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Pharmacokinetic estimations from microdialysis data

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Summary

Microdialysis has recently been adapted for sampling the extracellular fluid of various organs in order to measure drug concentrations, and the first clinical application has been published. My aim here is to provide simple rules about how to analyse pharmacokinetic data from such studies. The plotting of data on a time scale and the estimation of C (0) and slopes is not a trivial problem when multicompartmental models are assumed or sampling intervals are unequal. I have developed formulae and algorithms to solve the problem. A simple rule of thumb is given, suggesting when these formulae need to be applied. It is shown that the calculations of half-life and slopes is similar to standard methods for equal sample intervals and that calculation of AUC and clearance may be even more accurate for microdialysis data than for ordinary blood sampling, because of the time-integral character of the dialysis method. I have dealt with both zero-order and first-order kinetics.

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References

  • Ben-Nun J, Cooper RL, Cringle SJ, Constable IJ (1988) Ocular dialysis. A new technique forin vivo intraocular pharmacokinetic measurements. Arch Ophthalmol 106: 254–259

    CAS  PubMed  Google Scholar 

  • Brion N, Contrepois A, Carbon C (1983) De la pharmacocin6tique sérique à la pharmacocinétique extravasculaire des antibiotiques. Importance de la liaison protéines. Presse Med 12: 293–296

    CAS  PubMed  Google Scholar 

  • Brodie MS, Lee K, Fredholm BB, Ståhle L, Dunwiddie TV (1987) Central versus peripheral mediation of responses to adenosine receptor agonists: evidence against a central mode of action. Brain Res 415: 323–330

    Article  CAS  PubMed  Google Scholar 

  • Chisholm GD, Waterworth PM, Calnan JS, Garrod LP (1973) Concentration of antibacterial agents in interstitial tissue fluid. Br Med J 1: 569–573

    CAS  PubMed  Google Scholar 

  • Dubey RK, McAllister CB, Inoue M, Wilkinson GR (1989) Plasma protein binding and transport of diazepam across the blood-brain barrier. No evidence forin vivo enhanced dissociation. J Clin Invest 84: 1155–1159

    CAS  PubMed  Google Scholar 

  • Ferraro TN, Weyers P, Carrozza DP, Vogel WH (1990) Continuous monitoring of brain ethanol levels by intracerebral microdialysis. Alcohol 1: 129–132

    Google Scholar 

  • Gibaldi M, Levy G, Weintraub H (1974) Drug distribution and pharmacological effect. Clin Pharmacol Ther 12: 734–742

    Google Scholar 

  • Gibaldi M, Perrier D (1980) Pharmacokinetics, 2nd edn. Dekker, New York

    Google Scholar 

  • Gilbert RJ (1983) Studies of rabbits on the disposition and trypanocidal activity of the anti-trypanosomal drug, diminazene aceturate (Berenil). Br J Pharmacol 80: 133–139

    CAS  PubMed  Google Scholar 

  • Guyton AC (1963) A concept of negative interstitial pressure based on pressures in implanted perforated capsules. Circ Res 12: 399–414

    CAS  PubMed  Google Scholar 

  • Herrera AM, Scott DO, Lunte CE (1990) Microdialysis sampling for determination of plasma protein binding of drugs. Pharmaceut Res 7: 1077–1081

    Article  CAS  Google Scholar 

  • Hurd YL, Kehr J, Ungerstedt U (1988)In vivo microdialysis as a technique to monitor drug transport: correlation of extracellular cocaine levels and dopamine overflow in rat brain. J Neurochem 51: 1314–1316

    CAS  PubMed  Google Scholar 

  • Joly V, Pangon B, Brion N, Vallois J-M, Carbon C (1988) Enhancement of the therapeutic effect of cephalosporins in experimental carditis by altering their pharmacokinetics with diclofenac. J Pharmacol Exp Ther 246: 695–700

    CAS  PubMed  Google Scholar 

  • Mattie H, Hoogeterp JJ, Hermans J (1987) The relation between plasma and tissue concentrations of antibiotics. Description of a method. J Pharmacokin Biopharm 15: 191–202

    Article  CAS  Google Scholar 

  • Nye K, O'Neill P, Andrews JM, Wise R (1990) Pharmacokinetics and tissue penetration of cefprozil. J Antimicrob Ther 25: 831–835

    CAS  Google Scholar 

  • Rowland M, Tozer TN (1989) Clinical pharmacokinetics. Concepts and applications, 2nd edn. Lea & Febiger, Philadelphia

    Google Scholar 

  • Scott DO, Sorensen LR, Lunte CE (1990)In vivo microdialysis sampling coupled to liquid chromatography for the study of acetaminophen metabolism. J Chromatogr 506: 461–469

    Article  CAS  PubMed  Google Scholar 

  • Ståhle L (1991) Drug distrubtion studies with microdialysis: I. Tissue dependent difference in recovery between caffeine and theophylline. Life Sci 49: 1835–1842

    PubMed  Google Scholar 

  • Ståhle L, Segersvärd S, Ungerstedt U (1990) Estimation of theophylline in brain extracellular space by microdialysis: relation to behaviour. Eur J Pharmacol 185: 187–193

    Article  PubMed  Google Scholar 

  • Ståhle L, Arner P, Ungerstedt U (1991 a) Drug distribution studies with microdialysis. III. extracellular concentration of caffeine in adipose tissue in man. Life Sci 49: 1853–1858

    PubMed  Google Scholar 

  • Ståhle L, Segersvärd S, Ungerstedt U (1991 b) A comparison between three methods for estimation of extracellular concentrations of exogenous and endogenous compounds by microdialysis. J Pharmacol Meth 25: 41–52

    Article  Google Scholar 

  • Ståhle L, Segersvärd S, Ungerstedt U (1991 c) Drug distribution studies with microdialysis. II. distribution of caffeine and theophylline to blood, brain and other tissues in rats. Life Sciences 49: 1843–1852

    PubMed  Google Scholar 

  • Ungerstedt U (1984) Measurement of neurotransmitter release by intracranial dialysis. In: Marsden CA (ed) Measurement of neurotransmitter releasein vivo. Wiley, London, pp 81–105

    Google Scholar 

  • Ungerstedt U (1991) Introduction to intracerebral microdialysis. In: Robinson T, Justics J (eds) Methods in Neuroscience, Elsevier, Amsterdam, pp 3–22

    Google Scholar 

  • Wise R, Gillett AP, Cadge B, Durham SR, Baker S (1980) The influence of protein binding upon tissue fluid levels of sixβ-Alactam antibiotics. J Inf Dis 142: 77–82

    CAS  Google Scholar 

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Ståhle, L. Pharmacokinetic estimations from microdialysis data. Eur J Clin Pharmacol 43, 289–294 (1992). https://doi.org/10.1007/BF02333025

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