Prediction of clinical response based on pharmacokinetic/pharmacodynamic models of 5-hydroxytryptamine reuptake inhibitors in mice

TY - JOUR

T1 - Prediction of clinical response based on pharmacokinetic/pharmacodynamic models of 5-hydroxytryptamine reuptake inhibitors in mice

AU - Kreilgaard, Mads

AU - Smith, D G

AU - Brennum, L T

AU - Sánchez, C

PY - 2008/9

Y1 - 2008/9

N2 - Bridging the gap between preclinical research and clinical trials is vital for drug development. Predicting clinically relevant steady-state drug concentrations (Css) in serum from preclinical animal models may facilitate this transition. Here we used a pharmacokinetic/pharmacodynamic (PK/PD) modelling approach to evaluate the predictive validity of 5-hydroxytryptamine (5-HT; serotonin) transporter (SERT) occupancy and 5-hydroxytryptophan (5-HTP)-potentiated behavioral syndrome induced by 5-HT reuptake inhibitor (SRI) antidepressants in mice.

AB - Bridging the gap between preclinical research and clinical trials is vital for drug development. Predicting clinically relevant steady-state drug concentrations (Css) in serum from preclinical animal models may facilitate this transition. Here we used a pharmacokinetic/pharmacodynamic (PK/PD) modelling approach to evaluate the predictive validity of 5-hydroxytryptamine (5-HT; serotonin) transporter (SERT) occupancy and 5-hydroxytryptophan (5-HTP)-potentiated behavioral syndrome induced by 5-HT reuptake inhibitor (SRI) antidepressants in mice.

KW - Animals

KW - Citalopram

KW - Male

KW - Mice

KW - Models, Biological

KW - Paroxetine

KW - Serotonin

KW - Serotonin Uptake Inhibitors

KW - Sertraline

U2 - 10.1038/bjp.2008.243

DO - 10.1038/bjp.2008.243

M3 - Journal article

C2 - 18552871

SN - 0007-1188

VL - 155

SP - 276

EP - 284

JO - British Journal of Pharmacology

JF - British Journal of Pharmacology

IS - 2

ER -