Biomedical subjects

Stefan K R Plontke

Publications and source records attributed to Stefan K R Plontke.

4 recordsLinked to original sources

PubMed2005

Local inner-ear drug delivery and pharmacokinetics.

Several drugs that are applied directly to the inner ear are in widespread clinical use for the treatment of inner-ear disorders. Many new substances and drug delivery systems specific to the inner ear are under development and in some cases are being evaluated in animal experiments and in clinical studies. However, the pharmacokinetics of drugs in the inner ear is not well defined and the field is plagued by technical problems in obtaining pure samples of the inner-ear fluids for analysis. Nevertheless, a basic understanding of the mechanisms of drug dispersal in the inner ear has emerged, which facilitates the design and interpretation of future pharmacokinetic studies.

Animals↗

PubMed2003

Quantitative interpretation of corticosteroid pharmacokinetics in inner fluids using computer simulations.

The delivery of drugs to the inner ear by applying them directly onto the round window membrane is a promising way to treat human inner ear disorders. To further develop this strategy, and to design controlled clinical trials, additional preclinical studies are necessary. It is especially important to derive the time course and total dose for the various target regions within the inner ear. Since direct pharmacokinetic measurements in the human cochlea are not possible, simulations provide a valuable tool for the interpretation and planning of animal studies, for evaluating changes of application protocols and drug delivery systems, and for extrapolating the results from animal studies to the human. The present study has analyzed two previously published data sets in which concentration time courses of corticosteroids in the cochlear fluids were reported. Drug movements were simulated with a finite element computer model of the inner ear fluids. The time course of corticosteroid pharmacokinetics could be approximated for each study by consideration of the specific experimental paradigm. Although the experimental studies reported considerably different drug levels in the fluid samples taken from the cochlea, these differences were largely explained by considering the experimental design of the respective studies. After correction for experimental differences, the calculated perilymph levels of drug were within a factor of two of each other. The simulations demonstrated that an important factor controlling the drug level achieved is the time the drug solution remains in the middle ear. It can be concluded that small differences in delivery protocols may cause large variations in the drug levels achieved in the inner ear fluids.

Adrenal Cortex Hormones↗

PubMed2002

Analysis of gentamicin kinetics in fluids of the inner ear with round window administration.

HYPOTHESIS: That a theoretical basis for quantifying drug distribution in the inner ear with local applications can be established. BACKGROUND: As methods of local drug delivery to the inner ear gain wider clinical acceptance it becomes important to establish how drugs are distributed in the ear as a function of time and for different delivery methods. METHODS: The time course of gentamicin concentration in the inner ear fluids was simulated with a program that considered general pharmacokinetic principles and incorporated inner ear dimensions and drug dispersal processes, including diffusion, clearance, and intercompartmental exchange. RESULTS: Cochlear fluid space dimensions of the chinchilla were derived from three-dimensional magnetic resonance images and were incorporated into the simulator. The published time course of gentamicin in vestibular perilymph of chinchillas was closely approximated by the adjustment of parameters defining round window membrane permeability, clearance, and interscala exchange. To simulate the time course, it was necessary for drug entry into the vestibule to be dominated by interscala exchange rather than longitudinal spread through the helicotrema. The effects of different round window delivery methods were also calculated. Perilymph drug levels and spatial distribution in the ear were shown to be markedly influenced by the time the applied drug remained in the middle ear. CONCLUSION: The development of local inner ear drug application strategies requires consideration of inner ear pharmacokinetic characteristics, delivery methods, and therapeutic range of the drug.

Animals↗

PubMed2002

Transtympanic endoscopy for drug delivery to the inner ear using a new microendoscope.

Anatomic variations of the round window (RW) niche found in approximately 33% of human temporal bones may account for some ofthe problems associated with local drug delivery to the inner car. A microendoscope with a total outer diameter of 1.2 mm was developed in particular for easy visualization and of drug delivery to the RW niche. It incorporated a thin fiber optic, a working/laser channel (0.3 mm) and an irrigation/suction channel (0.27 mm). When compared to a common 30 degree lens optic, with the microendoscope a greater area of the round window niche could be overseen. In addition, the endoscope could be advanced directly upon the surface of the RW membrane (RWM). The microendoscope may be used for evaluation of the anatomy of the RW niche prior to the placement of local drug delivery systems, for application of drugs directly onto the surface of the RWM or to verify the correct placement of inner ear drug delivery systems.

Administration, Topical↗