Desirudin dosing and monitoring in moderate renal impairment.

Abstract:

:Desirudin is a renally eliminated direct thrombin inhibitor approved to prevent venous thromboembolism. Empiric dosage adjustment and activated partial thromboplastin time (aPTT) monitoring in patients with moderate renal impairment are recommended, but supportive data are lacking. The objective of this study was to evaluate appropriate desirudin dosing in moderate renal impairment and the effect of desirudin on aPTT in moderate renal impairment. Desirudin plasma concentration and aPTT data were extracted from 6 studies. Participants with normal renal function or moderate renal impairment (creatinine clearance [ClCr] 31-60 mL/min) were included. Pharmacokinetic and Monte Carlo simulations were done. After administration of desirudin 15 mg every 12 hours subcutaneously (SC) to steady state, peak desirudin concentrations were 35 and 47 nmol/L in the normal and moderate renal function groups, respectively. Monte Carlo simulations found median 2-hour C(max) concentrations of 51.7 nmol/L in normal renal function and 52.4 nmol/L in moderate renal impairment. Desirudin exhibits a linear relationship when the square root of desirudin concentration is plotted versus the aPTT ratio (r(2) = 0.76). These analyses support the dosing of desirudin at 15 mg every 12 hours SC without aPTT monitoring in patients with moderate renal impairment.

journal_name

J Clin Pharmacol

authors

Nafziger AN,Bertino JS Jr

doi

10.1177/0091270009350626

subject

Has Abstract

pub_date

2010-06-01 00:00:00

pages

614-22

issue

6

eissn

0091-2700

issn

1552-4604

pii

0091270009350626

journal_volume

50

pub_type

杂志文章
  • Dose proportionality and the effect of food on vildagliptin, a novel dipeptidyl peptidase IV inhibitor, in healthy volunteers.

    abstract::Vildagliptin is a potent and selective dipeptidyl peptidase IV inhibitor in development for the treatment of type 2 diabetes that improves glycemic control by enhancing alpha- and beta-cell responsiveness to glucose. Two open-label, single-dose, randomized, crossover studies in healthy subjects (ages 18-45 years) inve...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章,随机对照试验

    doi:10.1177/0091270007304313

    authors: Sunkara G,Sabo R,Wang Y,He YL,Campestrini J,Rosenberg M,Howard D,Dole WP

    更新日期:2007-09-01 00:00:00

  • Cytochrome P450 Genetic Variations Can Predict mRNA Expression, Cyclophosphamide 4-Hydroxylation, and Treatment Outcomes in Chinese Patients With Non-Hodgkin's Lymphoma.

    abstract::To investigate the impact of cytochrome P450 (CYP) genetic polymorphisms CYP2B6, CYP2C19, and CYP3A5 on mRNA expression, cyclophosphamide/4-hydroxycyclophosphamide pharmacokinetics, and treatment outcomes of the R-CHOP regimen (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) in Chinese patients ...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章

    doi:10.1002/jcph.878

    authors: Shu W,Chen L,Hu X,Zhang M,Chen W,Ma L,Liu X,Huang J,Pang T,Li J,Zhang Y

    更新日期:2017-07-01 00:00:00

  • Application of preclinical data to initiate the modified continual reassessment method for maximum tolerated dose-finding trials.

    abstract::This study was conducted to evaluate whether the allometric approach can be used to predict maximum tolerated dose (MTD) in humans from animal data. Twenty-five anticancer drugs were taken from the literature and used in this analysis. The results of the study indicate that MTD can be predicted with reasonable accurac...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章

    doi:10.1177/00912700122009791

    authors: Mahmood I

    更新日期:2001-01-01 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

  • Pharmacokinetics and acute safety of inhaled testosterone in postmenopausal women.

    abstract::This was a preliminary feasibility study to assess the pharmacokinetics and acute safety of a single dose of orally inhaled testosterone via the AERx system, a novel handheld aerosol delivery system in postmenopausal women. Twelve postmenopausal women stabilized on oral estrogen therapy were treated with a single dose...

    journal_title:Journal of clinical pharmacology

    pub_type: 临床试验,杂志文章

    doi:10.1177/0091270004269840

    authors: Davison S,Thipphawong J,Blanchard J,Liu K,Morishige R,Gonda I,Okikawa J,Adams J,Evans A,Otulana B,Davis S

    更新日期:2005-02-01 00:00:00

  • Pharmacokinetics of doripenem during high volume hemodiafiltration in patients with septic shock.

    abstract::Pharmacokinetics (PK) of doripenem was determined during high volume hemodiafiltration (HVHDF) in patients with septic shock. A single 500 mg dose of doripenem was administered as a 1 hour infusion during HVHDF to 9 patients. Arterial blood samples were collected before and at 30 or 60 minute intervals over 8 hours (1...

    journal_title:Journal of clinical pharmacology

    pub_type: 临床试验,杂志文章

    doi:10.1002/jcph.432

    authors: Tamme K,Oselin K,Kipper K,Low K,Standing JF,Metsvaht T,Karjagin J,Herodes K,Kern H,Starkopf J

    更新日期:2015-04-01 00:00:00

  • Long-duration +Gz acceleration on cardiac volumes determined by two-dimensional echocardiography.

    abstract::To enhance protection of humans exposed to long-duration low-gravity environments such as the Space Shuttle and National Aerospace Plane during re-entry or in the short-duration high(-)+Gz environment of fighter aircraft, the effects of +Gz acceleration on cardiovascular hemodynamics must be understood. This study rep...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章

    doi:10.1002/j.1552-4604.1994.tb04991.x

    authors: Tripp LD,Jennings TJ,Seaworth JF,Howell LL,Goodyear C

    更新日期:1994-05-01 00:00:00

  • Population pharmacokinetic and pharmacodynamic analyses from a 4-month intradose escalation and its subsequent 12-month dose titration studies for a human monoclonal anti-FGF23 antibody (KRN23) in adults with X-linked hypophosphatemia.

    abstract::X-linked hypophosphatemia (XLH) is an inherited metabolic bone disease with abnormally elevated serum FGF23 resulting in low renal maximum threshold for phosphate reabsorption, low serum phosphate (Pi) and 1,25-dihydroxyvitamin D levels with subsequent development of short stature and skeletal deformities. KRN23 is a ...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章

    doi:10.1002/jcph.611

    authors: Zhang X,Peyret T,Gosselin NH,Marier JF,Imel EA,Carpenter TO

    更新日期:2016-04-01 00:00:00

  • Therapeutic efficacy of a new anhydrous theophylline dosage form.

    abstract::A clinical study was performed on 41 asthmatic patients. After complete physical and spirometric examinations, they received capsules containing 200 mg anhydrous theophylline per capsule t.i.d. for three weeks. All other antiasthmatic medications were omitted during this study. The results showed that these capsules (...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章

    doi:10.1002/j.1552-4604.1976.tb01535.x

    authors: Miller J,Salem H

    更新日期:1976-07-01 00:00:00

  • Lofexidine in the treatment of hypertension: a twice-daily versus one-daily dose comparison with 24-hour blood pressure monitoring.

    abstract::Lofexidine, an antihypertensive imidazoline derivative, was given to ten hypertensives on both a twice-daily and once-daily regimen, using routine blood pressure measurements and 24-hour Remler recording. Plasma renin activity and catecholamines were measured. After a dose titration with twice-daily doses, the total t...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章

    doi:10.1002/j.1552-4604.1981.tb05697.x

    authors: Garrett BN,Kaplan NM

    更新日期:1981-04-01 00:00:00

  • A double-blind comparison of orally administered ciramadol and codeine for relief of postoperative pain.

    abstract::Ciramadol, a new analgesic with mixed narcotic agonist-antagonist actions, was compared with codeine and placebo in a double-blind study in 343 patients with postoperative pain. The patients received a single oral dose of either 30 or 60 mg of ciramadol, 60 mg of codeine, or placebo. As indicated by three efficacy mea...

    journal_title:Journal of clinical pharmacology

    pub_type: 临床试验,杂志文章

    doi:10.1002/j.1552-4604.1985.tb02882.x

    authors: Graf DF,Pandit SK,Kothary SP,Freeland GR

    更新日期:1985-11-01 00:00:00

  • Profile of clinical pharmacologists in the United States.

    abstract::The need for clinical pharmacology in research and education, drug development, and health care delivery is well known. However, a current profile of those working in the field is not available. The ACCP authorized a survey of clinical pharmacologists to provide such a profile. Members of the ACCP or ASCPT were solici...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章

    doi:10.1002/j.1552-4604.1989.tb03404.x

    authors: Wilson JT,Brown RD,Kimura KK,Whelton A

    更新日期:1989-08-01 00:00:00

  • Determination of cefalexin pharmacokinetics and dosage adjustments in relation to renal function.

    abstract::Following oral administration of a single 500-mg dose of cefalexin, serum and urine levels of the antibiotic were determined comparatively in ten normal subjects, ten patients with renal impairment, and ten patients with chronic nephritis on maintenance hemodialysis. In normal subjects, mean serum peak levels (12.0 +/...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章

    doi:10.1002/j.1552-4604.1975.tb05918.x

    authors: Brogard JM,Pinget M,Dorner M,Lavillaureix J

    更新日期:1975-10-01 00:00:00

  • Axitinib in metastatic renal cell carcinoma: results of a pharmacokinetic and pharmacodynamic analysis.

    abstract::Axitinib is a potent and selective inhibitor of vascular endothelial growth factor receptors 1, 2, and 3, approved for second-line therapy for advanced renal cell carcinoma (RCC). Axitinib population pharmacokinetic and pharmacokinetic/pharmacodynamic relationships were evaluated. Using nonlinear mixed effects modelin...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章

    doi:10.1002/jcph.73

    authors: Rini BI,Garrett M,Poland B,Dutcher JP,Rixe O,Wilding G,Stadler WM,Pithavala YK,Kim S,Tarazi J,Motzer RJ

    更新日期:2013-05-01 00:00:00

  • Primary care physicians and the cost of drugs: a study of prescribing practices based on recognition and information sources.

    abstract::Rapidly inflating health care costs limit patient care, and prescription drug costs constitute a major component of this expenditure. This study examines attitudes toward and knowledge of prescription drug costs of primary care physicians. Access to information about drug costs and implications for medical education a...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章

    doi:10.1002/j.1552-4604.1994.tb04726.x

    authors: Walzak D,Swindells S,Bhardwaj A

    更新日期:1994-12-01 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

  • Caffeine metabolism in premature infants.

    abstract::Caffeine has been used frequently in the treatment and prevention of apnea of prematurity. The metabolism of caffeine depends on the activities of the hepatic enzymes that vary from one infant to another. The objective of this study was to determine the influence of postnatal age (PNA), birth weight (BW), study weight...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章

    doi:10.1177/00912700122010500

    authors: al-Alaiyan S,al-Rawithi S,Raines D,Yusuf A,Legayada E,Shoukri MM,el-Yazigi A

    更新日期:2001-06-01 00:00:00

  • A phase-1, open-label, single-dose study of the pharmacokinetics of buparlisib in subjects with mild to severe hepatic impairment.

    abstract::The pharmacokinetics (PK) and safety of single-dose buparlisib (30 mg) were assessed in subjects with mild to severe hepatic impairment (n = 6 each) relative to healthy controls (n = 13). Blood samples were collected until 336 hours postdose and evaluated by liquid chromatography tandem mass spectrometry. PK parameter...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章

    doi:10.1002/jcph.590

    authors: Csonka D,Hazell K,Waldron E,Lorenzo S,Duval V,Trandafir L,Kobalava ZD

    更新日期:2016-03-01 00:00:00

  • Saturable first-pass kinetics of propranolol.

    abstract::Reduced bioavailability (F) due to hepatic first-pass extraction of an oral dose (D) is a well-known pharmacokinetic phenomenon. An integrated solution for Michaelis-Menten kinetics of the first-pass effect is derived from the maximal metabolic rate (Vm), volume of distribution (Vd), first order absorption rate consta...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章

    doi:10.1002/j.1552-4604.1989.tb03320.x

    authors: Keller F,Kunzendorf U,Walz G,Haller H,Offermann G

    更新日期:1989-03-01 00:00:00

  • Effects of ABT-761, a novel 5-lipoxygenase inhibitor, on the pharmacokinetics of a single dose of ethinyl estradiol and levonorgestrel in healthy female volunteers.

    abstract::ABT-761 is a second-generation 5-lipoxygenase inhibitor in clinical development for the treatment of asthma. The effects of ABT-761 on the pharmacokinetics of an oral contraceptive were assessed in 21 female adult volunteers in a phase I, multiple-dose, open-label study. Subjects received a single dose of oral contrac...

    journal_title:Journal of clinical pharmacology

    pub_type: 临床试验,杂志文章

    doi:10.1002/j.1552-4604.1998.tb04472.x

    authors: Wong SL,O'Dea RF,Dube LM,Awni WM

    更新日期:1998-07-01 00:00:00

  • Effects of esmolol on airway function in patients with asthma.

    abstract::In a double-blind, randomized, crossover study in ten patients with asthma, the effects on specific airway resistance of esmolol, a new ultra-short-acting beta 1-selective adrenoceptor blocker, were compared with those of placebo. Specific airway resistance was measured during increasing doses of esmolol infusion, dur...

    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.1552-4604.1986.tb02929.x

    authors: Sheppard D,DiStefano S,Byrd RC,Eschenbacher WL,Bell V,Steck J,Laddu A

    更新日期:1986-03-01 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

  • A Randomized Controlled Exploratory Pilot Study to Evaluate the Effect of Rotigotine Transdermal Patch on Parkinson's Disease-Associated Chronic Pain.

    abstract::Pain is a troublesome nonmotor symptom of Parkinson's disease (PD). This double-blind exploratory pilot study (NCT01744496) was the first to specifically investigate the effect of a dopamine agonist on PD-associated pain as primary outcome. Patients with advanced PD (ie, receiving levodopa) and at least moderate PD-as...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章,多中心研究,随机对照试验

    doi:10.1002/jcph.678

    authors: Rascol O,Zesiewicz T,Chaudhuri KR,Asgharnejad M,Surmann E,Dohin E,Nilius S,Bauer L

    更新日期:2016-07-01 00:00:00

  • Multiple doses of sitagliptin, a selective DPP-4 inhibitor, do not meaningfully alter pharmacokinetics and pharmacodynamics of warfarin.

    abstract::Sitagliptin is an orally active, highly selective dipeptidyl peptidase IV (DPP-4) inhibitor for treatment of type 2 diabetes mellitus. This randomized, open-label, 2-part, 2-period crossover study assessed pharmacokinetics/pharmacodynamics of warfarin in the presence/absence of multiple-dose sitagliptin. Twelve partic...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章,随机对照试验

    doi:10.1177/0091270009341653

    authors: Wright DH,Herman GA,Maes A,Liu Q,Johnson-Levonas AO,Wagner JA

    更新日期:2009-10-01 00:00:00

  • Clinical utility of ambulatory blood pressure monitoring in target organ complications and equipment choices.

    abstract::Although population studies have demonstrated a relationship between casual office blood pressures and target organ events, the variability of these blood pressure measurements for individual patients has generated an interest in the role of ambulatory blood pressure monitoring for defining the presence of hypertensio...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章,评审

    doi:10.1002/j.1552-4604.1992.tb05771.x

    authors: Prisant LM,Bottini PB,Carr AA

    更新日期:1992-07-01 00:00:00

  • Cannabinoids and the cholinergic system.

    abstract::delta 9-Tetrahydrocannabinol (THC) decreases EEG activation and causes slow waves in the cat. The EEG slow-wave activity is accompanied by a concomitant decrease in acetylcholine release from the neocortex. The findings suggest that THC depresses the brain stem activating system. Large doses of delta 8- and delta 9-TH...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章

    doi:10.1002/j.1552-4604.1981.tb02602.x

    authors: Domino EF

    更新日期:1981-08-01 00:00:00

  • Multiple-dose, linear, dose-proportional pharmacokinetics of retigabine in healthy volunteers.

    abstract::Retigabine, a first-in-class selective M-current potassium channel opener, is a novel antiepileptic compound currently in clinical development. The purpose of this randomized placebo-controlled study was to assess retigabine oral safety and pharmacokinetics in healthy male volunteers (N = 45). Subjects received one do...

    journal_title:Journal of clinical pharmacology

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:10.1177/00912700222011210

    authors: Ferron GM,Paul J,Fruncillo R,Richards L,Knebel N,Getsy J,Troy S

    更新日期:2002-02-01 00:00:00

  • Atorvastatin does not alter the anticoagulant activity of warfarin.

    abstract::Twelve patients chronically maintained on warfarin were administered 80 mg atorvastatin for 2 weeks. Mean prothrombin times decreased slightly, but only for the first few days of the two-week treatment period. Thus atorvastatin had no consistent effect on the anticoagulant activity of warfarin and adjustment in warfar...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章

    doi:10.1002/j.1552-4604.1997.tb04288.x

    authors: Stern R,Abel R,Gibson GL,Besserer J

    更新日期:1997-11-01 00:00:00

  • Inaccuracy of hourly sampled pH measurements in describing the effect of antisecretory drugs on circadian gastric acidity.

    abstract::This study was carried out in order to verify whether gastric pH measurements obtained with continuous monitoring are more accurate in assessing the pharmacodynamic properties of antisecretory drugs than those obtained with the traditional hourly nasogastric aspiration method. Accordingly, we compared the most commonl...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章

    doi:10.1002/j.1552-4604.1990.tb03437.x

    authors: Mela GS,Savarino V

    更新日期:1990-01-01 00:00:00

  • Phase 1 First-in-Human, Single- and Multiple-Ascending Dose, and Food Effect Studies to Assess the Safety, Tolerability, and Pharmacokinetics of Presatovir for the Treatment of Respiratory Syncytial Virus Infection.

    abstract::Respiratory syncytial virus (RSV)-associated respiratory tract infection is a leading cause of hospitalizations in infants for which no effective treatment exists. RSV infection is also an important cause of respiratory disease in adults and immunocompromised patients. Presatovir (GS-5806) is an orally bioavailable an...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章

    doi:10.1002/jcph.1112

    authors: German P,Xin Y,Chien JW,Weng W,Mackman R,Lewis SA,Meng A,Ling J,Mathias A

    更新日期:2018-08-01 00:00:00