Pharmacokinetic Parameters of Quinine in Healthy Subjects and in Patients with Uncomplicated Malaria in Nigeria: Analysis of Data using a Population Approach.
• Varied disposition imparts on the tolerance and safety of quinine, and thus constitutes a major limiting consideration for its dosing in uncomplicated malaria. Utilizing a population approach, the effect of body weight and infection status on disposition parameters of quinine were evaluated in Nig...
| Publicado en: | Current Therapeutic Research Vol. 91; pp. 33 - 39 |
|---|---|
| Autores principales: | , , , , , |
| Formato: | research tables/charts Journal Article |
| Publicado: |
Elsevier B.V.
2019
|
| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=140294811&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 140294811 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 0011393X KIH jtl: Current Therapeutic Research issn: 0011393X maglogo: N pubinfo: dt: 2019 vid: 91 pid: 467 pub: Elsevier B.V. place: New York, New York artinfo: ui: 140294811 140294811 140294811 10.1016/j.curtheres.2019.100567 140294811 ppf: 33 ppct: 6 formats: tig: atl: Pharmacokinetic Parameters of Quinine in Healthy Subjects and in Patients with Uncomplicated Malaria in Nigeria: Analysis of Data using a Population Approach. aug: au: Adehin, Ayorinde Igbinoba, Sharon I. Soyinka, Julius O. Onyeji, Cyprian O. Babalola, Chinedum P. Bolaji, Oluseye O. affil: Institute of Biomedical and Pharmaceutical Sciences, Guangdong University of Technology, Guangzhou, China sug: subj: Quinine Pharmacokinetics Malaria Metabolism Human Nigeria Quinine Administration and Dosage Patient Attitudes Chronic Disease Treatment Outcomes ab: • Varied disposition imparts on the tolerance and safety of quinine, and thus constitutes a major limiting consideration for its dosing in uncomplicated malaria. Utilizing a population approach, the effect of body weight and infection status on disposition parameters of quinine were evaluated in Nigerian subjects. • A reversal of infection-induced changes in volume of distribution and clearance after 48 h of chronic quinine administration was noted. • It is hypothesized that a downward review of quinine regimen post-48 h of chronic administration, in the event of complete parasitaemia clearance, might be a useful approach in enhancing tolerance and safety. The varied disposition of the antimalarial quinine partly explains its poor tolerance and toxicity in humans. Using a population approach, the disposition of quinine in healthy subjects and patients with acute uncomplicated symptomatic malaria from Nigeria was re-examined with a view to providing population-specific attributes. Concentration versus time profiles of quinine over 48 hours in healthy individuals, and over 7 days in malaria-infected patients, were stratified to reflect: concentration versus time data during the first 48 hours of quinine administration for healthy subjects and infected patients, concentration versus time data after 48 hours in infected patients, and all concentration versus time data available for healthy subjects and infected patients. Pharmacokinetic parameters were then estimated with a stochastic approximation expectation maximization algorithm. All datasets were fitted by a 1-compartment model with covariate contributions from body weight and infection status. The absorption rate constant, and volume of distribution and clearance were 1.72 h–1, 86.8 to 157.4 L, and 6.6 to 9.6 L/h, respectively. Infected patients experienced a 38% decrease in volume of distribution and a 31% decrease in clearance in the first 48 hours relative to healthy individuals. The contraction in volume of distribution and clearance diminished significantly after 48 hours of chronic quinine dosing in infected patients. The study findings suggest that clinical interventions aimed at enhancing the safety and tolerance of quinine might be achieved by a rational decrease in dose size and/or dosing interval, post-48 hours of chronic quinine administration, in malaria-infected patients. pubtype: Academic Journal doctype: research tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
|---|