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 combination of ritonavir and nifedipine can potentially cause drug-drug interactions. This study provides guidance on nifedipine treatment during and after coadministration with ritonavir-containing regimens, using a physiologically based pharmacokinetic/pharmacodynamic (PBPK/PD) analysis. METHODS:The PBPK/PD models for 3 formations of nifedipine were developed based on the Simcyp nifedipine model and the models were verified using published data. The effects of ritonavir on nifedipine exposure and systolic blood pressure (SBP) were assessed for instant-release, sustained-release and controlled-release formulations in patients. Various nifedipine regimens were investigated when coadministered with or without ritonavir. RESULTS:PBPK/PD models for 3 formulations of nifedipine were successfully established. The predicted maximum concentration (Cmax ), area under plasma concentration-time curve (AUC), maximum reduction in SBP and area under effect-time curve were all within 0.5-2.0-fold of the observed data. Model simulations showed that the inhibitory effect of ritonavir on CYP3A4 increased the Cmax of nifedipine 17.92-48.85-fold and the AUC 63.30-84.01-fold at steady state and decreased the SBP by >40 mmHg. Thus, the combination of nifedipine and ritonavir could lead to severe hypotension. CONCLUSION:Ritonavir significantly affects the pharmacokinetics and antihypertensive effect of nifedipine. It is not recommended for patients to take nifedipine- and ritonavir-containing regimens simultaneously.
journal_name
Br J Clin Pharmacoljournal_title
British journal of clinical pharmacologyauthors
Niu W,Li S,Jin S,Lin X,Zhang M,Cai W,Jiao Z,Xiang Xdoi
10.1111/bcp.14684subject
Has Abstractpub_date
2020-12-02 00:00:00eissn
0306-5251issn
1365-2125pub_type
杂志文章abstract:AIMS:To assess the effect of the calcitonin gene-related peptide (CGRP) receptor antagonist, telcagepant, on the haemodynamic response to sublingual nitroglycerin (NTG). METHODS:Twenty-two healthy male volunteers participated in a randomized, placebo-controlled, double-blind, two-period, crossover study. Subjects rece...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章,随机对照试验
doi:10.1111/j.1365-2125.2010.03869.x
更新日期:2011-05-01 00:00:00
abstract::Nine young and 12 elderly healthy volunteers received nisoldipine 10 mg once a day for 7 days. Plasma nisoldipine concentrations were measured on Day 1 and on Day 7. Higher plasma drug concentrations were observed in the elderly group than in the young group with the values for AUC being approximately doubled in the e...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1991.tb05547.x
更新日期:1991-03-01 00:00:00
abstract::1 We have given fifteen healthy volunteers single doses of racemic (+/-)-propranolol orally (40 mg) and intravenously (5-10 mg) to find out how large the variation was of the ratio between (-)- and (+)-propranolol plasma levels in relation to that of total levels of propranolol and 4-hydroxypropranolol. 2 Total propra...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1982.tb04937.x
更新日期:1982-07-01 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::Three calcium antagonists, diltiazem, flunarizine and verapamil stimulated human sperm motility in vitro. Among them, diltiazem induced the largest amplitude of motility increase. The concentration-response curve of diltiazem was similar in shape to those of calcium chelators. EGTA, a calcium chelator, potentiated the...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1985.tb02611.x
更新日期:1985-01-01 00:00:00
abstract:AIM:To assess the effect of Schisandra sphenanthera extract (SchE) on the pharmacokinetics of tacrolimus in healthy volunteers. METHODS:Twelve healthy male volunteers were orally treated with SchE, three capsules twice daily for 13 days. Pharmacokinetic investigations of oral tacrolimus administration at 2 mg were per...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.2007.02922.x
更新日期:2007-10-01 00:00:00
abstract::Obesity is a major cause of morbidity and mortality through cardio- and cerebrovascular diseases and cancer. The metabolic consequences of obesity include dyslipidaemia, hypertension, proinflammatory atherogenesis, pre-diabetes and Type 2 diabetes. For a significant proportion of patients, pharmacotherapy to tackle ob...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.2009.03549.x
更新日期:2009-12-01 00:00:00
abstract::1. The elimination of antipyrine was investigated before and after intravenous administration of haem arginate (3 mg haem kg-1 day-1 on three or four successive days) to six patients with variegate porphyria in remission. 2. Haem arginate decreased the faecal content of protoporphyrin from 557 +/- 91 to 118 +/- 32 (me...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1988.tb05315.x
更新日期:1988-12-01 00:00:00
abstract:AIMS:5-HT1B-receptor mediated vasoconstriction of cranial arteries is a potential mechanism by which 5-HT1B/1D-receptor agonists such as sumatriptan produce their antimigraine effects. 5-HT1B-receptors exist in other blood vessels which may give rise to unwanted vascular effects. Therefore we examined the distribution ...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1046/j.0306-5251.2001.01536.x
更新日期:2002-03-01 00:00:00
abstract::The kinetics of a single 0.5 mg oral dose of the triazolobenzodiazepine hypnotic triazolam, were studied in 54 healthy young men aged 20-44 years, with a mean body weight of 77 kg. Triazolam kinetics were determined from multiple plasma concentrations measured during 14 h post-dose. The overall mean +/- s.e. mean (wit...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1986.tb02951.x
更新日期:1986-12-01 00:00:00
abstract::1. The pharmacokinetics and tolerability of a new nonsteroidal anti-inflammatory drug (NSAID), meloxicam, administered i.m., were investigated in two studies conducted in healthy male volunteers. Study 1 was an open, placebo-controlled design in which 32 volunteers were randomized to a single ascending i.m. dose of me...
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.1365-2125.1996.tb00171.x
更新日期:1996-02-01 00:00:00
abstract:AIMS:This paper describes the pharmacokinetics and effects of propofol in short-term sedated paediatric patients. METHODS:Six mechanically ventilated children aged 1-5 years received a 6 h continuous infusion of propofol 6% at the rate of 2 or 3 mg kg-1 h-1 for sedation following cardiac surgery. A total of seven arte...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1046/j.1365-2125.2002.01652.x
更新日期:2002-10-01 00:00:00
abstract:AIMS:Grapefruit juice inhibits CYP3A4 in the intestinal wall leading to a reduced intestinal first pass metabolism and thereby an increased oral bioavailability of certain drugs. For example, it has been shown that the oral bioavailability of midazolam, a CYP3A4 substrate, increased by 52% in healthy subjects after ing...
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.1365-2125.2002.01615.x
更新日期:2002-08-01 00:00:00
abstract::1 The effect of an intravenous bolus of labetalol (0.6--1.6 mg/kg body weight) on central and peripheral haemodynamics was studied in nine subjects with essential hypertension and in eleven subjects with chronic renal disease and hypertension. 2 The BP reduction amounting to 20/13 mmHg was entirely due to the lowering...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:
更新日期:1979-01-01 00:00:00
abstract:AIMS:To study the potential drug interaction between cimetidine and caffeine in a group of children who received cimetidine for gastritis. METHODS:The caffeine breath test was carried out prior to the administration of cimetidine and after 2-3 weeks therapy. The children (n = 1) received 300-800 mg cimetidine daily (1...
journal_title:British journal of clinical pharmacology
pub_type: 临床试验,杂志文章
doi:10.1046/j.1365-2125.1997.00589.x
更新日期:1997-05-01 00:00:00
abstract:AIM:To assess the relative contribution of intestinal and hepatic CYP3A inhibition to the interaction between the prototypic CYP3A substrate midazolam and clarithromycin in the elderly. METHODS:On day 1, 16 volunteers (eight male, eight female) aged 65-75 years weighing 59-112 kg received simultaneous doses of midazol...
journal_title:British journal of clinical pharmacology
pub_type: 临床试验,杂志文章
doi:10.1111/j.1365-2125.2007.02970.x
更新日期:2008-01-01 00:00:00
abstract:AIMS:Potassium channel openers (KCOs) are of potential therapeutic value. Little is known about the effect of these drugs on human conduit arteries used as coronary bypass grafts. The purpose of this study was to determine the effect of the KCO aprikalim (RP52891) on human arteries used as coronary bypass grafts with e...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1046/j.1365-2125.1997.00640.x
更新日期:1997-10-01 00:00:00
abstract:AIMS:The effect of age on duloxetine pharmacokinetics was evaluated in healthy volunteers and in patients with urinary incontinence. METHODS:Twenty-four healthy subjects (12 women 65-77 years, and 12 women 32-50 years) were given a single 40-mg oral dose of duloxetine in Study 1. Plasma concentration-time data were an...
journal_title:British journal of clinical pharmacology
pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
doi:10.1046/j.1365-2125.2003.01963.x
更新日期:2004-01-01 00:00:00
abstract::Plasma melatonin was used to determine overall beta-adrenergic transmission through pineal neuro-effector junctions during desmethylimipramine (DMI) treatment in 10 normal subjects. Changes in plasma melatonin indicated that an initial increase in noradrenaline (NA) transmission produced by DMI was counteracted by ada...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1985.tb02717.x
更新日期:1985-06-01 00:00:00
abstract::WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT Reflux oesophagitis is a common clinical disorder associated with significant morbidity. Proton pump inhibitors are the current pharmacotherapy of choice, but not all treated patients achieve symptom relief. Little is known about the efficacy of mosapride, a prokinetic agent wh...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章,随机对照试验
doi:10.1111/j.1365-2125.2010.03696.x
更新日期:2010-08-01 00:00:00
abstract::1. The effect of nomifensine on the uptake of 5-hydroxytryptamine (5-HT) and dopamine (DA) into human platelet-rich plasma has been studied. 2. A significant inhibition of DA uptake was observed at nomifensine 10(-6) M. 3. 5-HT uptake was significantly inhibited only at nomifensine 10(-4) M or more. 4. These results a...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1977.tb05745.x
更新日期:1977-01-01 00:00:00
abstract::1 The effect of an intravenous bolus of labetalol (0.6-1.6 mg/kg body weight) on central and peripheral haemodynamics was studied in nine subjects with essential hypertension and in eleven subjects with chronic renal disease and hypertension. 2 The BP reduction amounting to 20/13 mmHg was entirely due to the lowering ...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1979.tb04764.x
更新日期:1979-04-01 00:00:00
abstract::1. The pharmacokinetics of levodopa and paracetamol after single oral doses have been investigated in eight healthy young volunteers in the fasted state and following isocaloric meals containing either 10.5 g or 30.5 g of protein. 2. The initial peak and maximum plasma drug concentrations and the times at which these ...
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.1365-2125.1991.tb05555.x
更新日期:1991-04-01 00:00:00
abstract:AIMS:Surgical site infections contribute to morbidity and mortality after surgery. The authors hypothesized that higher antibiotic tissue concentrations can be reached for a prolonged time span by continuous administration of prophylactic cefuroxime compared to bolus administration. METHODS:Twelve patients undergoing ...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/bcp.13865
更新日期:2019-04-01 00:00:00
abstract::1. The in vitro metabolism of omeprazole was studied in human liver microsomes in order to define the secondary metabolic pathways and identify the cytochrome P450 (CYP) isoforms responsible for the formation of the secondary metabolites of omeprazole. 2. The major secondary omeprazole metabolite was the hydroxysulpho...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1994.tb04310.x
更新日期:1994-06-01 00:00:00
abstract::The frequency distributions of the 0-8 h urinary metabolic ratios of debrisoquine and mephenytoin were measured in 111 healthy, unrelated Sinhalese resident in Sri Lanka. Blood samples were taken from 77 of these subjects for CYP2D6 genotyping. Bimodality in the distribution of the log10 debrisoquine/4-hydroxydebrisoq...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1994.tb04384.x
更新日期:1994-11-01 00:00:00
abstract:AIMS:To explore longitudinal changes in the number and type of medicines used among older people who experience polypharmacy. METHODS:We used pharmaceutical claims for a 10% sample of Australian Pharmaceutical Benefits Scheme beneficiaries to identify people aged 70 years and older who were exposed to 5 or more medici...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/bcp.14504
更新日期:2020-07-31 00:00:00
abstract::The kinetics of flecainide after single intravenous (2 mg kg-1) and oral (200 mg) dosing, absolute bioavailability, effects of food and aluminium hydroxide on flecainide absorption and steady-state kinetics following twice daily oral dosing (200 mg) have been evaluated in ten healthy subjects. Absolute bioavailability...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1986.tb02892.x
更新日期:1986-09-01 00:00:00
abstract::1 Cumulative dose-response curves (FEV1) to pressurized aerosol salbutamol were established in 17 patients admitted to hospital with acute severe asthma. After the maximal pressurized aerosol effect had been achieved, a further dose (5 mg) of salbutamol was given by wet nebulizer and any further increment recorded. 2 ...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1980.tb01776.x
更新日期:1980-10-01 00:00:00
abstract:AIM:Lamivudine is used as first line therapy in HIV-infected children. Yet, like many other paediatric drugs, its dose rationale has been based on limited clinical data, without thorough understanding of the effects of growth on drug disposition. Here we use lamivudine to show how a comprehensive population pharmacokin...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/bcp.12247
更新日期:2014-05-01 00:00:00