Determination of the Dermal Penetration of Esterom Components Using Microdialysis Sampling

McDonald, Sarah D.; Lunte, Craig E.

doi:10.1023/b:pham.0000003381.10208.8c

Cited by 13 publications

(15 citation statements)

References 14 publications

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“…mD methodology in the skin is easily combined with other methods such as laser doppler flowmetry, laser doppler perfusion imaging, transepidermal water loss (TEWL), colorimetry, high resolution ultrasound scanning, or scoring of itch and pain (49). The effect of barrier perturbation on cutaneous drug penetration (50) and the topical penetration of several components of topical analgesics has been demonstrated by mD (51).…”

Section: Dermal Microdialysismentioning

confidence: 99%

AAPS-FDA Workshop White Paper: Microdialysis Principles, Application and Regulatory Perspectives

et al. 2007

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Many decisions in drug development and medical practice are based on measuring blood concentrations of endogenous and exogenous molecules. Yet most biochemical and pharmacological events take place in the tissues. Also, most drugs with few notable exceptions exert their effects not within the bloodstream, but in defined target tissues into which drugs have to distribute from the central compartment. Assessing tissue drug chemistry has, thus, for long been viewed as a more rational way to provide clinically meaningful data rather than gaining information from blood samples. More specifically, it is often the extracellular (interstitial) tissue space that is most closely related to the site of action (biophase) of the drug. Currently microdialysis (microD) is the only tool available that explicitly provides data on the extracellular space. Although microD as a preclinical and clinical tool has been available for two decades, there is still uncertainty about the use of microD in drug research and development, both from a methodological and a regulatory point of view. In an attempt to reduce this uncertainty and to provide an overview of the principles and applications of microD in preclinical and clinical settings, an AAPS-FDA workshop took place in November 2005 in Nashville, TN, USA. Stakeholders from academia, industry and regulatory agencies presented their views on microD as a tool in drug research and development.

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Section: Dermal Microdialysismentioning

confidence: 99%

AAPS-FDA Workshop White Paper: Microdialysis Principles, Application and Regulatory Perspectives

et al. 2007

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“…27 The results in Figure 4D and Table 1 show that BA was detected in the muscle by NMR. Because HR-MAS NMR detects compounds in both intracellular and extracelluar domains, these results suggest that a significant fraction of the BA is localized in the intracellular space.…”

Section: Resultsmentioning

confidence: 85%

Concentration Profiling in Rat Tissue by High-Resolution Magic-Angle Spinning NMR Spectroscopy: Investigation of a Model Drug

et al. 2005

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The utility of high-resolution magic-angle spinning (HR-MAS) NMR for studying drug delivery in whole tissues was explored by dosing female Sprague-Dawley rats with topical or injectable benzoic acid (BA). In principle, HR-MAS NMR permits the detection of both intra-and extracellular compounds. This is an advantage over the previous detection of topically applied BA using microdialysis coupled to HPLC/UV as microdialysis samples only the extracellular space. Skin and muscle samples were analyzed by 1 H HR-MAS NMR, and BA levels were determined using an external standard solution added to the sample rotor. One to two percent of the BA topical dose was detected in the muscle, showing that BA penetrated through the dermal and subcutaneous layers. Since BA was not detected in the muscle in the microdialysis studies, the NMR spectra revealed the intracellular localization of BA. The amount of BA detected in muscle after subcutaneous injection correlated with the distance from the dosing site. Overall, the results suggest that HR-MAS NMR can distinguish differences in the local concentration of BA varying with tissue type, dosage method, and tissue proximity to the dosing site. The results illustrate the potential of this technique for quantitative analysis of drug delivery and distribution and the challenges to be addressed as the method is refined.Nuclear magnetic resonance (NMR) spectroscopy has played a significant role in the growth of metabonomics, an area of clinical research that aims to measure the total metabolic response of an organism to a stimulus such as a drug or toxicant or a physiological change such as a disease state. 1-3 The effects of the stimulus can be evaluated by measuring levels of specific analytes or through pattern recognition to permit the identification of a fingerprint of efficacy or toxicity. 1-3 Spectral analysis of the individual components that comprise the fingerprint reveals the identity of drug metabolites 4 and disease biomarkers. 5,6 The major advantages of NMR spectroscopy for metabonomics studies over other techniques, such as mass spectrometry, 7,8 are the universal nature of NMR detection, ease of quantitation, and the ability to analyze both biofluids and tissues to understand the local versus systemic effects of a stimulus. 9,10 Such an integrated metabonomics approach is an ongoing focus of this collaborative effort. Although NMR is generally less sensitive than other spectroscopic techniques, recent technological developments have reduced sample mass requirements and experiment times significantly. 11,12Tissue analysis by NMR spectroscopy is possible with a technique known as high-resolution magic-angle spinning (HR-MAS Another potential, but relatively unexplored, application of HR-MAS NMR tissue analysis is for drug delivery and distribution studies. Formulation is a critical part of the drug development process affecting the ADME (absorption, distribution, metabolism, and excretion) properties of a drug. While oral formulation is the preferred route for the ad...

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“…3 and 4), It would be possible to predict that 143 mM (about 5%) of cocaine contained in the cotton pledget would be diluted into less than 10 mM around the nasal epithelium after diffusion. This prediction is based on a report by McDonald and Lunte [27] that several micro molar order of cocaine was enough for complete anesthesia in the case of cutaneous nerve. In vivo mice study, we also observed quick recovery of OB field potential after inhibition on the olfactory epithelium exposed 5% cocaine (n = 3, unpublished data).…”

Section: A Local Anesthetic For the Otorhinolaryngeal Surgerymentioning

confidence: 99%

Suppression and recovery of voltage-gated currents after cocaine treatments of olfactory receptor cells

et al. 2013

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Determination of the Dermal Penetration of Esterom Components Using Microdialysis Sampling

Cited by 13 publications

References 14 publications

AAPS-FDA Workshop White Paper: Microdialysis Principles, Application and Regulatory Perspectives

AAPS-FDA Workshop White Paper: Microdialysis Principles, Application and Regulatory Perspectives

Concentration Profiling in Rat Tissue by High-Resolution Magic-Angle Spinning NMR Spectroscopy: Investigation of a Model Drug

Suppression and recovery of voltage-gated currents after cocaine treatments of olfactory receptor cells

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