Jf. Graumlich et al., Subcutaneous microdialysis in rats correlates with carbamazepine concentrations in plasma and brain, EPILEPSY R, 40(1), 2000, pp. 25-32
Microdialysis simplifies the measurement of pharmacokinetics in pharmacodyn
amically relevant tissues. Microdialysis permits serial measurements of unb
ound drug concentration. The objective of the present work was to study rat
s to correlate plasma carbamazepine pharmacokinetics with subcutaneous and
brain tissues. Microdialysis probes were inserted into the jugular vein, th
e brain, and subcutaneous tissue in Sprague-Dawley rats. After receiving si
ngle doses of carbamazepine, 12 mg/kg i.p., pharmacokinetic sampling occurr
ed simultaneously from three microdialysis sites. Microdialysis sampled unb
ound carbamazepine and carbamazepine-10,11-epoxide concentrations. Concentr
ations measured in brain, subcutaneous, and plasma correlated with each oth
er. Except where differences were anticipated, pharmacokinetic parameters,
including half-life and time to maximum concentration, were the same regard
less of measurement site. The present study suggests microdialysis may allo
w pharmacokinetic measurements in peripheral physiological spaces that are
surrogates for the pharmacologically relevant tissue. (C) 2000 Elsevier Sci
ence B.V. All rights reserved.