PMID: 11902803Mar 21, 2002Paper

Distribution kinetics of solutes in the isolated in-situ perfused rat head using the multiple indicator dilution technique and a physiological two-barrier model

The Journal of Pharmacy and Pharmacology
K A FosterMichael S Roberts

Abstract

The purpose of this study was to determine the pharmacokinetics of [14C]diclofenac, [14C]salicylate and [3H]clonidine using a single pass rat head perfusion preparation. The head was perfused with 3-[N-morpholino] propane-sulfonic acid-buffered Ringer's solution. 99mTc-red blood cells and a drug were injected in a bolus into the internal carotid artery and collected from the posterior facial vein over 28 min. A two-barrier stochastic organ model was used to estimate the statistical moments of the solutes. Plasma, interstitial and cellular distribution volumes for the solutes ranged from 1.0 mL (diclofenac) to 1.6 mL (salicylate), 2.0 mL (diclofenac) to 4.2 mL (water) and 3.9 mL (salicylate) to 20.9 mL (diclofenac), respectively. A comparison of these volumes to water indicated some exclusion of the drugs from the interstitial space and salicylate from the cellular space. Permeability-surface area (PS) products calculated from plasma to interstitial fluid permeation clearances (CL(PI)) (range 0.02-0.40 mL s(-1)) and fractions of solute unbound in the perfusate were in the order: diclofenac > salicylate > clonidine > sucrose (from 41.8 to 0.10 mL s(-1)). The slow efflux of diclofenac, compared with clonidine and salicylate, may b...Continue Reading

References

Sep 1, 1979·Archives of Neurology·R E RamsayB J Wilder
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May 1, 1967·Journal of Applied Physiology·R K AndjusH A Sloviter
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Oct 1, 1994·British Journal of Clinical Pharmacology·S G OwenM S Roberts
Apr 6, 2000·Pharmaceutical Research·K A FosterM S Roberts

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Citations

Nov 26, 2010·Journal of Pharmacokinetics and Pharmacodynamics·Michael S Roberts
Dec 4, 2012·Journal of Psychiatry & Neuroscience : JPN·Sharon Miksys, Rachel F Tyndale
May 1, 2012·Drug Delivery and Translational Research·David F KatzMeng Kang

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