Prediction of antiepileptic drug efficacy: the use of intracerebral microdialysis to monitor biophase concentrations.
Biophase concentrations of antiepileptic drugs can differ significantly from pharmacokinetics in plasma. A crucial determinant in the disposition of antiepileptic drugs to the brain is represented by the blood-brain barrier. There is growing evidence that this barrier can alter the availability of antiepileptic drugs at the target site. The permeability of the blood-brain barrier becomes particularly relevant in epileptic conditions and in drug refractory situations. In vivo, intracerebral microdialysis is a valuable technique to determine biophase drug concentrations as it enables investigation of antiepileptic drug transport and distribution in the brain as a function of time. The present review illustrates that intracerebral microdialysis is an indispensable tool for the assessment of the pharmacokinetics of antiepileptic drugs. In addition, we demonstrate how microdialysis data can be used in conjunction with mechanism-based pharmacokinetic/pharmacodynamic modeling for dose selection and optimization of the therapeutic regimen for novel compounds.
Clinckers
Ralph
R
Vrije Universiteit Brussel (VUB), Pharmaceutical Institute, Research Group Experimental Pharmacology, Department of Pharmaceutical Chemistry and Drug Analysis (labo FASC), Laarbeeklaan 103, Building G, 1090 Brussels, Belgium. Ralph.Clinckers@vub.ac.be
Smolders
Ilse
I
Vermoesen
Katia
K
Michotte
Yvette
Y
Danhof
Meindert
M
Voskuyl
Rob
R
Della Pasqua
Oscar
O
D000818:Animals; D000927:Anticonvulsants / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001692:Biological Transport; D001812:Blood-Brain Barrier / Q000378:metabolism; D001921:Brain / Q000378:metabolism; D004827:Epilepsy / Q000188:drug therapy*; D006801:Humans; D017551:Microdialysis / Q000379:methods*; D008954:Models, Biological; D013997:Time Factors; D014018:Tissue Distribution
D000927:Anticonvulsants