Abstract：
OBJECTIVE:To determine the effects of itraconazole, a potent inhibitor of CYP3A4, on the pharmacokinetics of cerivastatin, a competitive 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor. METHODS:A randomized, double-blind, cross-over study design with two phases, which were separated by a washout period of 4 weeks, was used. In each phase ten healthy volunteers took 200 mg itraconazole or matched placebo orally once daily for 4 days according to a randomization schedule. On day 4, 0.3 mg cerivastatin was administered orally. Serum concentrations of cerivastatin, its major metabolites, active and total HMG-CoA reductase inhibitors, itraconazole and hydroxyitraconazole were measured up to 24 h. RESULTS:Itraconazole increased the area under the concentration-time curve from time zero to infinity (AUC(0-infinity)) of the parent cerivastatin by 15% (P < 0.05). The mean peak serum concentration (Cmax) of cerivastatin lactone was increased 1.8-fold (range 1.1-fold to 2.4-fold, P < 0.001) and the AUC(0-24h) 2.6-fold (range 2.0-fold to 3.6-fold, P < 0.001) by itraconazole. The elimination half-life (t1/2) of cerivastatin lactone was increased 3.2-fold (P < 0.001). Itraconazole decreased the AUC(0-24h) of the active M-1 metabolite of cerivastatin by 28% (P < 0.05), whereas the AUC(0- 24h) of the more active metabolite, M-23, was increased by 36% (P < 0.05). The AUC(0-24h) and t1/2 of active HMG-CoA reductase inhibitors were increased by 27% (P < 0.05) and 40% (P < 0.05), respectively, by itraconazole. CONCLUSIONS:Itraconazole has a modest interaction with cerivastatin. Inhibition of the CYP3A4-mediated M-1 metabolic pathway leads to elevated serum concentrations of cerivastatin, cerivastatin lactone and metabolite M-23, resulting in increased concentrations of active HMG-CoA reductase inhibitors.
journal_name
Eur J Clin Pharmacoljournal_title
European journal of clinical pharmacologyauthors
Kantola T,Kivistö KT,Neuvonen PJdoi
10.1007/s002280050566subject
Has Abstractpub_date
1999-01-01 00:00:00pages
851-5issue
11eissn
0031-6970issn
1432-1041journal_volume
54pub_type
临床试验,杂志文章,随机对照试验abstract：OBJECTIVE:To investigate the drug interaction potential between itraconazole and nevirapine. METHODS:Our study was conducted in 12 healthy volunteers in two phases. In phase 1 (from days 1-28), all subjects were randomly assigned to a two-way crossover study of a nevirapine regimen (nevirapine 200 mg once daily for 7 ...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章,随机对照试验
doi：10.1007/s00228-007-0280-x
更新日期：2007-05-01 00:00:00
abstract：:Sixty patients were treated for 1 year for essential uncomplicated hypertension, 30 with beta-blockers alone (BB) and 30 with BB and chlorthalidone (CTD). BB did not affect serum K+ or Mg++. In the BB-group there was a statistically significant trend towards retention of Mg++ in a loading test, but the effect was clin...
journal_title：European journal of clinical pharmacology
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1007/BF00543964
更新日期：1987-01-01 00:00:00
abstract：:The effects in vitro and in vivo of triiodothyronine on certain functions of human lymphocytes and polymorphonuclear granulocytes have been investigated. Triiodothyronine was able to enhance the phagocytic capacity and chemiluminescent activity of polymorphonuclear granulocytes. PHA-P-induced 3H-thymidine incorporatio...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00561672
更新日期：1980-01-01 00:00:00
abstract：:The pharmacokinetics of a new sustained-release preparation of theophylline (Dilatrane à Action Prolongée capsules filled with homogenous microgranules) has been after its studied administration to 7 healthy volunteers at 8 p.m. in order to achieve therapeutic levels at night and in the morning. In separate trials the...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00542169
更新日期：1984-01-01 00:00:00
abstract：OBJECTIVE:To evaluate the impact of the two most common CYP2C9 variant alleles (*2 and *3) on the maintenance dose of warfarin and on the quality of anticoagulation control in Brazilians. METHODS:Patients (n = 103) initiated warfarin therapy with 5 mg/day (or 2.5 mg/day when over 80 years old). The international norma...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s00228-007-0385-2
更新日期：2008-01-01 00:00:00
abstract：PURPOSE:Tamsulosin is one of the most potent drugs currently available to treat benign prostatic hyperplasia. Cytochrome P450 (CYP) 2D6 and CYP3A are the two major enzymes responsible for tamsulosin metabolism. The purpose of this study was to evaluate the effects of CYP2D6 and CYP3A5 genetic polymorphisms on the pharm...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s00228-018-2501-x
更新日期：2018-10-01 00:00:00
abstract：PURPOSE:A population pharmacokinetic analysis was performed to define domperidone pharmacokinetic parameters in preterm neonates, as no pharmacokinetic data are available in this population. METHODS:An oral domperidone solution was administered (0.75 mg/kg per day) in 32 preterm neonates (64 samples). Domperidone plas...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s00228-008-0535-1
更新日期：2008-12-01 00:00:00
abstract：:The linearity of the pharmacokinetics of the metamizol metabolites 4-methyl-amino-antipyrine (4-MAA), 4-amino-antipyrine (4-AA), 4-formyl-aminoantipyrine (4-FAA), and 4-acetyl-amino-antipyrine (4-AcAA) has been studied after administration to 15 healthy male volunteers of single oral doses of 750, 1500, and 3000 mg me...
journal_title：European journal of clinical pharmacology
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1007/BF00314805
更新日期：1990-01-01 00:00:00
abstract：PURPOSE:The use of melatonin is increasing among Swedish children and adolescents despite deficient knowledge of usage in these groups. The aim of this study was to investigate the use of melatonin in Swedish children and adolescents according to age, gender, dosage, treatment duration, and use of attention deficit hyp...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s00228-015-1866-3
更新日期：2015-07-01 00:00:00
abstract：:Red cell folate concentrations were determined in 74 epileptic women in early pregnancy in a prospective study. All patients were treated continuously with antiepileptic drugs since before conception. The most frequently used drugs were carbamazepine (n = 39) and phenytoin (n = 26). Sixty-four patients (86%) were on m...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00198317
更新日期：1995-01-01 00:00:00
abstract：:The use of bioelectrical impedance (BI) analysis as a non-invasive approach for individualizing gentamicin therapy in newborn infants has been investigated in a two phase study. In Phase I, 1/impedance and length were identified as statistically significant predictors of the distribution volume of gentamicin (Adj R2 =...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00271367
更新日期：1993-01-01 00:00:00
abstract：:The antihypertensive effect of labetalol (L) was compared with that of clonidine (C) in a randomized cross-over study in 17 hypertensive outpatients on bendrofluazide (B). After treatment for two weeks with B(5 mg qd), either L (100 mg tid) or C (0.1 mg tid) was given and their doses were titrated at 2-weekly visits u...
journal_title：European journal of clinical pharmacology
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1007/BF00542319
更新日期：1982-01-01 00:00:00
abstract：PURPOSE:To develop a limited sampling strategy (LSS) to predict area under the concentration-time curve (AUC) ratios of omeprazole (AUC(OPZ)) to its metabolites 5-hydroxyomeprazole (AUC(5OH)) and omeprazole sulfone (AUC(SUL)) as phenotyping parameters for cytochrome P450 (CYP) 2C19 and 3A. METHODS:Data were obtained f...
journal_title：European journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1007/s00228-011-1136-y
更新日期：2012-04-01 00:00:00
abstract：OBJECTIVE:The prevention of contrast-mediated nephropathy (CMN), which accounts for considerable morbidity and mortality, remains a vexing problem. Contrast induced renal vasoconstriction is believed to play a pivotal role in the CMN mechanism. The aim of this pilot study was to examine the safety and efficacy of two d...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章,随机对照试验
doi：10.1007/s00228-006-0150-y
更新日期：2006-08-01 00:00:00
abstract：OBJECTIVE:To describe trends in opioid consumption in Israel (morphine, methadone, oxycodone, pethidine, fentanyl, buprenorphine, codeine, and dextropropoxyphene) over the 9 years, 2000-2008, and to explore explanations for changes in consumption, in amounts and the pattern. METHODS:Data for the 2000-2008 period (all ...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s00228-010-0932-0
更新日期：2011-02-01 00:00:00
abstract：:The benzamide-derivative moclobemide (Ro 11-1163) is a new short-acting, reversible MAO-inhibitor, preferentially affecting Type A MAO, which is, being developed as an antidepressant agent. The effect of moclobemide on heart rate, blood pressure, electrocardiographic and systolic time intervals was assessed in eight h...
journal_title：European journal of clinical pharmacology
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1007/BF00543787
更新日期：1983-01-01 00:00:00
abstract：PURPOSE:Until recently, ondansetron was approved for the prevention of nausea and vomiting only in patients older than 2 years. However, as the use of ondansetron in patients younger than 2 years had been documented, characterization of ondansetron pharmacokinetics in this younger pediatric age group was warranted. ME...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章,多中心研究
doi：10.1007/s00228-009-0730-8
更新日期：2010-01-01 00:00:00
abstract：PURPOSE:Clomipramine is one of the drugs for depression during pregnancy; however, pharmacokinetic data of clomipramine and its active metabolite desmethylclomipramine in this vulnerable period are lacking. In this study, we describe clomipramine and desmethylclomipramine concentrations including their ratios during pr...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s00228-015-1944-6
更新日期：2015-12-01 00:00:00
abstract：:A four-period, two-panel, single-rising-dose study (0.1-100 mg) was conducted in healthy males to investigate the pharmacodynamics, tolerability and pharmacokinetics of MK-0434, a steroid 5 alpha-reductase inhibitor. MK-0434 was associated with a significant reduction in dihydrotestosterone, which was maximal at 24 h ...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00199874
更新日期：1994-01-01 00:00:00
abstract：OBJECTIVES:Digoxin is a well-known probe for the activity of P-glycoprotein. The objective of this work was to apply different methods for covariate selection in non-linear mixed-effect models to study the relationship between the pharmacokinetic parameters of digoxin and the genotype for two major exons located on the...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s00228-007-0269-5
更新日期：2007-05-01 00:00:00
abstract：:The haemodynamic effects of prenalterol, a new beta-1 agonist, were studied in 10 patients with chronic heart failure. Following intravenous prenalterol infusions of 1 mg, 2.5 mg and 5 mg at 15 min intervals, oral slow release prenalterol 20 mg, 30 mg and 50 mg was given at 2 h intervals and then 50-100 mg bid for one...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00542125
更新日期：1983-01-01 00:00:00
abstract：PURPOSE:To comparatively assess the prevalence rates of potentially inappropriate medications (PIMs) obtained by the former and latest versions of American Geriatrics Society Beers Criteria (AGS BC) and screening tool of older person's potentially inappropriate prescriptions (STOPP), and analyze the factors of influenc...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s00228-019-02722-0
更新日期：2019-10-01 00:00:00
abstract：PURPOSE:Vancomycin (VCM) is used for the treatment of methicillin-resistant Staphylococcus aureus. Although the risk factors for VCM nephrotoxicity have been evaluated, the time course of renal function during VCM treatment is unknown. We assessed risk factors for VCM nephrotoxicity and how renal function varied over t...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s00228-019-02648-7
更新日期：2019-06-01 00:00:00
abstract：:The effect of procainamide (P) on left ventricular function as measured by the systolic time intervals (STI) was studied in 14 patients with primary myocardial disease. P, 7.5 mg/kg body weight, was given intravenously at a rate of 100 mg per minute. Administration of P produced a decrease in left ventricular performa...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00561387
更新日期：1980-10-01 00:00:00
abstract：:Hemodynamic changes for 30 min after intravenous administration of molsidomin 4 mg were studied in 10 patients. Pulmonary artery pressure, pulmonary wedge pressure, right atrial pressure and aortic pressure decreased significantly after 15 min, and after 30 min they were still below the control level. Heart rate incre...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00716357
更新日期：1978-06-19 00:00:00
abstract：:We have compared the effect on ventilation of ketorolac, an injectable non-steroidal analgesic, with that of morphine in a randomized, double-blind, cross-over study, using two doses of ketorolac (10 and 90 mg i.m.) and one of morphine (10 mg i.m.). The effect on ventilation was measured with a CO2 rebreathing techniq...
journal_title：European journal of clinical pharmacology
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1007/BF00558243
更新日期：1988-01-01 00:00:00
abstract：:The pharmacokinetics of biperiden was studied and compared with pharmacodynamics (pupil size, accommodation, self-rating mood scale) in 6 healthy volunteers. A single-blind cross-over design was employed with placebo and biperiden (4 mg as commercially available tablets). After a lag time of 0.5 h, biperiden was rapid...
journal_title：European journal of clinical pharmacology
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1007/BF00556903
更新日期：1984-01-01 00:00:00
abstract：INTRODUCTION:Body position may influence physiological characteristics, such as perfusion, gastrointestinal function and plasma volume. These characteristics may interact with key factors determining the pharmacokinetics of drugs (dissolution, absorption, distribution, metabolism, excretion). OBJECTIVES:Based on a sys...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章,评审
doi：10.1007/s00228-008-0579-2
更新日期：2009-02-01 00:00:00
abstract：OBJECTIVE:To determine the incidence of errors in preparing and administering intravenous (i.v.) drugs, identify the stages in the process at which errors occurred and evaluate their clinical importance. METHODS:A prospective ethnographic study using disguised observation was carried out on two wards in one German non...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s00228-003-0689-9
更新日期：2004-01-01 00:00:00
abstract：PURPOSE:To investigate associations between antidepressant use patterns and risk of fatal and non-fatal suicidal behaviours in older adults who initiated antidepressant therapy. METHOD:A national population-based cohort study conducted among Swedish residents aged ≥ 75 years who initiated antidepressant treatment. Pat...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s00228-017-2360-x
更新日期：2018-02-01 00:00:00
