caa a22 4500 477128319 CHVBK 20180405111656.0 cr unu---uuuuu 170330e19970201xx s 000 0 eng 10.1023/A:1012080106490 doi (NATIONALLICENCE)springer-10.1023/A:1012080106490 Drug Equilibration Across the Blood—Brain Barrier-Pharmacokinetic Considerations Based on the Microdialysis Method [Elektronische Daten] [Margareta Hammarlund-Udenaes, Lennart Paalzow, Elizabeth de Lange] Purpose. The purpose of the study was to investigate the influence of different rates of transport into and out of the brain, including passive and active transport, on unbound brain concentrations and profile in relation to the blood concentration profile. Special emphasis is put on hydrophilic drugs. Methods. Simulations were performed with a model including one body compartment and one brain compartment, with linear or saturable transport into and out of the brain. Comparisons were made with experimental results from microdialysis (MD) studies. Results. Three features were evident when combining the MD results: 1) equilibration across the blood-brain barrier (BBB) is rapid, 2) half-life is similar in brain and blood for most drugs, and 3) unbound brain concentrations seldom reach the level of unbound blood concentrations. A low concentration ratio brain:blood is not mainly caused by a low influx, but rather by different influx and efflux clearances. Active transport out of the brain can explain the results, but also active transport into the brain under certain conditions. A small volume of distribution in brain vs. that in the rest of the body contributes to a rapid equilibration and similar half-lives. Conclusions. Assumptions of slow equilibration of hydrophilic drugs and similar unbound concentrations across the BBB at steady state are contradicted. The results are more in line with recent findings on the presence of P-glycoprotein and other transport mechanisms at the BBB. Non-passive transport across the BBB seems to be the case for almost all drugs studies with MD so far. Plenum Publishing Corporation, 1997 microdialysis nationallicence blood-brain barrier transport nationallicence pharmacokinetics nationallicence drug equilibration nationallicence Hammarlund-Udenaes Margareta aut Paalzow Lennart aut de Lange Elizabeth aut Pharmaceutical Research Kluwer Academic Publishers-Plenum Publishers 14/2(1997-02-01), 128-134 0724-8741 14:2<128 1997 14 11095 https://doi.org/10.1023/A:1012080106490 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1023/A:1012080106490 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Hammarlund-Udenaes Margareta aut NATIONALLICENCE 700 1- Paalzow Lennart aut NATIONALLICENCE 700 1- de Lange Elizabeth aut NATIONALLICENCE 773 0- Pharmaceutical Research Kluwer Academic Publishers-Plenum Publishers 14/2(1997-02-01), 128-134 0724-8741 14:2<128 1997 14 11095 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer