Determination of in vivo steady-state unbound drug concentration in the brain interstitial fluid by microdialysis

doi:10.1016/0378-5173(92)90006-N

International Journal of Pharmaceutics

Volume 81, Issues 2–3, 31 March 1992, Pages 143-152

https://doi.org/10.1016/0378-5173(92)90006-N Get rights and content

Abstract

The in vivo unbound concentrations of [³H]water, caffeine and aminopyrine in the hippocampal interstitial fluid were directly determined by means of a brain microdialysis technique. The steady-state unbound concentration in the interstitial fluid (ISF) was determined from the dialysate concentration and the in vivo permeability rate constants of these compounds which were extrapolated from the in vitro permeability rate constant and from the effective dialysis coefficient of a reference compound such as antipyrine. The values of the unbound concentrations of [³H]water, caffeine and aminopyrine obtained by extrapolation were very close to those predicted from the plasma concentrations based on the assumption that the unbound concentration in the tissue interstitial fluid is the same as that in the plasma. Moreover, the damage due to implantation of transcranial-type microdialysis cannula was evaluated using [¹⁴C]sucrose as an extracellular marker. The average ISF/plasma ratios of [¹⁴C]sucrose estimated for the initial 30 min dialysis were 7% at l h and 3.7% at 48 h after implantation of the cannula, respectively, which correspond well with that (2.0–6.1%) estimated from the blood-brain barrier permeability rate constant reported previously. Therefore, we conclude that the microdialysis technique using the reference method for determination of the unbound concentration of ISF is a useful procedure for the reliable evaluation of the in vivo unbound concentration in brain ISF and that the blood-brain barrier is not significantly damaged by cannula implantation.

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Determination of in vivo steady-state unbound drug concentration in the brain interstitial fluid by microdialysis

Abstract

J. Pharmacol. Methods

Prog. Neurobiol.

Life Sci.

J. Pharmacol. Methods

J. Pharmacol. Methods

Brain microdialysis

J. Neurochem.

Cellular reactions to implantation of a microdialysis tube in the rat hippocampus

Acta Neuropathol.

Elevation of the extracellular concentrations of glutamate and aspartate in rat hippocampus during transient cerebral ischemia monitored by intracerebral microdialysis

J. Neurochem.

Determination of brain interstitial concentrations by microdialysis

J. Neurochem.

Blood-brain barrier transport of valproic acid

J. Neurochem.

Muscle microdialysis as a model study to relate the drug concentration in tissue interstitial fluid and dialysate

J. Pharmacobio-Dyn.

An application of microdialysis to drug tissue distribution study: In vivo evidence for free-ligand hypothesis and tissue binding of β-lactam antibiotics in interstitial fluids

J. Pharmacobio-Dyn.

Plasma binding and transport of diazepam across the blood-brain barrier. No evidence for in vivo enhanced dissociation

J. Clin. Invest.

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Mass transfer in brain dialysis devices — a new method for the estimation of extracellular amino acids concentration

J. Neurosci. Methods

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