Subcutaneous microdialysis in rats correlates with carbamazepine concentrations in plasma and brain.
Microdialysis simplifies the measurement of pharmacokinetics in pharmacodynamically relevant tissues. Microdialysis permits serial measurements of unbound drug concentration. The objective of the present work was to study rats to correlate plasma carbamazepine pharmacokinetics with subcutaneous and brain tissues. Microdialysis probes were inserted into the jugular vein, the brain, and subcutaneous tissue in Sprague-Dawley rats. After receiving single doses of carbamazepine, 12 mg/kg i.p., pharmacokinetic sampling occurred simultaneously from three microdialysis sites. Microdialysis sampled unbound carbamazepine and carbamazepine-10, 11-epoxide concentrations. Concentrations measured in brain, subcutaneous, and plasma correlated with each other. Except where differences were anticipated, pharmacokinetic parameters, including half-life and time to maximum concentration, were the same regardless of measurement site. The present study suggests microdialysis may allow pharmacokinetic measurements in peripheral physiological spaces that are surrogates for the pharmacologically relevant tissue.
Graumlich
J F
JF
Departments of Biomedical and Therapeutic Sciences and Medicine, University of Illinois College of Medicine at Peoria, Peoria, IL, USA. jfg@uic.edu
McLaughlin
R G
RG
Birkhahn
D
D
Shah
N
N
Burk
A
A
Jobe
P C
PC
Dailey
J W
JW
D000818:Animals; D000927:Anticonvulsants / Q000097:blood* / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001921:Brain / Q000378:metabolism*; D002220:Carbamazepine / Q000031:analogs & derivatives / Q000097:blood* / Q000493:pharmacokinetics*; D005260:Female; D017551:Microdialysis / Q000379:methods; D009994:Osmolar Concentration; D051381:Rats; D017207:Rats, Sprague-Dawley; D012867:Skin / Q000378:metabolism
D000927:Anticonvulsants; D002220:Carbamazepine; C012227:carbamazepine epoxide