, Borg, E, Klason, T, Chen, Z, Duan, ML. Magnetic resonance imaging of the membranous labyrinth during in vivo gadolinium (Gd-DTPA-BMA) uptake in the normal and lesioned cochlea. Neuroreport 2000;11:3979–83CrossRefGoogle ScholarPubMed
22Plontke, SK, Salt, AN. Simulation of application strategies for local drug delivery to the inner ear. ORL J Otorhinolaryngol Relat Spec 2006;68:386–92CrossRefGoogle ScholarPubMed
23Lyford-Pike, S, Vogelheim, C, Chu, E, Della Santina, CC, Carey, JP. Gentamicin is primarily localized in vestibular type I hair cells after intratympanic administration. J Assoc Res Otolaryngol 2007;8:497508CrossRefGoogle ScholarPubMed
24Lattuada, L, Gabellini, M. Straightforward synthesis of a novel maleimide-DTPA bifunctional chelating agent. Synth Commun 2005;35:2409–13CrossRefGoogle Scholar
25Takumida, M, Anniko, M. Localization of endotoxin in the inner ear following inoculation into the middle ear. Acta Otolaryngol 2004;124:772–7CrossRefGoogle ScholarPubMed