In Vivo Real-Time Simultaneous Examination of Drug Kinetics at Two Separate Locations Using Boron-Doped Diamond Microelectrodes

Abstract

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.

Analysis of Pharmacokinetics in the Cochlea of the Inner Ear

“…These findings suggest that methylcobalamin possibly reaches compartments other than perilymph and exerts a pharmacological effect. Hanawa et al, 2020). Methylcobalamin (10 mg/kg) was injected into the left external jugular vein at 30 min (filled arrowhead) after the onset of the recording.…”

“…These results indicate that our microsensing system can simultaneously monitor pharmacokinetics and pharmacodynamics in a live cochlea. Additionally, we constructed a different system, composed of two BDD microelectrodes, and examined methylcobalamin concentration in separate targets ( Hanawa et al, 2020 ). This cobalamin derivative is often administered to patients with SNHL ( Wang et al, 2013 ).…”

“…The currents in perilymph (blue) and in the muscle (red) were simultaneously measured with two BDD microelectrodes. The concentration scales on the vertical axis are derived from in vitro calibration for each electrode (for details, see Hanawa et al, 2020 ). Methylcobalamin (10 mg/kg) was injected into the left external jugular vein at 30 min (filled arrowhead) after the onset of the recording.…”

“…The limit of detection (LOD) for each microsensor is indicated as a blue (muscle) or red (cochlea) dotted line. Adapted from Hanawa et al (2020) with permission. Copyright (2020) American Chemical Society.…”

Application of Boron-doped Diamond Electrodes: Focusing on the Electrochemical Reduction of Carbon Dioxide

“…increasing year by year and several review articles and books on diamond-based electrodes have now been published. [1][2][3][4][5][6][7][8][9][10] For the last 20 years, our research group have reported not only fundamental studies on BDD, but also on several novel electrochemical applications such as electrochemical sensors (including biomedical), [11][12][13][14][15][16][17][18] electrochemiluminescence, [19][20][21][22] and electrochemical organic synthesis. [23][24][25] These applications are due to the unique properties of BDD electrodes, and they could not be achieved using conventional electrodes.…”