title: Therapeutic Drug Monitoring of Venlafaxine in an Everyday Clinical Setting: Analysis of Age, Sex and Dose Concentration Relationships.
abstract: Venlafaxine is a commonly used antidepressant agent. We aimed to provide detailed information on the associations between venlafaxine dose and concentrations of venlafaxine, by patient age and sex. From a therapeutic drug monitoring (TDM) database located at Odense University Hospital, Denmark, we identified all adults for whom the treating physician had requested clinical advice on the TDM result for venlafaxine between 2002 and 2012. We identified 1077 TDM samples of venlafaxine from 334 males and 743 females (median age 45 years), and the median daily dose was 225 mg. Median plasma concentration of venlafaxine and o-desmethylvenlafaxine (ODV) was 306 nmol/L and 861 nmol/L, respectively. The median dose-corrected serum level for venlafaxine was 1.49 nmol/L/mg., while the dose-corrected serum level of men and women were 1.21 nmol/L/mg and 1.60 nmol/L/mg, respectively. The dose-corrected sum of venlafaxine and ODV was 8.91 nmol/L/mg (IQR 6.56-12.26) versus 5.52 nmol/L/mg (IQR 4.16-7.52) for patients above 64 years and below the age of 65 years, respectively. Dose-corrected plasma concentrations of venlafaxine and ODV are increased to a clinically significant degree in patients above the age of 64, and initiation of venlafaxine therapy in the elderly should be made cautiously and supported by drug measurements.
authors.affiliation: Clinical Pharmacology and Pharmacy, University of Southern Denmark, Odense, Denmark.|Department of Clinical Biochemistry and Pharmacology, Odense University Hospital, Odense, Denmark.
authors.forename: Morten Rix
authors.initials: MR
authors.lastname: Hansen
authors.affiliation: Department of Clinical Biochemistry and Pharmacology, Odense University Hospital, Odense, Denmark.
authors.forename: Ida Berglund
authors.initials: IB
authors.lastname: Kuhlmann
authors.affiliation: Clinical Pharmacology and Pharmacy, University of Southern Denmark, Odense, Denmark.
authors.forename: Anton
authors.initials: A
authors.lastname: Pottegård
authors.affiliation: Department of Clinical Biochemistry and Pharmacology, Odense University Hospital, Odense, Denmark.|Department of Clinical Research, University of Southern Denmark, Odense, Denmark.
authors.forename: Per
authors.initials: P
authors.lastname: Damkier
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D018687:Antidepressive Agents, Second-Generation / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood* / Q000493:pharmacokinetics; D001711:Biotransformation; D016208:Databases, Factual; D003718:Denmark; D000069468:Desvenlafaxine Succinate / Q000097:blood; D004305:Dose-Response Relationship, Drug; D016903:Drug Monitoring / Q000379:methods*; D005260:Female; D006801:Humans; D008297:Male; D008745:Methylation; D008875:Middle Aged; D018579:Patient Selection; D018570:Risk Assessment; D012307:Risk Factors; D012737:Sex Factors; D000069470:Venlafaxine Hydrochloride / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood* / Q000493:pharmacokinetics
chemical_list: D018687:Antidepressive Agents, Second-Generation; D000069470:Venlafaxine Hydrochloride; D000069468:Desvenlafaxine Succinate