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 sub-therapeutic 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, non-dependent 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 hrs post-quinine). Blood and 24-hr 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 hrs and t1/2 ∼10 hrs. 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 hrs), with a 94% decrease observed 72 hrs post-dose. Overall, low-dose quinine appears to be a good candidate for a medication additive to monitor adherence for detection of missed medication.

A Pharmacokinetic Study Examining Acetazolamide as a Novel Adherence Marker for Clinical Trials

“…The data reported here represent data taken during the phase in which ACZ was evaluated (the first 9 days). Between days 9–15 quinine was evaluated using the same subjects and essentially the same experimental design; the results of that study phase, along with details of the study design, the subjects, and sample analyses have been published 15 . What follows are protocol, analytical and methods details which are particular to the ACZ study, notably due to changes made as a result of an interim analysis of samples and data from Subjects 1–4.…”

“…An array of physiological, subjective and observer-rated measures were collected throughout each test session as previously described 15 to capture the pharmacodynamic effects of oxycodone, acetazolamide and their combination. Side effects were also queried daily using a checklist that contained acetazolamide specific side effects from the package label (ringing in the ears, blurry vision, numbness in hands or feet, tingling sensations in hands or feet, numb or tingling sensation in mouth and metallic taste in mouth) and oxycodone effects.…”

“…The data examining quinine using similar methods has been published elsewhere 15 . In addition, the interaction of ACZ on PK/PD outcomes was assessed with a model test medication.…”

Oral fluid cocaine and benzoylecgonine concentrations following controlled intravenous cocaine administration

“…Cocaine was administered alone on Day 1, in combination with oral acetazolamide on Day 5, and with oral quinine on Day 10. The study’s primary aims were to evaluate potential pharmacodynamic and pharmacokinetic interactions between cocaine and acetazolamide and quinine, as they are being considered as medication compliance markers for cocaine use disorder treatment pharmacotherapies, similar to a study performed with oxycodone and quinine by Babalonis et al [27]. …”

Synthesis of Quinopyrroloquinoline Derivatives under Catalyst-Free Conditions

“…现在对于风湿 关节炎的治疗, 也有一定效果. 再如奎宁(图 1) [3] , 是一 种天然的生物碱, 最初分离于茜草科植物金鸡纳树及其 同属植物的树皮中. 该药物能与疟原虫的 DNA 结合, 形成复合物, 抑制其 DNA 的复制和 RNA 的转录, 广泛 用于治疗疟疾.…”