DOI: 10.1002/ame2.12046
Microdialysis in awake macaque monkeys for central nervous system pharmacokinetics
Thibaud Thiollier
Caisheng Wu
Gregory Porras
Erwan Bezard
Qin Li
Jinlan Zhang
Hugues Contamin
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.
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论文发表日期：2018-01-01
在线出版日期：2025-08-15（本平台首次上网日期，不代表文献的发表时间）
页数：8( 314-321 )
英文信息