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The standard method for direct estimation of the brain delivery extent (K p,uu,brain ) is a cerebral microdialysis technique, which is used for continuous monitoring of unbound concentrations of the drug in the brain ISF and blood over the time via inserted probes into the brain parenchyma (90)

Patients with mild to moderate renal impairment generally do not require dose adjustment, but closer monitoring may be warranted, particularly for signs of gastrointestinal adverse effects that could lead to dehydration and worsening renal function

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J Pharmacol Exp Ther 245(3):873879 Navarro M, Pichini S, Farre M et al (2001) Usefulness of saliva for measurement of 3,4-methylenedioxymethamphetamine and its metabolites: correlation with plasma drug concentrations and effect of salivary pH