Abstract:
AIM:The combination of ephedrine and caffeine has been used in herbal products for weight loss and athletic performance-enhancement, but the pharmacokinetic profiles of these compounds have not been well characterized. This study aimed to develop a mechanistic model describing ephedrine, norephedrine, and caffeine pharmacokinetics and their interactions in healthy subjects. METHODS:The pharmacokinetic model was developed based on the simultaneous modelling using plasma samples gathered from two clinical trials. The treatments consisted of single-doses of pharmaceutical caffeine and ephedrine, given alone or together, and an herbal formulation containing both caffeine and ephedrine. We used a mixed-effect statistical model and the program NONMEM to take account of intersubject variability. RESULTS:Three hundred and seventy-nine ephedrine, 352 norephedrine, 417 caffeine plasma concentrations and 40 ephedrine urine concentrations were obtained from 24 subjects. A one-compartment model with first-order absorption described the caffeine data. Caffeine clearance was 0.083 l min(-1) (CV 38%) and decreased to 0.038 l min(-1) in presence of oral contraceptive therapy, its volume of distribution was 38.6 l (CV 20%) and its absorption rate constant was 0.064 l min(-1) (CV 50%). A four-compartment model described the pharmocokinetics of ephedrine and norephedrine. Ephedrine was eliminated mostly renally, with a clearance of 0.34 l min(-1) (CV 11%), and a volume of distribution of 181 l (CV 19%). Nonlinearity in the conversion of ephedrine to norephedrine was observed. Different models showed that the simultaneous administration of caffeine, or the amount of caffeine in the absorption compartment, was associated with a slower rate of absorption of ephedrine. A 32% greater relative bioavailability of herbal compared with pharmaceutical ephedrine administration was observed. CONCLUSIONS:We describe a mechanistic model for ephedrine, norephedrine and caffeine pharmacokinetics and their interactions. The relative bioavailability of ephedrine differed between the herbal supplement compared with the pharmaceutical formulation. Concomitant ingestion of caffeine slowed the absorption rate of ephedrine, which is mainly related to the amount of the former in the absorption compartment. A saturable process appears to be involved in the metabolism of ephedrine to norephedrine.
journal_name
Br J Clin Pharmacoljournal_title
British journal of clinical pharmacologyauthors
Csajka C,Haller CA,Benowitz NL,Verotta Ddoi
10.1111/j.1365-2125.2005.02254.xkeywords:
subject
Has Abstractpub_date
2005-03-01 00:00:00pages
335-45issue
3eissn
0306-5251issn
1365-2125pii
BCP2254journal_volume
59pub_type
杂志文章,meta分析abstract:OBJECTIVE:To establish weight-based dose bands for commonly used oral medicines, given in liquid forms, for children in the UK that could be used for prescribing and administering accurate and safe drug doses. METHODS:A list of commonly prescribed, oral liquid medications was established from the medication dispensing...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/bcp.14698
更新日期:2020-12-10 00:00:00
abstract:WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT:Human pregnane X receptor (PXR/NR1I2) is a key regulator of cytochrome P450 3A4. To date, there are 198 reported SNPs for the human PXR/NR1I2 gene. Some of these SNPs are found to affect the inducing ability of PXR to CYP3A4. WHAT THIS STUDY ADDS:This study, for the first time,...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.2008.03344.x
更新日期:2009-02-01 00:00:00
abstract::1. Milk and plasma metronidazole and hydroxymetronidazole concentrations were measured in 12 breast-feeding patients following multiple doses of metronidazole (400 mg three times daily). All patients received metronidazole in combination with other broad spectrum antibiotics. 2. Plasma concentrations of both parent dr...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1988.tb03362.x
更新日期:1988-07-01 00:00:00
abstract:AIMS:The aim of this study was to investigate the effects of a single green tea (GT), administered concomitantly or 1 hour before nadolol intake on nadolol pharmacokinetics. METHODS:In a randomized 3-phase crossover study, 11 healthy volunteers received an oral administration of nadolol with, or 1 hour after preingest...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/bcp.14315
更新日期:2020-11-01 00:00:00
abstract::1 Two studies were carried out on acutely psychotic patients receiving chlorpromazine (100 mg) 8-hourly. 2 In the pilot study on five patients, plasma chlorpromazine concentrations fell over the course of 3 weeks of treatment and parallel changes were noted in the plasma half-life of antipyrine, salivation rate and ha...
journal_title:British journal of clinical pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1111/j.1365-2125.1975.tb01576.x
更新日期:1975-06-01 00:00:00
abstract:AIMS:The aim of the present study was to determine how the pharmacokinetics of meloxicam are affected by kidney dysfunction and consequently to define the appropriate dose for the use of meloxicam in patients with mild or moderate renal impairment. METHODS:Meloxicam was administered to subjects with mild (creatinine c...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1997.tb00030.x
更新日期:1997-01-01 00:00:00
abstract:AIMS:To test the hypothesis that inhibition of cytochrome P450 2D6 (CYP2D6) by quinidine increases the antitussive effect of dextromethorphan (DEX) in an induced cough model. METHODS:Twenty-two healthy extensive metaboliser phenotypes for CYP2D6 were studied according to a double-blind, randomised cross-over design af...
journal_title:British journal of clinical pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1046/j.1365-2125.1999.00029.x
更新日期:1999-09-01 00:00:00
abstract::1. Labetalol, a new drug combining alpha-and beta-adrenoceptor blocking properties, has been compared with placebo in a double-blind crossover study of a group of patients with mild to moderate essential hypertension (blood pressure 150/100 to 189/114 mmHg). 2. Labetalol and propranolol lowered blood pressure satisfac...
journal_title:British journal of clinical pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1111/j.1365-2125.1979.tb00898.x
更新日期:1979-01-01 00:00:00
abstract::1. The effects of heart failure due to chronic myocardial infarction on the responsiveness to injected angiotensin I and ACE inhibition by intravenous cilazapril (1 mg kg-1) were evaluated. 2. For this purpose one group of 17 rats with a 4-week old myocardial infarction was compared with a group of 10 sham operated ra...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1989.tb03478.x
更新日期:1989-01-01 00:00:00
abstract::Regulating drugs does not end when market access has been granted. Monitoring drugs over the life cycle has become state of the art, inherent to evolving legislation and societal need. Here, we explore how the drug label could move along in a changing playing-field and become a sustainable label for the future. A dial...
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abstract:AIMS:To characterize the pharmacokinetics of the dual 5alpha-reductase inhibitor GI198745 (dutasteride) to allow for more accurate predictions of GI198745 concentrations after different dosing schedules. METHODS:In this randomized, single-blind, parallel group study, 32 healthy male volunteers received single oral dos...
journal_title:British journal of clinical pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
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更新日期:1999-01-01 00:00:00
abstract:AIMS:To characterize potential mechanism-based inactivation (MBI) of major human drug-metabolizing cytochromes P450 (CYP) by monoamine oxidase (MAO) inhibitors, including the antitubercular drug isoniazid. METHODS:Human liver microsomal CYP1A2, CYP2C9, CYP2C19, CYP2D6 and CYP3A activities were investigated following c...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.2006.02627.x
更新日期:2006-05-01 00:00:00
abstract:AIM:The aim was to examine patients' stated preferences to persist with medicines and to explore the influence of psychosocial and sociocognitive factors. METHODS:Community-dwelling, hypertensive patients recruited from nine European countries were invited to complete a discrete choice experiment (DCE) with attributes...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/bcp.12971
更新日期:2016-08-01 00:00:00
abstract:AIMS:Breakthrough bleeding or even unwanted pregnancies have been reported in women during concomitant therapy with oral contraceptives and St John's wort extract. The aim of the present study was to investigate the effects of St John's wort extract on oral contraceptive therapy with respect to ovarian activity, breakt...
journal_title:British journal of clinical pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1046/j.1365-2125.2003.02005.x
更新日期:2003-12-01 00:00:00
abstract:AIMS:Within the new psychoactive substances (NPS) scenario, several hundred different molecules, mostly including synthetic cannabinoids and cathinones, have been identified so far. The aims of the paper were to: (i) identify the number of synthetic cathinones mentioned in a range of psychonaut, NPS-related, online sou...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/bcp.14132
更新日期:2020-03-01 00:00:00
abstract::1. We have investigated the effect of repeated s.c. Org 10172 (a low molecular weight heparinoid; Lomoparan) treatment (1000 anti-Xa units twice daily for 5 days) on antipyrine (500 mg orally) metabolism, and the effect of enzyme induction by pentobarbitone (100 mg for 12 days) on the pharmacokinetics and pharmacodyna...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1991.tb05608.x
更新日期:1991-07-01 00:00:00
abstract::1 This study was designed to compare in a double-blind randomized crossover trial, atenolol, labetalol, metoprolol and pindolol. Considerable differences in dose (atenolol 138 +/- 13 mg daily; labetalol 308 +/- 34 mg daily; metoprolol 234 +/- 22 mg daily; and pindolol 24 +/-2 mg daily were required to produce similar ...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1979.tb04774.x
更新日期:1979-04-01 00:00:00
abstract:AIMS:Hypertension is a common comorbidity of patients with COVID-19, SARS or HIV infection. Such patients are often concomitantly treated with antiviral and antihypertensive agents, including ritonavir and nifedipine. Since ritonavir is a strong inhibitor of CYP3A and nifedipine is mainly metabolized via CYP3A, the com...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/bcp.14684
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abstract::Coumarins are the mainstay of oral anticoagulation for the treatment and prophylaxis of thromboembolic disorders. They have a narrow therapeutic index and regular monitoring is therefore required to avoid serious adverse effects. There is wide interindividual variability in dosage requirements, which makes anticoagula...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章,评审
doi:10.1111/j.1365-2125.2006.02679.x
更新日期:2006-06-01 00:00:00
abstract::Methods of expressing the effects of beta-adrenoceptor blocking drugs on exercise heart rate have been evaluated using a standardised exercise test. In six normal subjects given atropine (0.04 mg/kg) on two separate occasions, the mean +/- s.e. mean exercise heart rate rose by 10.3 +/- 1.8 beats/min and by 11.0 +/- 1....
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1976.tb00348.x
更新日期:1976-12-01 00:00:00
abstract::1. The effects of chronic dosing with N-acetylcysteine (NAC), on nitrate-induced haemodynamic changes during the acute and chronic treatment of healthy volunteers with glyceryl trinitrate (GTN) patches (Transiderm nitro) has been investigated. 2. Seven volunteers were treated in a double-blind randomised crossover man...
journal_title:British journal of clinical pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1111/j.1365-2125.1989.tb03522.x
更新日期:1989-10-01 00:00:00
abstract::1. The pharmacokinetics of butorphanol were evaluated in 18 female volunteers with varying degrees of renal function following a single, 1 mg transnasal dose of butorphanol tartrate. The creatinine clearance (CLCR) values for subjects in the normal (NOR), moderately impaired (MI), and severely impaired (SI) groups wer...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1046/j.1365-2125.1996.03327.x
更新日期:1996-05-01 00:00:00
abstract::1 A treatment group comprising 635 hypertensive men (casual SBP greater than 175 or DBP greater than 115 twice) was compared with a reference group (n = 391 men; casual SBP greater than 175 or DBP greater than 115 only at screening). All men belonged to the same population sample of 7,455 men aged 47-54 yr. 2 The two ...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1979.tb04699.x
更新日期:1979-01-01 00:00:00
abstract::The mydriatic response to eyedrops of the anticholinergic drug tropicamide at very low concentration (0.01%) was studied in subjects with Alzheimer's disease (AD, n = 10) and multi-infarct dementia (MID, n = 10). There was no significant difference in pupillary response between the two groups. The test is unlikely to ...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1996.tb00194.x
更新日期:1996-03-01 00:00:00
abstract:AIMS:The purposes of this work were to: (1) compare pharmacokinetic (PK) parameters for hydroxycarbamide in children receiving their first dose (HCnew ) vs. those receiving chronic therapy (HCchronic ), (2) assess the external validity of a published PK dosing strategy, and (3) explore the accuracy of dosing strategies...
journal_title:British journal of clinical pharmacology
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1111/bcp.13426
更新日期:2018-07-01 00:00:00
abstract:AIMS:This study assessed the effects of the CYP3A inhibitors lopinavir/ritonavir (LPV/r) on the steady-state pharmacokinetics (PK) of aplaviroc (APL), a CYP3A4 substrate, in healthy subjects. METHODS:In Part 1, APL PK was determined in eight subjects who received a single oral 50-mg APL test dose with/without a single...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.2006.02661.x
更新日期:2006-09-01 00:00:00
abstract:AIM:Statins are inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase and are an important group of hypolipidaemic drugs, widely used in the treatment of hypercholesterolaemia and cardiovascular disease. Some studies have shown that statins are able to modulate inflammation and alveolar bone loss. METHODS:In o...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/bcp.12564
更新日期:2015-06-01 00:00:00
abstract:AIMS:The objective of this study is to develop a generic model for tacrolimus pharmacokinetics modelling using a meta-analysis approach, that could serve as a first step towards a prediction tool to inform pharmacokinetics-based optimal dosing of tacrolimus in different populations and indications. METHODS:A systemati...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章,meta分析
doi:10.1111/bcp.14110
更新日期:2019-12-01 00:00:00
abstract:AIM:Elevated serum creatinine (sCr) and low estimated glomerular filtration rate (eGFR) are associated with poor outcomes in patients with pulmonary arterial hypertension (PAH) whereas sildenafil treatment improves PAH outcomes. This post hoc analysis assessed the effect of sildenafil on kidney function and links with ...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1111/bcp.12616
更新日期:2015-08-01 00:00:00
abstract::Metabolomics is recognized as a powerful top-down system biological approach to understand genetic-environment-health paradigms paving new avenues to identify clinically relevant biomarkers. It is nowadays commonly used in clinical applications shedding new light on physiological regulatory processes of complex mammal...
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pub_type: 杂志文章,评审
doi:10.1111/j.1365-2125.2012.04216.x
更新日期:2013-03-01 00:00:00