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With a US Food and Drug Administration-labeled indication to treat attention-deficit/hyperactivity disorder (ADHD), the nonstimulant guanfacine has become the preferred α(2)-agonist for ADHD treatment. However, significant interindividual variability has been observed in response to guanfacine. Consequently, hypotheses of a contributing interaction with the ubiquitously expressed drug transporter, P-glycoprotein (P-gp), have arisen. We performed an in vitro study to determine if guanfacine is indeed a substrate of P-gp.

An in vitro evaluation of guanfacine as a substrate for P-glycoprotein