Objective <p>The purpose of this study is to analyze the impact of the blood–brain barrier (BBB) and blood-cerebrospinal fluid barrier (BCSFB) transport characteristics of drugs on their intracerebral distribution in male cynomolgus monkeys.</p> Methods <p>Steady-state concentrations of 15 drugs (13 drugs and 2 compounds) transported by passive diffusion or via solute carrier (SLC) and/or ATP-binding cassette (ABC) transporters were measured in the frontal cortex interstitial fluid (ISF), lateral ventricular cerebrospinal fluid (CSF) and lumbar CSF of monkey brain by means of microdialysis and lumbar puncture methods. The values of brain ISF (or CSF)/plasma unbound concentration ratio (K_p,uu) were calculated to quantify the intracerebral distribution characteristics.</p> Results <p>The K_{p,uu,ISF,cortex} values of substrates of P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP)were much lower than unity. The ISF concentration of these drugs were increased by the co-administration of elacridar, suggesting active efflux of these drugs at the BBB. Contrary to expectations, some of P-gp substrates were efficiently distributed into the brain with K_{p,uu,ISF,cortex} &gt; 2. The lateral ventricular CSF concentrations of drugs tended to be higher than the ISF concentrations, while the lumbar CSF concentrations were comparable to the ISF concentrations.</p> Conclusion <p>The results of this study suggest that the intracerebral distribution of the test drugs from the blood in the monkey brain should consider the contribution of influx transporters as well as efflux transporters. In addition, the lumbar CSF concentrations of the test drugs appear to be a useful surrogate marker of the ISF concentrations.</p>