Abstract:
OBJECTIVE:As quinine is mainly metabolised by human liver CYP3A4 and grapefruit juice inhibits CYP3A4, the effect of grapefruit juice on the pharmacokinetics of quinine following a single oral dose of 600 mg quinine sulphate was investigated. METHODS:The study was carried out in ten healthy volunteers using a randomised cross-over design. Subjects were studied on three occasions, with a washout period of 2 weeks. During each period, subjects received a pretreatment of 200 ml orange juice (control), full-strength grapefruit juice or half-strength grapefruit juice twice daily for 5 days. On day 6, the subjects were given a single oral dose of 600 mg quinine sulphate with 200 ml of one of the juices. Plasma and urine samples for measurement of quinine and its major metabolite, 3-hydroxyquinine, were collected over a 48-h period and analysed by means of a high-performance liquid chromatography method. RESULTS:The intake of grapefruit juice did not significantly alter the oral pharmacokinetics of quinine. There were no significant differences among the three treatment periods with regard to pharmacokinetic parameters of quinine, including the peak plasma drug concentration (Cmax), the time to reach Cmax (tmax), the terminal elimination half-life (t1/2), the area under the concentration-time curve and the apparent oral clearance. The pharmacokinetics of the 3-hydroxyquinine metabolite were slightly changed when volunteers received grapefruit juice. The mean Cmax of the metabolite (0.25+/-0.09 mg l(-1), mean +/- SD) while subjects received full-strength grapefruit juice was significantly less than during the control period (0.31+/-0.06 mg l(-1), P < 0.05) and during the intake of half-strength grapefruit juice (0.31+/-0.07 mg l(-1), P < 0.05). CONCLUSION:These results suggest that there is no significant interaction between the parent compound quinine and grapefruit juice, so it is not necessary to advise patients against ingesting grapefruit juice at the same time that they take quinine. Since quinine is a low clearance drug with a relatively high oral bioavailability, and is primarily metabolised by human liver CYP3A4, the lack of effect of grapefruit juice on quinine pharmacokinetics supports the view that the site of CYP inhibition by grapefruit juice is mainly in the gut.
journal_name
Eur J Clin Pharmacoljournal_title
European journal of clinical pharmacologyauthors
Ho PC,Chalcroft SC,Coville PF,Wanwimolruk Sdoi
10.1007/s002280050646subject
Has Abstractpub_date
1999-07-01 00:00:00pages
393-8issue
5eissn
0031-6970issn
1432-1041journal_volume
55pub_type
临床试验,杂志文章,随机对照试验abstract::The effect of a new dopamine receptor stimulating agent, piribedil (ET 495), was studied in 10 patients with Parkinson's syndrome, who had had no or a poor response to previous L-DOPA treatment, or had displayed marked side effects during L-DOPA administration. Piribedil produced significant improvement of the functio...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00567119
更新日期:1975-04-04 00:00:00
abstract:OBJECTIVE:Databases of subjects receiving antidepressants provide evidence on the use of drugs in typical patients and settings under real-world conditions. This study analysed a general practice database to estimate the prevalence of antidepressant drug use, describe the use of these compounds by gender and age and es...
journal_title:European journal of clinical pharmacology
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journal_title:European journal of clinical pharmacology
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abstract:PURPOSE:Aflibercept, a fully humanized vascular endothelial growth factor (VEGF)-targeted agent, has emerged as an effective therapy in the treatment of various solid tumors. We carried out an up-to-date meta-analysis to determine the risk of fatal adverse events (FAEs) in cancer patients treated with aflibercept. MET...
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abstract:PURPOSE:To gain insight into the experiences and handling of adverse drug reactions (ADRs) by the staffs of public primary healthcare (PHC) clinics in Eastern Cape Province, South Africa, as well as their perceptions of related adherence challenges in the treatment and follow-up of human immunodeficiency virus (HIV)-po...
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journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00637499
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journal_title:European journal of clinical pharmacology
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abstract:OBJECTIVE:To determine the possible interaction between the antihypertensive agent cicletanine and the hypoglycaemic drug tolbutamide. METHODS:Time-courses of glycaemia and serum immunoreactive insulin (IRI) were followed in 10 healthy subjects after two tolbutamide infusions in each volunteer; initially alone and 9 d...
journal_title:European journal of clinical pharmacology
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journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
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journal_title:European journal of clinical pharmacology
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journal_title:European journal of clinical pharmacology
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journal_title:European journal of clinical pharmacology
pub_type: 临床试验,杂志文章
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journal_title:European journal of clinical pharmacology
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journal_title:European journal of clinical pharmacology
pub_type: 临床试验,杂志文章
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journal_title:European journal of clinical pharmacology
pub_type: 临床试验,杂志文章
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pub_type: 临床试验,杂志文章
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journal_title:European journal of clinical pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
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journal_title:European journal of clinical pharmacology
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journal_title:European journal of clinical pharmacology
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journal_title:European journal of clinical pharmacology
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