Methylcobalamin, which is used for the clinical treatment of patients with neuropathy, can have an impact on the sensorineural components associated with the cochlea, and it is possible that the auditory threshold in a certain population of patients with deafness may be recovered. Nonetheless, it remains uncertain whether the action site of methylcobalamin is localized inside or outside the cochlea and which cellular or tissue element is targeted by the drug. In the present work, we developed a method to realize in vivo real-time simultaneous examination of the drug kinetics in two separate locations using boron-doped diamond microelectrodes. First, the analytical performance of methylcobalamin was studied and the measurement protocol was optimized in vitro. Then, the optimized protocol was applied to carry out realtime measurements inside the cochlea and the leg muscle in live guinea pigs while systemically administering methylcobalamin. The results showed that the methylcobalamin concentration in the cochlea was below the limit of detection for the microelectrodes or the drug did not reach the cochlea, whereas the compound clearly reached the leg muscle.
Vancomycin is a glycopeptide antibiotic that kills bacteria by blocking the construction of the cell wall and used to treat different bacterial diseases including meningitis and methicillin-resistant Staphylococcus aureus infections.Because this antibiotic can sometimes induce renal failure and hearing loss, the plasma concentration is monitored to adjust the dose applied to individual patients. In this study, we show a rapid and simple procedure with an electrochemical approach. The sensor we used consisted of a boron-doped diamond electrode, which elicits more stable reaction than classical materials such as carbon and gold. With this sensor we examined guinea-pig plasma containing vancomycin at different concentrations. The procedure we developed allowed us to complete a series of measurement in 35 sec. Time necessary for all the processes including a sample's pretreatment did not exceed 10 min. The sensor detected the drug concentration of 1 to 50 µM, which falls into the range of the therapeutic window. Moreover, we found that the sensor was repeatedly usable for the measurement with minimal impairment of the sensitivity. The methodology described here may contribute to not only advances in personalized medicine but also reduction of the cost for therapeutic drug monitoring.
Molecular-targeted anticancer drugs elicit less toxicity than conventional reagents. Yet, patients often suffer from severe adverse effects. A reason is 'fixed dosage' administration of the drug to all the patients regardless of their body size and complications; because of this strategy, the plasma concentration seems to exceed the therapeutic window occasionally. Although frequent measurement of the drug level at a clinical site is a solution, currently available methods such as mass spectrometry are time and cost consuming. To overcome these shortcomings, in this study, we developed a procedure with an electrochemical sensor composed of a conductive diamond, which yields more stable reactions than conventional materials. When guinea-pig plasma mixed with pazopanib, a multi-kinase inhibitor, was tested, the sensor detected a clinically relevant concentration of 3 to 300 µM. Time and sample amount necessary for each series of the measurement was <1 min and 100 µL, respectively. The sensor was repeatedly usable with minimal impairment of the sensitivity, saving the cost for the assay. This rapid and easily-handed method may enable therapeutic drug monitoring and accelerate tailored medicine for cancer.
YIA
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