Population pharmacokinetics of empagliflozin, a sodium glucose cotransporter 2 inhibitor, in patients with type 2 diabetes.

Abstract:

:Data from five randomized, placebo-controlled, multiple oral dose studies of empagliflozin in patients with type 2 diabetes mellitus (T2DM; N = 974; 1-100 mg q.d.; ≤12 weeks) were used to develop a population pharmacokinetic (PK) model for empagliflozin. The model consisted of two-compartmental disposition, lagged first-order absorption and first-order elimination, and incorporated appropriate covariates. Population estimates (interindividual variance, CV%) of oral apparent clearance, central and peripheral volumes of distribution, and inter-compartmental clearance were 9.87 L/h (26.9%), 3.02 L, 60.4 L (30.8%), and 5.16 L/h, respectively. An imposed allometric weight effect was the most influential PK covariate effect, with a maximum effect on exposure of ±30%, using 2.5th and 97.5th percentiles of observed weights, relative to the median observed weight. Sex and race did not lend additional description to PK variability beyond allometric weight effects, other than ∼25% greater oral absorption rate constant for Asian patients. Age, total protein, and smoking/alcohol history did not affect PK parameters. Predictive check plots were consistent with observed data, implying an adequate description of empagliflozin PKs following multiple dosing in patients with T2DM. The lack of marked covariate effects, including weight, suggests that no exposure-based dose adjustments were required within the study population and dose range.

journal_name

J Clin Pharmacol

authors

Riggs MM,Staab A,Seman L,MacGregor TR,Bergsma TT,Gastonguay MR,Macha S

doi

10.1002/jcph.147

subject

Has Abstract

pub_date

2013-10-01 00:00:00

pages

1028-38

issue

10

eissn

0091-2700

issn

1552-4604

journal_volume

53

pub_type

杂志文章,随机对照试验
  • Darunavir/ritonavir pharmacokinetics following coadministration with clarithromycin in healthy volunteers.

    abstract::This study investigated the steady-state pharmacokinetic interaction between the HIV protease inhibitor, darunavir (TMC114), administered with low-dose ritonavir (darunavir/ritonavir), and clarithromycin in HIV-negative healthy volunteers. In a 3-way crossover study, 18 individuals received darunavir/ritonavir 400/100...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章,随机对照试验

    doi:10.1177/0091270007309706

    authors: Sekar VJ,Spinosa-Guzman S,De Paepe E,De Pauw M,Vangeneugden T,Lefebvre E,Hoetelmans RM

    更新日期:2008-01-01 00:00:00

  • Trial treatment length optimization with an emphasis on disease progression studies.

    abstract::Optimal design has been used in the past mainly to optimize sampling schedules for clinical trials. Optimization on design variables other than sampling times has been published in the literature only once before. This study shows, as an example, optimization on the length of treatment periods to obtain reliable estim...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章

    doi:10.1177/0091270008329560

    authors: Hennig S,Nyberg J,Hooker AC,Karlsson MO

    更新日期:2009-03-01 00:00:00

  • Lack of interaction between lansoprazole and propranolol, a pharmacokinetic and safety assessment.

    abstract::Due to the prevalence of both gastrointestinal and cardiovascular diseases, it is likely that patients may be coprescribed gastric parietal cell proton pump inhibitors and beta-adrenergic antagonists. Therefore, the objectives of this phase I study were to assess the potential effects of the coadministration of lansop...

    journal_title:Journal of clinical pharmacology

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:10.1177/00912700022008856

    authors: Karol MD,Locke CS,Cavanaugh JH

    更新日期:2000-03-01 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

  • Pharmacokinetics and tolerability of intravenous trecovirsen (GEM 91), an antisense phosphorothioate oligonucleotide, in HIV-positive subjects.

    abstract::Trecovirsen, a 25-mer antisense phosphorothioate oligonucleotide targeted at the gag site of the HIV gene, was administered to HIV-positive volunteers as an i.v. infusion. Single doses ranged from 0.1 to 2.5 mg/kg in an ascending escalation in cohorts of 6 to 12 subjects. Plasma trecovirsen concentrations and pharmaco...

    journal_title:Journal of clinical pharmacology

    pub_type: 临床试验,杂志文章

    doi:10.1177/00912709922007552

    authors: Séréni D,Tubiana R,Lascoux C,Katlama C,Taulera O,Bourque A,Cohen A,Dvorchik B,Martin RR,Tournerie C,Gouyette A,Schechter PJ

    更新日期:1999-01-01 00:00:00

  • Central nervous system effects of HMG CoA reductase inhibitors: lovastatin and pravastatin on sleep and cognitive performance in patients with hypercholesterolemia.

    abstract::Sleep disturbances and decrements of daytime performance have been attributed to HMG-CoA reductase inhibitors. As a rule, lipophilic compounds more readily cross the blood-brain barrier and are more likely to affect central nervous system function. The authors compared the effects of lovastatin (40 mg), a lipophilic c...

    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.1552-4604.1994.tb01971.x

    authors: Kostis JB,Rosen RC,Wilson AC

    更新日期:1994-10-01 00:00:00

  • Clinical pharmacology of topiramate versus lamotrigine versus phenobarbital: comparison of efficacy and side effects using odds ratios.

    abstract::Clinical pharmacologists, neurologists, internists, and all health care givers must consider the efficacy, safety, and side effect profile of a given antiepileptic drug (AED) when determining which drug is best for a given patient. The first purpose of this paper is to address whether the "new" AEDs have advantages ov...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章

    doi:

    authors: Lathers CM,Schraeder PL,Claycamp HG

    更新日期:2003-05-01 00:00:00

  • Effect of high-dose aspirin on CYP2E1 activity in healthy subjects measured using chlorzoxazone as a probe.

    abstract::The authors evaluated the effect of high-dose aspirin at a therapeutic dose, using chlorzoxazone as a probe for CYP2E1 enzyme activity. In a randomized, open-label, 2-way crossover study, 10 healthy men were treated 3 times daily for 6 days with 1 g aspirin or placebo. On day 7, 1 dose of 400 mg chlorzoxazone was admi...

    journal_title:Journal of clinical pharmacology

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:10.1177/0091270005282635

    authors: Park JY,Kim KA,Park PW,Ha JM

    更新日期:2006-01-01 00:00:00

  • Effects of grapefruit juice on pharmacokinetic exposure to indinavir in HIV-positive subjects.

    abstract::The objective of this study was to determine the effects of double-strength grapefruit juice on gastric pH and systemic bioavailability of indinavir in HIV-infected subjects receiving indinavir. Fourteen HIV-infected subjects took 800 mg of indinavir with 6 ounces (180 ml) of water or double-strength grapefruit juice....

    journal_title:Journal of clinical pharmacology

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:10.1177/00912700122010140

    authors: Shelton MJ,Wynn HE,Hewitt RG,DiFrancesco R

    更新日期:2001-04-01 00:00:00

  • FDA evaluations using in vitro metabolism to predict and interpret in vivo metabolic drug-drug interactions: impact on labeling.

    abstract::Recent advances in in vitro metabolism methods have led to an improved ability to predict clinically relevant metabolic drug-drug interactions. To address the relationships of in vitro metabolism data and in vivo metabolism outcomes, the Office of Clinical Pharmacology and Biopharmaceutics in the Center for Drug Evalu...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章

    doi:10.1177/00912709922008515

    authors: Davit B,Reynolds K,Yuan R,Ajayi F,Conner D,Fadiran E,Gillespie B,Sahajwalla C,Huang SM,Lesko LJ

    更新日期:1999-09-01 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

  • Effects of protriptyline and perphenazine in neurotic depressed outpatients.

    abstract::A four-week comparison of protriptyline 10 mg three times a day and perphenazine 2 mg three times a day, alone and in combination, and a placebo in a group of nonpsychotic depressed outpatients showed no significant differences among any of the treatment groups after both two and four weeks, and a slight trend in favo...

    journal_title:Journal of clinical pharmacology

    pub_type: 临床试验,杂志文章

    doi:10.1002/j.1552-4604.1975.tb02382.x

    authors: Weinstock R,Fisher S,Spillane J,Ise C,Shaw D,Torop P

    更新日期:1975-08-01 00:00:00

  • Tecarfarin, a novel vitamin K reductase antagonist, is not affected by CYP2C9 and CYP3A4 inhibition following concomitant administration of fluconazole in healthy participants.

    abstract::Comparative pharmacokinetics of vitamin K epoxide reductase antagonists tecarfarin and warfarin were assessed before and after coadministration for 21 days of the CYP450 inhibitor fluconazole in a randomized, open-label, single-center drug interaction study. Twenty healthy adult participants were randomized 1:1 to rec...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章,随机对照试验

    doi:10.1177/0091270010370588

    authors: Bavisotto LM,Ellis DJ,Milner PG,Combs DL,Irwin I,Canafax DM

    更新日期:2011-04-01 00:00:00

  • Effect of low-dose omeprazole (20 mg daily) on the pharmacokinetics of multiple-dose atazanavir with ritonavir in healthy subjects.

    abstract::Atazanavir, a potent protease inhibitor of human immunodeficiency virus (HIV), exhibits pH-dependent solubility. Previous studies have indicated that coadministration with omeprazole 40 mg once daily significantly decreased atazanavir exposure by approximately 75%. Concomitant use of omeprazole and atazanavir is curre...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章,随机对照试验

    doi:10.1177/0091270010367651

    authors: Zhu L,Persson A,Mahnke L,Eley T,Li T,Xu X,Agarwala S,Dragone J,Bertz R

    更新日期:2011-03-01 00:00:00

  • Estimation of the elimination half-life of a drug at any serum concentration when the Km and Vmax of the drug are known: calculations and validation with phenytoin.

    abstract::A method of estimating the elimination half-life of a drug at any selected serum concentration when the Km and Vmax of that drug are known is described. The method was validated in six patients by determining their Km and Vmax values for phenytoin, using data obtained at two serum concentrations and then using the Km ...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章

    doi:10.1002/j.1552-4604.1987.tb03022.x

    authors: Browne TR,Greenblatt DJ,Evans JE,Szabo GK,Evans BA,Schumacher GE

    更新日期:1987-04-01 00:00:00

  • Efficacy and pharmacokinetics of adefovir dipivoxil liquid suspension in patients with chronic hepatitis B and renal impairment.

    abstract::The study evaluated whether a liquid suspension of adefovir dipivoxil (ADV) is effective and safe when dose adjusted based on varying degrees of renal impairment in patients with chronic hepatitis B. Patients had stable mild, moderate, or severe renal impairment or end-stage renal disease. Twenty-eight patients were e...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章,多中心研究

    doi:10.1177/0091270010381385

    authors: Shiffman ML,Pol S,Rostaing L,Schiff E,Thabut D,Zeuzem S,Zong J,Frederick D,Rousseau F

    更新日期:2011-09-01 00:00:00

  • Pharmacokinetics of high-dose abetimus sodium in normal subjects with specific assessment of effect on coagulation.

    abstract::Abetimus sodium is an oligonucleotide-based investigational drug designed to treat patients with lupus nephritis by specifically reducing anti-double-stranded DNA antibody levels. The safety and pharmacokinetics of abetimus were evaluated in 24 healthy volunteers at intravenous doses of 600 mg, 1200 mg, and 2400 mg. T...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章,随机对照试验

    doi:10.1177/0091270008319465

    authors: Linnik MD,O'Rourke AM,Crowther MA

    更新日期:2008-08-01 00:00:00

  • Efficacy and duration of action of procaterol, a new bronchodilator.

    abstract::Procaterol, a new beta-adrenergic agonist, was tested in two different doses in patients with reversible airway obstruction. Single oral doses of 0.05 or 0.1 mg produce an increase in measured expiratory flow rates, and the peak and duration of action are both dose related. Side effects reported during this one-day st...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章

    doi:10.1002/j.1552-4604.1982.tb02669.x

    authors: Zanetti CL,Rotman HH,Dresner AJ

    更新日期:1982-05-01 00:00:00

  • Sulindac kinetics and effects on renal function and prostaglandin excretion in renal insufficiency.

    abstract::The purpose of this study was to evaluate the pharmacokinetics of sulindac, a purported "renal sparing" nonsteroidal anti-inflammatory drug, and its effects on renal function and prostaglandin excretion in patients with reduced glomerular filtration rate. Twelve female patients (glomerular filtration rate 37 +/- 4 mL/...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章

    doi:10.1002/j.1552-4604.1989.tb03275.x

    authors: Klassen DK,Stout RL,Spilman PS,Whelton A

    更新日期:1989-11-01 00:00:00

  • Comparison of the stability, efficacy, and adverse effect profile of the innovator 0.005% latanoprost ophthalmic solution and a novel cyclodextrin-containing formulation.

    abstract::Recently, a new latanoprost ophthalmic solution containing cyclodextrins was developed. The purpose of the present work was to compare the stability, clinical efficacy, and adverse effect profile of this formulation with the innovator product. The innovator formulation was stable at 4 degrees C but exhibited degradati...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章,多中心研究,随机对照试验

    doi:10.1177/0091270006292626

    authors: Gonzalez JR,Baiza-Duran L,Quintana-Hau J,Tornero-Montaño R,Castaneda-Hernandez G,Ortiz M,Alarcon-Oceguera F,Beltran-Loustaunau M,Cortez-Gastelum M,Garcidueñas-Mejia J,Gomez-Bastar P,Jimenez-Roman J,Korder-Ortega V,Paczka-Zapata

    更新日期:2007-01-01 00:00:00

  • Long-term therapy with tolmetin in rheumatoid arthritis.

    abstract::Data from over 1000 patients with rheumatoid arthritis who received tolmetin sodium in double-blind and open studies have been pooled to assess long-term efficacy and safety. Duration of the studies was 12 weeks to 48 months. Mean age of patients was 54 years; ratio of males to females was 1:3. The results showed that...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章

    doi:10.1002/j.1552-4604.1983.tb02739.x

    authors: Ehrlich GE

    更新日期:1983-07-01 00:00:00

  • Pharmacokinetic and biopharmaceutic aspects of once daily treatment with metoprolol CR/ZOK: a review article.

    abstract::In the development of a new controlled release preparation and its subsequent assessment there are a number of factors that need to be considered both related to the drug itself and to the pharmaceutical preparation. This review describes the biopharmaceutical and pharmacokinetic properties of metoprolol CR/ZOK, a rec...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章,评审

    doi:10.1002/j.1552-4604.1990.tb03490.x

    authors: Sandberg A,Abrahamsson B,Regårdh CG,Wieselgren I,Bergstrand R

    更新日期:1990-02-01 00:00:00

  • Intravitreal Injection of a Rho-Kinase Inhibitor (Fasudil) for Recent-Onset Nonarteritic Anterior Ischemic Optic Neuropathy.

    abstract::This study evaluated the effects of intravitreal injection of fasudil (IVF), a Rho-kinase inhibitor, in cases of recent-onset nonarteritic anterior ischemic optic neuropathy (NAION). In this interventional case series, 13 eyes of 13 patients diagnosed with NAION within 14 days of onset were included. The affected eyes...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章

    doi:10.1002/jcph.655

    authors: Sanjari N,Pakravan M,Nourinia R,Esfandiari H,Hafezi-Moghadam A,Zandi S,Nakao S,Shah-Heidari MH,Jamali A,Yaseri M,Ahmadieh H

    更新日期:2016-06-01 00:00:00

  • Computerized extraction of electrocardiograms from continuous 12-lead holter recordings reduces measurement variability in a thorough QT study.

    abstract::Continuous Holter recordings are often used in thorough QT studies (TQTS), with multiple 10-second electrocardiograms (ECGs) visually selected around predesignated time points. The authors hypothesized that computer-automated ECG selection would reduce within-subject variability, improve study data precision, and incr...

    journal_title:Journal of clinical pharmacology

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:10.1177/0091270011430505

    authors: George S,Rodriguez I,Ipe D,Sager PT,Gussak I,Vajdic B

    更新日期:2012-12-01 00:00:00

  • Safety, pharmacokinetics, and antiretroviral activity of the potent, specific human immunodeficiency virus protease inhibitor nelfinavir: results of a phase I/II trial and extended follow-up in patients infected with human immunodeficiency virus.

    abstract::The safety, antiretroviral activity, and pharmacokinetic profile of nelfinavir, a potent and specific inhibitor of human immunodeficiency virus (HIV) protease, were assessed in a small open-label phase I/II dose-ranging study in protease inhibitor-naive HIV-positive men. A total of 22 patients with baseline plasma HIV...

    journal_title:Journal of clinical pharmacology

    pub_type: 临床试验,杂志文章

    doi:10.1002/j.1552-4604.1998.tb04814.x

    authors: Moyle GJ,Youle M,Higgs C,Monaghan J,Prince W,Chapman S,Clendeninn N,Nelson MR

    更新日期:1998-08-01 00:00:00

  • Medication errors: an analysis comparing PHICO's closed claims data and PHICO's Event Reporting Trending System (PERTS).

    abstract::Clinical pharmacologists are all dedicated to improving the use of medications and decreasing medication errors and adverse drug reactions. However, quality improvement requires that some significant parameters of quality be categorized, measured, and tracked to provide benchmarks to which future data (performance) ca...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章

    doi:

    authors: Benjamin DM,Pendrak RF

    更新日期:2003-07-01 00:00:00

  • Effects of carbidopa and entacapone on the metabolic fate of the norepinephrine prodrug L-DOPS.

    abstract:BACKGROUND:L-threo-3,4-dihydroxyphenylserine (L-DOPS), a norepinephrine (NE) prodrug, is investigational for orthostatic hypotension, which occurs commonly in Parkinson's disease. Adjunctive anti-parkinsonian drugs might interact with L-DOPS. We tested whether L-aromatic amino-acid decarboxylase inhibition by carbidopa...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章,随机对照试验

    doi:10.1177/0091270010363476

    authors: Goldstein DS,Holmes C,Sewell L,Pechnik S,Kopin IJ

    更新日期:2011-01-01 00:00:00

  • The Application of Physiologically Based Pharmacokinetic Modeling to Predict the Role of Drug Transporters: Scientific and Regulatory Perspectives.

    abstract::Transporters play an important role in drug absorption, disposition, and drug action. The evaluation of drug transporters requires a comprehensive understanding of transporter biology and pharmacology. Physiologically based pharmacokinetic (PBPK) models may offer an integrative platform to quantitatively evaluate the ...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章,评审

    doi:10.1002/jcph.740

    authors: Pan Y,Hsu V,Grimstein M,Zhang L,Arya V,Sinha V,Grillo JA,Zhao P

    更新日期:2016-07-01 00:00:00

  • Cholestyramine-induced hyperchloremic metabolic acidosis.

    abstract::Cholestyramine is a nonabsorbable anion exchange resin that is used predominantly for the treatment of hypercholesterolemia in adults and the management of acute diarrhea in children. The authors report two cases of severe hyperchloremic nonanion gap metabolic acidosis associated with the use of cholestyramine therapy...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章,评审

    doi:10.1177/009127009203200608

    authors: Scheel PJ Jr,Whelton A,Rossiter K,Watson A

    更新日期:1992-06-01 00:00:00

  • Pharmacokinetics, pharmacodynamics, and safety of a platelet GPIIb/IIIa antagonist, RGD891, following intravenous administration in healthy male volunteers.

    abstract::The pharmacokinetics (PK), pharmacodynamics (PD), and safety of a platelet GPIIb/IIIa receptor antagonist, RGD891, and its active metabolite, RGD039, were evaluated after administration of various intravenous regimens of RGD891 to healthy male volunteers in two Phase I studies. Plasma and urine concentrations of RGD89...

    journal_title:Journal of clinical pharmacology

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:

    authors: Zannikos PN,Rohatagi S,Jensen BK,DePhillips SL,Massignon D,Calic F,Sibille M,Kirkesseli S

    更新日期:2000-11-01 00:00:00