Microdialysis in awake macaque monkeys for central nervous system pharmacokinetics  

作　　者：Thibaud Thiollier Caisheng Wu Gregory Porras Erwan Bezard Qin Li Jinlan Zhang Hugues Contamin 

机构地区：[1]Cynbiose,Marcy l'Etoile [2]Université de Bordeaux, Institut des Maladies Neurodégénératives [3]CNRS, Institut des Maladies Neurodégénératives [4]Institute of Materia Medica, Chinese Academy of Medical Sciences [5]Motac Neuroscience [6]Institute of Laboratory Animal Sciences,China Academy of Medical Sciences

出　　处：《Animal Models and Experimental Medicine》2018年第4期314-321,共8页动物模型与实验医学（英文）

摘　　要：Background: The brain bioavailability of novel small molecules developed to address central nervous system disease is classically documented through ex vivo or in vivo analyses conducted in rodent models. Data acquired in rodent models are, however,not easily transferrable to human as the pharmacokinetic and pharmacodynamics profiles of the species are quite different.Methods: Using drugs selected for their differential transport across the blood-brain barrier, we here demonstrate the feasibility of brain microdialysis in normal vigil macaque monkey by measuring brain extracellular fluid bioavailability of carbamazepine, digoxin, oxycodone, and quinidine.Results: All drugs, but digoxin, were found in dialysate samples. Drugs that are substrate of P-glycoprotein show a difference of bioavailability or brain pharmacokinetic parameters between rodents and primates.Conclusion: Data suggest that brain microdialysis in vigil macaque monkey, the species of choice for classic pharmacokinetic/pharmacodynamics studies could help predicting human brain bioavailability of a small molecule depending on the protein involved in the efflux transport from the brain.Background: The brain bioavailability of novel small molecules developed to address central nervous system disease is classically documented through ex vivo or in vivo analyses conducted in rodent models. Data acquired in rodent models are, however,not easily transferrable to human as the pharmacokinetic and pharmacodynamics profiles of the species are quite different.Methods: Using drugs selected for their differential transport across the blood-brain barrier, we here demonstrate the feasibility of brain microdialysis in normal vigil macaque monkey by measuring brain extracellular fluid bioavailability of carbamazepine, digoxin, oxycodone, and quinidine.Results: All drugs, but digoxin, were found in dialysate samples. Drugs that are substrate of P-glycoprotein show a difference of bioavailability or brain pharmacokinetic parameters between rodents and primates.Conclusion: Data suggest that brain microdialysis in vigil macaque monkey, the species of choice for classic pharmacokinetic/pharmacodynamics studies could help predicting human brain bioavailability of a small molecule depending on the protein involved in the efflux transport from the brain.

关 键 词：AWAKE bioavailability blood BRAIN barrier BRAIN central nervous system crossing methods MICRODIALYSIS non-human PRIMATE PHARMACOKINETIC 

分 类 号：R[医药卫生]