Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.6.3.44 (P-glycoprotein)
 13,344 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Although the interaction between selective serotonin reuptake inhibitors (SSRIs) and other drugs is important in the treatment of depression, there have been few studies of SSRIs concerning transporter-mediated interactions in humans. The objective of this study was to evaluate the in vivo effects of commonly used SSRIs on the pharmacokinetics of fexofenadine, a P-glycoprotein substrate.Twelve healthy volunteers (3 females and 9 males) were enrolled in this study. Each subject received a 60-mg dose of fexofenadine orally at baseline. Afterward, they were randomly assigned to receive 3 treatments with a 60-mg dose of fexofenadine after a 7-day treatment with fluvoxamine (50 mg/d), paroxetine (20 mg/d), or sertraline (50 mg/d), with 2-week intervals between the agents.Fluvoxamine pretreatment significantly increased the maximum plasma concentration, the area under the concentration time curves, and the 24-hour urinary fexofenadine excretion by 66% (P = 0.004), 78% (P = 0.029), and 78% (P < 0.001), respectively, without prolonging its elimination half-life. Paroxetine extended the elimination half-life of fexofenadine by 45% (P = 0.042), and it increased the 24-hour urinary fexofenadine excretion by 55% (P = 0.002). Sertraline did not alter any of the pharmacokinetic parameters of fexofenadine.This is the first report of the different effects of 3 commonly used SSRIs on fexofenadine pharmacokinetics in humans. Our 7-day, repeated-dose clinical study in healthy volunteers indicates that fluvoxamine and paroxetine, but not sertraline, may impact the patient exposure to fexofenadine, which is likely the result of P-glycoprotein inhibition in the small intestine and/or the liver.
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PMID:Different effects of the selective serotonin reuptake inhibitors fluvoxamine, paroxetine, and sertraline on the pharmacokinetics of fexofenadine in healthy volunteers. 2236 58

Drug combination therapy is sometimes used in clinical situations. CYP has been intensely studied numerous times ; thus, its pharmacokinetic interactions have been predicted to some extent. Basically, a drug interaction is defined as competitive inhibition of an enzyme by two drugs. We are concerned that fluvoxamine may have a drug interaction with paroxetine. Flu-voxamine inhibits CYPlA2 and CYP2C9 activity, and paroxetine inhibits CYP2D6 activity. However, recently, new drug targets have been identified, such as P-glycoprotein, a drug transporter. Fluvoxamine and paroxetine inhibit not only CYP but also P-glycoprotein. Additionally, there is an increased risk of upper gastrointestinal tract bleeding with the combination of a SSRI and NSAIDs. There are also individual differences in the pharmacokinetics of drugs due to genetic factors and individual differences in drug receptors, which have not yet been investigated for fluvoxamine or paroxetine. Obtaining clinical diagnoses of drug interactions is necessary in all patients.
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PMID:[The Drug Interaction that Psychiatrists Should be Careful about]. 3062 May 11