title: Quinine as a potential tracer for medication adherence: A pharmacokinetic and pharmacodynamic assessment of quinine alone and in combination with oxycodone in humans.
abstract: Effective strategies to monitor pharmacotherapy adherence are necessary, and sensitive biological markers are lacking. This study examined a subtherapeutic dose of quinine as a potential adherence tracer. Primary aims included examination of the plasma and urinary pharmacokinetic profile of once-daily quinine; secondary aims assessed pharmacokinetic/pharmacodynamic interactions with oxycodone (a CYP3A and CYP2D substrate). Healthy, nondependent opioid users (n = 9) were enrolled in this within-subject, double-blind, placebo-controlled inpatient study. Participants received the following oral doses: day 1, oxycodone (30 mg); days 2-4, quinine (80 mg); day 5, quinine and oxycodone (2 hours postquinine). Blood and 24-hour urine samples were collected throughout the study, and pharmacodynamic outcomes were assessed during experimental sessions (days 1, 4, 5). Quinine displayed a plasma Tmax ∼2 hours and t1/2 ∼10 hours. Oxycodone and noroxycodone parameters (Tmax , Cmax , t1/2 ) were similar with or without quinine present, although drug exposure (AUC) was slightly greater when combined with quinine. No pharmacodynamic interactions were detected, and doses were safely tolerated. During washout, quinine urinary concentrations steadily declined (elimination t1/2 ∼16 hours), with a 94% decrease observed 72 hours postdose. Overall, low-dose quinine appears to be a good candidate for a medication additive to monitor adherence for detection of missed medication.
authors.affiliation: University of Kentucky College of Medicine, Department of Behavioral Science, Lexington, KY, USA.|University of Kentucky, Center on Drug and Alcohol Research, Lexington, KY, USA.
authors.forename: Shanna
authors.initials: S
authors.lastname: Babalonis
authors.affiliation: National Institute on Drug Abuse, Division of Pharmacotherapies and Medical Consequences, Rockville, MD, USA.
authors.forename: Aidan J
authors.initials: AJ
authors.lastname: Hampson
authors.affiliation: University of Kentucky College of Medicine, Department of Behavioral Science, Lexington, KY, USA.|University of Kentucky, Center on Drug and Alcohol Research, Lexington, KY, USA.|University of Kentucky College of Medicine, Department of Psychiatry, Lexington, KY, USA.
authors.forename: Michelle R
authors.initials: MR
authors.lastname: Lofwall
authors.affiliation: University of Kentucky, Center on Drug and Alcohol Research, Lexington, KY, USA.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Nuzzo
authors.affiliation: University of Kentucky College of Medicine, Department of Behavioral Science, Lexington, KY, USA.|University of Kentucky, Center on Drug and Alcohol Research, Lexington, KY, USA.|University of Kentucky College of Medicine, Department of Psychiatry, Lexington, KY, USA.|University of Kentucky College of Pharmacy, Department of Pharmaceutical Sciences, Lexington, KY, USA.|University of Kentucky College of Medicine, Department of Pharmacology, Lexington, KY, USA.
authors.forename: Sharon L
authors.initials: SL
authors.lastname: Walsh
mesh_terms: D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000097:blood / Q000652:urine; D001785:Blood Gas Monitoring, Transcutaneous; D001794:Blood Pressure / Q000187:drug effects; D004311:Double-Blind Method; D004347:Drug Interactions; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D055118:Medication Adherence; D008875:Middle Aged; D010098:Oxycodone / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D011680:Pupil / Q000187:drug effects; D011803:Quinine / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D056152:Respiratory Rate / Q000187:drug effects; D055815:Young Adult
chemical_list: D015415:Biomarkers; D011803:Quinine; D010098:Oxycodone
keywords: adherence; human; oxycodone; pharmacokinetic; quinine; tracer