Abstract
Purpose. To investigate the performance of two alternative retrodialysis recovery methods and to describe the influence of different recoveries on the reliability in estimating unbound extracellular concentrations of morphine.
Methods. Unbound concentrations of morphine in striatum and in blood were determined by microdialysis after a 10 min i.v. infusion in freely moving rats. In vivo recovery of morphine was determined by morphine itself, retrodialysis by drug, and by the calibrator nalorphine, retrodialysis by calibrator.
Results. The low calibrator recovery in striatum (8.6%) resulted in large variability in the estimation of unbound extracellular concentrations when retrodialysis by calibrator was used. In blood, where the recovery was higher (36%), the variability was smaller. Also, when retrodialysis by drug was used, the variability remained low. This difference is caused by the propagation of errors in the way retrodialysis recovery is determined. Therefore, calibrator recovery values ≥ 20% are preferable in concentration estimations using retrodialysis by calibrator.
Conclusions. When no time-dependent change in recovery is observed, retrodialysis by drug determined before the systemic administration is the best method. The calibrator is valuable as a quality control during the experiment.
Similar content being viewed by others
REFERENCES
H. Benveniste and P. C. Huttemeier. Microdialysis—theory and 1pplication. Prog. Neurobiol. 35:195–215 (1990).
P. F. Morrison, P. M. Bungay, J. K. Hsiao, B. A. Ball, I. N. Mefford, and R. L. Dedrick. Quantitative microdialysis: analysis of transients and application to pharmacokinetics in brain. J. Neurochem. 57:103–19 (1991).
P. Lönnroth, P. A. Jansson, and U. Smith. A microdialysis method allowing characterization of intercellular water space in humans. Am. J. Physiol. 253:E228–31 (1987).
L. Ståhle. The use of microdialysis in pharmacokinetics and pharmacodynamics. In T. E. Robinson and J. B. Justice (eds.), Microdialysis in the Neurosciences, Vol. 7, Elsevier Science Publishers B.V., Amsterdam, 1991, pp. 155–174.
C. I. Larsson. The use of an “internal standard” for control of the recovery in microdialysis. Life Sci. 49:PL73–8 (1991).
L. Ståhle. (I) Drug distribution studies with microdialysis: I. Tissue dependent difference in recovery between caffeine and theophylline. Life Sci. 49:1835–42 (1991).
S. L. Wong, Y. Wang, and R. J. Sawchuk. Analysis of zidovudine distribution to specific regions in rabbit brain using microdialysis. Pharm. Res. 9:332–8 (1992).
Y. Wang, S. L. Wong, and R. J. Sawchuk. Microdialysis calibration using retrodialysis and zero-net flux: application to a study of the distribution of zidovudine to rabbit cerebrospinal fluid and thalamus. Pharm. Res. 10:1411–9 (1993).
B. Moghaddam and B. S. Bunney. Ionic composition of microdialysis perfusing solution alters the pharmacological responsiveness and basal outflow of striatal dopamine. J. Neurochem. 53:652–4 (1989).
E. C. M. De Lange, M. R. Bouw, J. W. Mandema, M. Danhof, A. G. De Boer, and D. D. Breimer. Application of intracerebral microdialysis to study regional distribution kinetics of drugs in rat brain. Br. J. Pharmacol. 116:2538–44 (1995).
H. Benveniste, A. J. Hansen, and N. S. Ottosen. Determination of brain interstitial concentrations by microdialysis. J. Neurochem. 52:1741–50 (1989).
N. Lindefors, G. Amberg, and U. Ungerstedt. Intracerebral microdialysis: I. Experimental studies of diffusion kinetics. J. Pharmacol. Methods 22:141–56 (1989).
P. M. Bungay, P. F. Morrison, and R. L. Dedrick. Steady-state theory for quantitative microdialysis of solutes and water in vivo and in vitro. Life Sci. 46:105–19 (1990).
R. Xie and M. Hammarlund-Udenaes. Blood-brain barrier equilibration of codeine in rats studied with microdialysis. Pharm. Res. 15:568–73 (1998).
P. Sjöberg, I. M. Olofsson, and T. Lundqvist. Validation of different microdialysis methods for the determination of unbound steady-state concentrations of theophylline in blood and brain tissue. Pharm. Res. 9:1592–8 (1992).
Y. Wang and D. F. Welty. The simultaneous estimation of the influx and efflux blood-brain barrier permeabilities of gabapentin using a microdialysis-pharmacokinetic approach. Pharm. Res. 13:398–403 (1996).
M. Gårdmark, M. Ekblom, R. Bouw, and M. Hammarlund-Udenaes. Quantification of effect delay and acute tolerance development to morphine in the rat. J. Pharmacol. Exp. Ther. 267:1061–7 (1993).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Bouw, M.R., Hammarlund-Udenaes, M. Methodological Aspects of the Use of a Calibrator in In Vivo Microdialysis–Further Development of the Retrodialysis Method. Pharm Res 15, 1673–1679 (1998). https://doi.org/10.1023/A:1011992125204
Issue Date:
DOI: https://doi.org/10.1023/A:1011992125204