CYP3A5*3 and bilirubin predict midazolam population pharmacokinetics in Asian cancer patients.

Abstract:

:We aim to evaluate the influence of covariates, including cytochrome P450 3A (CYP3A) genetic polymorphisms, on the pharmacokinetics of midazolam (MDZ) in Asian cancer patients, using a population pharmacokinetic approach. Pharmacokinetic data were obtained from 24 adult cancer patients who received an intravenous bolus dose of 1 mg MDZ as a CYP3A phenotyping probe, 1-day before starting FOLFIRI chemotherapy. Concentrations of MDZ and its major metabolites, 1'-hydroxymidazolam (1OHM) and 1'-hydroxymidazolam glucuronide (HMG) were measured using liquid chromatography/mass spectrometry. The population pharmacokinetic study was conducted using NONMEM. Demographics, clinical characteristics, and genetic polymorphisms were screened as covariates. A two-compartment model for MDZ and two sequential compartments representing 1OHM and HMG best described the data. The CYP3A5*3 and total bilirubin level significantly influenced MDZ clearance. The population typical MDZ clearance for CYP3A5*3 expressers was 22% lower than non-expressers. Baseline bodyweight was a statistically significant covariate for clearance and distribution volume of 1OHM. Creatinine clearance was positively correlated with HMG clearance. Our data indicate that CYP3A5*3, total bilirubin, bodyweight, and creatinine clearance are important predictors of MDZ and metabolite pharmacokinetics. Further studies in more patients are needed to explore the links between the identified covariates and the disposition of MDZ and its metabolites.

journal_name

J Clin Pharmacol

authors

Seng KY,Hee KH,Soon GH,Sapari NS,Soong R,Goh BC,Lee LS

doi

10.1002/jcph.230

subject

Has Abstract

pub_date

2014-02-01 00:00:00

pages

215-24

issue

2

eissn

0091-2700

issn

1552-4604

journal_volume

54

pub_type

临床试验,杂志文章
  • Population Pharmacokinetics of Adjunctive Lacosamide in Pediatric Patients With Epilepsy.

    abstract::A pediatric population pharmacokinetic model including covariate effects was developed using data from 2 clinical trials in pediatric patients with epilepsy (SP0847 and SP1047). Lacosamide plasma concentration-time data (n = 402) were available from 79 children with body weights ranging from 6 to 76 kg, and a balanced...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章

    doi:10.1002/jcph.1340

    authors: Winkler J,Schoemaker R,Stockis A

    更新日期:2019-04-01 00:00:00

  • Pharmacokinetics and bioavailability of dilevalol in normotensive volunteers.

    abstract::The bioavailability and pharmacokinetics of dilevalol following oral and intravenous administration were investigated in 12 healthy male volunteers. Dilevalol HCl was administered as a 200-mg oral tablet and a 50-mg intravenous infusion using a randomized cross-over design. Blood and urine samples were collected over ...

    journal_title:Journal of clinical pharmacology

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:10.1002/j.1552-4604.1988.tb03189.x

    authors: Kramer WG,Nagabhushan N,Affrime MB,Perentesis GP,Symchowicz S,Patrick JE

    更新日期:1988-07-01 00:00:00

  • Reproducibility of dorsal hand vein responses to phenylephrine and prostaglandin F2 alpha using the dorsal hand vein compliance method.

    abstract::Assessment of drug-induced venodilation by the dorsal hand vein compliance method requires stable constriction of the vein. This study was designed to investigate intra- and intersubject reproducibility of the venous preconstriction technique in response to phenylephrine and prostaglandin F2 alpha and to determine the...

    journal_title:Journal of clinical pharmacology

    pub_type: 临床试验,杂志文章

    doi:10.1177/0091270002251004

    authors: Schindler C,Grossmann M,Dobrev D,Francke K,Ravens U,Kirch W

    更新日期:2003-03-01 00:00:00

  • The treatment of acute gout with naproxen.

    abstract::The effectiveness of naproxen in the management of acute gouty arthritis was assessed in an open study of 20 patients. These patients were selected on the basis of their clinical presentation of characteristic acute arthritis associated in 19 with concomitant hyperuricemia. There were 17 men and three women varying in...

    journal_title:Journal of clinical pharmacology

    pub_type: 临床试验,杂志文章

    doi:10.1002/j.1552-4604.1975.tb01465.x

    authors: Willkens RF,Case JB,Huix FJ

    更新日期:1975-04-01 00:00:00

  • Target-Mediated Drug Disposition-A Class Effect of Soluble Epoxide Hydrolase Inhibitors.

    abstract::Pharmacological target-mediated drug disposition (TMDD) represents a special source of nonlinear pharmacokinetics, and its occurrence in large-molecule compounds has been well recognized because numerous protein drugs have been reported to have TMDD due to specific binding to their pharmacological targets. Although TM...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章

    doi:10.1002/jcph.1763

    authors: An G,Lee KSS,Yang J,Hammock BD

    更新日期:2020-10-19 00:00:00

  • Dosing Recommendations for Pediatric Patients With Renal Impairment.

    abstract::A treatment gap exists for pediatric patients with renal impairment. Alterations in renal clearance and metabolism of drugs render standard dosage regimens inappropriate and may lead to drug toxicity, but these studies are not routinely conducted during drug development. The objective of this study was to examine the ...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章

    doi:10.1002/jcph.1676

    authors: Al-Khouja A,Park K,Anderson DJC,Young C,Wang J,Huang SM,Khurana M,Burckart GJ

    更新日期:2020-12-01 00:00:00

  • Meptazinol and morphine in postoperative pain assessed with a new method for onset and duration.

    abstract::Meptazinol, m-(3-ethyl-1-methyl-hexahydro-1-H-azepin-3-yl) phenol hydrochloride is a centrally active opioid analgesic with a specificity for the mu-1 receptor. It has been reported to lack many of the side effects commonly observed with morphine and morphinelike drugs in man. The objective of this study was to assess...

    journal_title:Journal of clinical pharmacology

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:10.1002/j.1552-4604.1989.tb03272.x

    authors: Siegel C,Sunshine A,Richman H,Olson NZ,Robissa N,Cordone R,Estrada N,Laska E

    更新日期:1989-11-01 00:00:00

  • Interaction trial between artemether-lumefantrine (Riamet) and quinine in healthy subjects.

    abstract::Forty-two healthy Caucasian subjects were randomized in a double-blind, parallel three-group study (14 subjects per group) to investigate potential electrocardiographic and pharmacokinetic interactions between the antimalarials artemether-lumefantrine (six-dose regimen of Riamet over 3 days) and quinine (2-h intraveno...

    journal_title:Journal of clinical pharmacology

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:10.1177/009127002401382632

    authors: Lefèvre G,Carpenter P,Souppart C,Schmidli H,Martin JM,Lane A,Ward C,Amakye D

    更新日期:2002-10-01 00:00:00

  • Evaluation of the Relationship of Glasdegib Exposure and Safety End Points in Patients With Refractory Solid Tumors and Hematologic Malignancies.

    abstract::Glasdegib is approved for treating acute myeloid leukemia in elderly patients at 100 mg once daily in combination with low-dose cytarabine. Exposure-efficacy analysis showed that the survival benefit of glasdegib was not glasdegib exposure-dependent. The relationship between glasdegib exposure and adverse event (AE) c...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章

    doi:10.1002/jcph.1742

    authors: Ruiz-Garcia A,Shaik N,Lin S,Jamieson C,Heuser M,Chan G

    更新日期:2021-03-01 00:00:00

  • Epoprostenol (PGI2, prostacyclin) during high-risk hemodialysis: preventing further bleeding complications.

    abstract::The frequency of hemodialysis-associated hemorrhage was studied prospectively in two successive, parallel, heparin-controlled studies using epoprostenol (PGI2; average dose, 4.1 ng/kg.min) as the sole antithrombotic agent. Sixty-three patients with active or recently active bleeding underwent 163 hemodialysis treatmen...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章

    doi:10.1002/j.1552-4604.1988.tb03222.x

    authors: Swartz RD,Flamenbaum W,Dubrow A,Hall JC,Crow JW,Cato A

    更新日期:1988-09-01 00:00:00

  • Pharmacokinetics of gabapentin in a novel gastric-retentive extended-release formulation: comparison with an immediate-release formulation and effect of dose escalation and food.

    abstract::The objectives of the 3 phase I studies described herein were (1) to compare the pharmacokinetics of gabapentin delivered from a novel gastric-retentive dosage form vs an immediate-release formulation, (2) to assess the dose proportionality of the gastric-retentive extended-release formulation, and (3) to determine th...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章,随机对照试验

    doi:10.1177/0091270010368411

    authors: Chen C,Cowles VE,Hou E

    更新日期:2011-03-01 00:00:00

  • First-in-Human Study to Assess the Safety, Pharmacokinetics, and Pharmacodynamics of an Oral Formulation of DS-1040, an Inhibitor of the Activated Form of Thrombin-Activatable Fibrinolysis Inhibitor, in Healthy Subjects.

    abstract::DS-1040, a low-molecular-weight imidazole derivative, inhibits the enzymatic activity of thrombin-activatable fibrinolysis inhibitor (TAFIa), enhancing endogenous tissue plasminogen activator-triggered fibrinolysis. This first-in-human, randomized, placebo-controlled, phase 1 study evaluated the safety, pharmacokineti...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章,随机对照试验

    doi:10.1002/jcph.1474

    authors: Zhou J,Limsakun T,Yin O,Warren V,Zamora C,Atiee G,Kochan J,Pav J,Kobayashi F,Vashi V,Dishy V

    更新日期:2019-12-01 00:00:00

  • Are patients reliable when self-reporting medication use? Validation of structured drug interviews and home visits by drug analysis and prescription data in acutely hospitalized patients.

    abstract::The medication history among hospitalized patients often relies on patients' self-reports due to insufficient communication between health care professionals. The aim of the present study was to estimate the reliability of patients' self-reported medication use. Five hundred patients admitted to an acute medical depar...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章

    doi:10.1177/0091270007307243

    authors: Glintborg B,Hillestrøm PR,Olsen LH,Dalhoff KP,Poulsen HE

    更新日期:2007-11-01 00:00:00

  • Safety, tolerability, pharmacokinetics, and pharmacodynamic properties of taranabant, a novel selective cannabinoid-1 receptor inverse agonist, for the treatment of obesity: results from a double-blind, placebo-controlled, single oral dose study in health

    abstract::Taranabant is a novel cannabinoid CB-1 receptor (CB1R) inverse agonist in clinical development for the treatment of obesity. This double-blind, randomized, placebo-controlled, single oral dose study evaluated the safety, tolerability, pharmacokinetics, and pharmacodynamics of taranabant (0.5-600 mg) in 24 healthy male...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章,随机对照试验

    doi:10.1177/0091270008314467

    authors: Addy C,Li S,Agrawal N,Stone J,Majumdar A,Zhong L,Li H,Yuan J,Maes A,Rothenberg P,Cote J,Rosko K,Cummings C,Warrington S,Boyce M,Gottesdiener K,Stoch A,Wagner J

    更新日期:2008-04-01 00:00:00

  • Acute effects of the new angiotensin-converting enzyme inhibitor cilazapril: a pilot study.

    abstract::This study assesses the magnitude and duration of action of three different oral doses of the new orally active angiotensin-converting enzyme (ACE) inhibitor RO 312848 (cilazapril, Hoffman-LaRoche, Nutley, NJ) on blood pressure and plasma ACE levels. Twelve hypertensive patients were separated into two groups: Group A...

    journal_title:Journal of clinical pharmacology

    pub_type: 临床试验,杂志文章

    doi:10.1002/j.1552-4604.1988.tb03194.x

    authors: Mulinari RA,Gouni I,Gavras I,Gavras H

    更新日期:1988-07-01 00:00:00

  • Multiple-dose pharmacokinetics, pharmacodynamics, and safety of taranabant, a novel selective cannabinoid-1 receptor inverse agonist, in healthy male volunteers.

    abstract::Taranabant is a cannabinoid-1 receptor inverse agonist for the treatment of obesity. This study evaluated the safety, pharmacokinetics, and pharmacodynamics of taranabant (5, 7.5, 10, or 25 mg once daily for 14 days) in 60 healthy male subjects. Taranabant was rapidly absorbed, with a median t(max) of 1.0 to 2.0 hours...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章,随机对照试验

    doi:10.1177/0091270008317591

    authors: Addy C,Rothenberg P,Li S,Majumdar A,Agrawal N,Li H,Zhong L,Yuan J,Maes A,Dunbar S,Cote J,Rosko K,Van Dyck K,De Lepeleire I,de Hoon J,Van Hecken A,Depré M,Knops A,Gottesdiener K,Stoch A,Wagner J

    更新日期:2008-06-01 00:00:00

  • A model for estimating individualized valproate clearance values in children.

    abstract::To evaluate the population pharmacokinetics of valproic acid in children, 97 steady-state serum valproate concentration measurements were gathered during normal, routine, outpatient care of 52 children with epilepsy (1.2-16 years of age). Levels were obtained from patients receiving valproate monotherapy (49%) or valp...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章

    doi:10.1002/j.1552-4604.1995.tb04020.x

    authors: Botha JH,Gray AL,Miller R

    更新日期:1995-10-01 00:00:00

  • Therapeutic advances in migraine.

    abstract::Migraine is a common and debilitating disorder of uncertain pathogenesis. Recent research into the pathophysiology of migraine and serotonin receptors has revolutionized the approach to pharmacotherapy. New medications, such as sumatriptan, and new dosage forms of older medications, including dihydroergotamine, NSAIDs...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章,评审

    doi:10.1002/j.1552-4604.1993.tb03944.x

    authors: Solomon GD

    更新日期:1993-03-01 00:00:00

  • A novel CRTH2 antagonist: Single- and multiple-dose tolerability, pharmacokinetics, and pharmacodynamics of ACT-453859 in healthy subjects.

    abstract::The chemoattractant receptor-homologous molecule expressed on T-helper 2 cells (CRTH2) is a G-protein-coupled receptor for prostaglandin D2 , a key mediator in inflammatory disorders. In this randomized, double-blind, placebo-controlled study we investigated the single- and multiple-dose tolerability, pharmacokinetics...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章,随机对照试验

    doi:10.1002/jcph.478

    authors: Géhin M,Strasser DS,Zisowsky J,Farine H,Groenen PM,Dingemanse J,Sidharta PN

    更新日期:2015-07-01 00:00:00

  • Enhanced sensitivity to drug-induced QT interval lengthening in patients with heart failure due to left ventricular systolic dysfunction.

    abstract::Patients with heart failure (HF) are at increased risk for drug-induced torsades de pointes (TdP) due to unknown mechanisms. Our objective was to determine if sensitivity to drug-induced QT interval lengthening is enhanced in patients with HF. In this multicenter, prospective study, 15 patients with atrial fibrillatio...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章

    doi:10.1177/0091270011416939

    authors: Tisdale JE,Overholser BR,Wroblewski HA,Sowinski KM,Amankwa K,Borzak S,Kingery JR,Coram R,Zipes DP,Flockhart DA,Kovacs RJ

    更新日期:2012-09-01 00:00:00

  • Combination drug therapy with calcium-channel blockers in the treatment of systemic hypertension.

    abstract::Calcium-channel blockers have been shown to be both safe and effective for treatment of patients with systemic hypertension. These drugs reduce peripheral vascular resistance predominantly by the inhibition of transmembrane calcium ion fluxes in vascular smooth muscle, and by this mechanism can reduce elevated blood p...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章,评审

    doi:10.1002/j.1552-4604.1993.tb05619.x

    authors: Frishman WH,Landau A,Cretkovic A

    更新日期:1993-08-01 00:00:00

  • Optimal Designs for Model-Based Assessment of Insulin Sensitivity and Glucose Effectiveness.

    abstract::The integrated minimal model allows assessment of clinical diagnosis indices, for example, insulin sensitivity (SI ) and glucose effectiveness (SG ), from data of the insulin-modified intravenous glucose tolerance test (IVGTT), which is laborious with an intense sampling schedule, up to 32 samples. The aim of this stu...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章

    doi:10.1002/jcph.1707

    authors: Ibrahim MMA,Redestad E,Kjellsson MC

    更新日期:2021-01-01 00:00:00

  • Third generation cephalosporins: safety profiles after 10 years of clinical use.

    abstract::Compared with aminoglycosides, chloramphenicol, sulfonamides, tetracyclines, and even penicillins, the cephalosporins represent a remarkably safe class of antibiotics. Among the cephalosporins, the extended spectrum, third generation agents developed generally produce few side effects and appear to be less allergenic ...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章,评审

    doi:10.1002/j.1552-4604.1990.tb03476.x

    authors: Neu HC

    更新日期:1990-05-01 00:00:00

  • Differences in drug pharmacokinetics between East Asians and Caucasians and the role of genetic polymorphisms.

    abstract::Interethnic variability in pharmacokinetics can cause unexpected outcomes such as therapeutic failure, adverse effects, and toxicity in subjects of different ethnic origin undergoing medical treatment. It is important to realize that both genetic and environmental factors can lead to these differences among ethnic gro...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章,评审

    doi:10.1177/0091270004268128

    authors: Kim K,Johnson JA,Derendorf H

    更新日期:2004-10-01 00:00:00

  • The uricosuric effect of oxaprozin in humans.

    abstract::The effects of oxaprozin, a new investigational propionic acid analogue, and indomethacin on uric acid metabolism were compared in 12 healthy volunteers receiving either agent, first as a single dose and then daily for seven days. While indomethacin did not alter either serum or urinary uric acid values, oxaprozin cau...

    journal_title:Journal of clinical pharmacology

    pub_type: 临床试验,杂志文章

    doi:10.1002/j.1552-4604.1985.tb02815.x

    authors: Goldfarb S,Walker BR,Agus ZS

    更新日期:1985-03-01 00:00:00

  • Long-term efficacy and toxicity of high- and low-dose amiodarone regimens.

    abstract::Amiodarone is an effective antiarrhythmic drug for the control of potentially lethal and lethal ventricular arrhythmias (VA). In the United States, a high-dose regimen has been used at the expense of a high toxicity profile for the control of lethal VAs. Significant antiarrhythmic efficacy has also been established wi...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章,评审

    doi:10.1002/j.1552-4604.1989.tb03354.x

    authors: Kerin NZ,Aragon E,Faitel K,Frumin H,Rubenfire M

    更新日期:1989-05-01 00:00:00

  • The effect of flecainide acetate, a new antiarrhythmic, on plasma digoxin levels.

    abstract::The possible effect of oral flecainide acetate on steady-state digoxin levels was assessed in 15 healthy men. Each volunteer received digoxin 0.25 mg daily (8 AM) for 22 consecutive days and flecainide 200 mg bid (8 AM and 8 PM) on days 11 through 15. Plasma digoxin and flecainide levels were measured by radioimmunoas...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章

    doi:10.1002/j.1552-4604.1986.tb02898.x

    authors: Weeks CE,Conard GJ,Kvam DC,Fox JM,Chang SF,Paone RP,Lewis GP

    更新日期:1986-01-01 00:00:00

  • Pharmacokinetics of anthocyanins and ellagic acid in healthy volunteers fed freeze-dried black raspberries daily for 7 days.

    abstract::Eleven subjects completed a clinical trial to determine the safety/tolerability of freeze-dried black raspberries (BRB) and to measure, in plasma and urine, specific anthocyanins-cyanidin-3-glucoside, cyanidin-3-sambubioside, cyanidin-3-rutinoside, and cyanidin-3-xylosylrutinoside, as well as ellagic acid. Subjects we...

    journal_title:Journal of clinical pharmacology

    pub_type: 临床试验,杂志文章

    doi:10.1177/0091270005279636

    authors: Stoner GD,Sardo C,Apseloff G,Mullet D,Wargo W,Pound V,Singh A,Sanders J,Aziz R,Casto B,Sun X

    更新日期:2005-10-01 00:00:00

  • Characterization of Neutropenia in Advanced Cancer Patients Following Palbociclib Treatment Using a Population Pharmacokinetic-Pharmacodynamic Modeling and Simulation Approach.

    abstract::Neutropenia is the most commonly reported hematologic toxicity following treatment with palbociclib, a cyclin-dependent kinase 4/6 inhibitor approved for metastatic breast cancer. Using data from 185 advanced cancer patients receiving palbociclib in 3 clinical trials, a pharmacokinetic-pharmacodynamic model was develo...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章,随机对照试验

    doi:10.1002/jcph.902

    authors: Sun W,O'Dwyer PJ,Finn RS,Ruiz-Garcia A,Shapiro GI,Schwartz GK,DeMichele A,Wang D

    更新日期:2017-09-01 00:00:00

  • Pharmacokinetics and rectal bioavailability of hydrocortisone acetate after single and multiple administration in healthy subjects and patients.

    abstract::The pharmacokinetics and bioavailability of hydrocortisone after rectal administration of a hydrocortisone acetate foam were determined after single and multiple dosing in healthy subjects as well as in patients with inflammatory bowel disease. Endogenous hydrocortisone was suppressed by dexamethasone administration. ...

    journal_title:Journal of clinical pharmacology

    pub_type: 临床试验,杂志文章

    doi:10.1177/00912700122010410

    authors: Tromm A,Möllmann H,Barth J,Hochhaus G,Krieg M,Bigalke C,Möllmann A,Derendorf H

    更新日期:2001-05-01 00:00:00