Simplification of Imipenem Dosing by Removal of Weight-Based Adjustments.


:In patients with renal insufficiency, dose adjustments based on creatinine clearance and body weight have been a component of imipenem dosage instructions. The objective of the current analysis was to provide revised dosing recommendations by evaluating the impact of creatinine clearance and body weight on the pharmacokinetics of imipenem. A population pharmacokinetics model was developed with data from 465 patients and 3300 pharmacokinetic samples. Simulations provided data to support revision of the dosing recommendations to remove body weight-adjusted dosing, and the analysis formed the basis for updates that are reflected on the current imipenem label for both the United States and Europe. The optimized regimen provided an advantage in terms of improved target attainment at breakpoint minimum inhibitory concentration values of 1 and 2 μg/mL, as low-body-weight patients maintained >90% probability of target attainment compared to <90% probability of target attainment achieved with the previously approved regimen. It was concluded that additional dose adjustments for body weight were not necessary and the new scheme would simplify dosing while maintaining patient safety and efficacy.


J Clin Pharmacol


Lala M,Brown M,Kantesaria B,Walker B,Paschke A,Rizk ML




Has Abstract


2019-05-01 00:00:00












  • Intravenous torsemide as adjunctive therapy in patients with acute pulmonary edema.

    abstract::The safety and efficacy of intravenous (i.v.) torsemide as adjunctive therapy for acute cardiogenic pulmonary edema was evaluated. Thirteen patients were treated with i.v. torsemide and six patients, with i.v. furosemide, as a positive control. Doses of torsemide, 20 mg or 40 mg, and furosemide, 40 mg or 80 mg, were a...

    journal_title: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


    authors: Stringer KA,Watson W,Gratton M,Wolfe R

    更新日期:1994-11-01 00:00:00

  • The pharmacokinetics of doxylamine: use of automated gas chromatography with nitrogen-phosphorus detection.

    abstract::Sixteen healthy male volunteers received a single oral dose of 25 mg doxylamine succinate. Doxylamine concentrations in plasma were measured by a newly developed gas chromatographic methodology, utilizing direct alkaline extraction into hexane:isoamyl alcohol followed by concentration and autoinjection. Doxylamine kin...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章


    authors: Friedman H,Greenblatt DJ

    更新日期:1985-09-01 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


    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

  • 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


    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

  • Population pharmacokinetics of ceftaroline in patients with acute bacterial skin and skin structure infections or community-acquired bacterial pneumonia.

    abstract::Ceftaroline, the active form of ceftaroline fosamil, is a broad-spectrum cephalosporin antibiotic. A population pharmacokinetic (PPK) model for ceftaroline was developed in NONMEM® using data from 185 healthy subjects and 92 patients with acute bacterial skin and skin structure infection (ABSSSI). Data from 128 patien...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章,多中心研究,随机对照试验


    authors: Van Wart SA,Forrest A,Khariton T,Rubino CM,Bhavnani SM,Reynolds DK,Riccobene T,Ambrose PG

    更新日期:2013-11-01 00:00:00

  • Chenodeoxycholic acid and ursodeoxycholic acid effects in endogenous hypertriglyceridemias. A controlled double-blind trial.

    abstract::A double-blind controlled trial was carried out to compare the effects of chenodeoxycholic acid (CDCA), ursodeoxycholic acid (UDCA), and placebo on cholesterol and triglyceride levels in patients with endogenous hypertriglyceridemias. The dose of both bile acids was four 150-mg capsules day. Total serum cholesterol le...

    journal_title:Journal of clinical pharmacology

    pub_type: 临床试验,杂志文章


    authors: Carulli N,Ponz de Leon M,Podda M,Zuin M,Strata A,Frigerio G,Digrisolo A

    更新日期:1981-10-01 00:00:00

  • Pharmacokinetic and pharmacodynamic profiles of vapiprost, a selective, long-lasting thromboxane receptor antagonist, after single and multiple oral administration to healthy volunteers.

    abstract::A selective thromboxane A2 (TXA2) receptor blocking agent, vapiprost, was orally administered to healthy male Japanese volunteers to investigate the pharmacokinetic and pharmacodynamic properties. The time-profile of vapiprost concentration in plasma was determined and the effects of the drug on platelet aggregation i...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章


    authors: Uematsu T,Nagashima S,Mizuno A,Hirano K,Nakashima M

    更新日期:1991-09-01 00:00:00

  • Population pharmacokinetics of pomalidomide.

    abstract::A population pharmacokinetic (PPK) model of pomalidomide was developed and the influence of demographic and disease-related covariates on PPK parameters was assessed based on data from 6 clinical trials of pomalidomide (dose range, 0.5-10 mg) in healthy participants (n = 96) and patients with multiple myeloma (MM; n =...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章


    authors: Li Y,Xu Y,Liu L,Wang X,Palmisano M,Zhou S

    更新日期:2015-05-01 00:00:00

  • The relation of anticonvulsant drug levels to complete seizure control.

    abstract::This study was undertaken to determine the relationship of serum ACD levels to dosage in a group of patients who had been seizure free for at least two years. It demonstrated that some patients remain completely seizure free with DPH and/or phenobarbital serum concentrations which are well below the reported "optimal"...

    journal_title:Journal of clinical pharmacology

    pub_type: 临床试验,杂志文章


    authors: Feldman RG,Pippenger CE

    更新日期:1976-01-01 00:00:00

  • No Clinical Impact of CYP3A5 Gene Polymorphisms on the Pharmacokinetics and/or Efficacy of Maraviroc in Healthy Volunteers and HIV-1-Infected Subjects.

    abstract::Maraviroc is a C-C chemokine receptor type-5 antagonist approved for the treatment of HIV-1. Previous studies show that cytochrome P450 3A5 (CYP3A5) plays a role in maraviroc metabolism. CYP3A5 is subject to a genetic polymorphism. The presence of 2 functional alleles (CYP3A5*1/*1) confers the extensive metabolism phe...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章,多中心研究


    authors: Vourvahis M,McFadyen L,Nepal S,Valluri SR,Fang A,Fate GD,Wood LS,Marshall JC,Chan PLS,Nedderman A,Haynes J,Savage ME,Clark A,Smith KY,Heera J

    更新日期:2019-01-01 00:00:00

  • Effect of cyclosporine on the pharmacokinetics of aliskiren in healthy subjects.

    abstract::To explore the clinical relevance of inhibition of multidrug resistance transporter 1 and organic anion transporting polypeptide transporter, a drug-drug interaction study was conducted using aliskiren and cyclosporine. This was an open-label, single-sequence, parallel-group, single-dose study in healthy subjects. Sub...

    journal_title:Journal of clinical pharmacology

    pub_type: 临床试验,杂志文章


    authors: Rebello S,Compain S,Feng A,Hariry S,Dieterich HA,Jarugula V

    更新日期:2011-11-01 00:00:00

  • Development and Verification of a Body Weight-Directed Disease Trial Model for Glucose Homeostasis.

    abstract::Weight loss has been associated with improvement in insulin sensitivity. It is consequently a cornerstone in the management of type 2 diabetes mellitus (T2DM). However, the strictly quantitative relationship between weight loss, insulin sensitivity, and clinically relevant glucose homeostasis biomarkers as well as cha...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章


    authors: Farhan N,Gebert I,Xing Y,Wieser K,Lingineni K,Ma X,Chien JY,Garhyan P,Schmidt S

    更新日期:2021-02-01 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


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

    更新日期:2003-03-01 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


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

    更新日期:1992-06-01 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


    authors: Zanetti CL,Rotman HH,Dresner AJ

    更新日期:1982-05-01 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


    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

  • The Bial 10-2474 Phase 1 Study-A Drug Development Perspective and Recommendations for Future First-in-Human Trials.

    abstract::BIA 10-2474 (a fatty acid amide hydrolase inhibitor) was evaluated in a first-in-human phase 1 study in normal volunteers to assess safety/tolerability, pharmacokinetics, pharmacodynamics, and food effect. The dose-escalation process consisted of a single-ascending-dose phase (SAD) and multiple-ascending-dose phase (M...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章,评审


    authors: Chaikin P

    更新日期:2017-06-01 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


    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

  • Methyldopa does not alter the disposition of digoxin.

    abstract::To investigate whether methyldopa alters digoxin disposition, eight healthy subjects received methyldopa titrated to 250 mg t.i.d. or placebo in a double-blind, cross-over manner for 16 consecutive days, with 0.25 mg intravenous digoxin coadministered on day 5 and 0.25 mg oral digoxin on days 9 to 16. Digoxin concentr...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章


    authors: May CA,Vlasses PH,Rocci ML Jr,Rotmensch HH,Swanson BN,Tannenbaum RP,Ferguson RK,Abrams WB

    更新日期:1984-08-01 00:00:00

  • Cardiovascular responses to standing: effect of hydration.

    abstract::Many astronauts experience intolerance to orthostatic stress after space flight, despite the ingestion of salt tablets and water equivalent to 0.9% saline just before their return to Earth. Previous research indicates that the ingestion of 1.07% saline solution increased plasma volume more than did 0.9% saline. Theref...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章


    authors: Frey MA,Lathers C,Davis J,Fortney S,Charles JB

    更新日期:1994-05-01 00:00:00

  • Interaction between sulindac and warfarin: different results in normal subjects and in an unusual patient with a potassium-losing renal tubular defect.

    abstract::While sulindac failed to affect significantly warfarin-induced hypoprothrombinemia in normal male volunteers, it markedly prolonged prothrombin time in a patient with a renal tubular defect who had been anticoagulated with warfarin. This difference in individual response with respect to a drug interaction illustrates ...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章


    authors: Loftin JP,Vesell ES

    更新日期:1979-11-01 00:00:00

  • A Mechanism-Based Pharmacokinetic/Pharmacodynamic Model for Bococizumab, a Humanized Monoclonal Antibody Against Proprotein Convertase Subtilisin/Kexin Type 9, and Its Application in Early Clinical Development.

    abstract::Bococizumab (RN316/PF-04950615), a humanized monoclonal antibody, binds to secreted proprotein convertase subtilisin/kexin type 9 (PCSK9) and prevents its downregulation of low-density lipoprotein receptor, leading to improved clearance and reduction of low-density lipoprotein cholesterol (LDL-C) in plasma. A mechanis...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章


    authors: Udata C,Garzone PD,Gumbiner B,Joh T,Liang H,Liao KH,Williams JH,Meng X

    更新日期:2017-07-01 00:00:00

  • The application of stable isotopes to studies of drug bioavailability and bioequivalence.

    abstract::The increased availability of chemical intermediates and automated instrumentation has resulted in expanded use of stable isotopes for bioavailability and bioequivalence studies in recent years. Initially, stable isotopes were confined to the labeling of mass internal standard compounds for gas chromatography/mass spe...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章


    authors: Wolen RL

    更新日期:1986-07-01 00:00:00

  • Calcium channel blockade in experimental aminoglycoside nephrotoxicity.

    abstract::Calcium channel blocker therapy has proved protective in certain models of ischemic-induced acute renal failure. This effect may be related to the prevention of calcium influx into injured cells or by the vasodilatory effects of verapamil that may result in an improvement in renal blood flow. In the current study, the...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章


    authors: Watson AJ,Gimenez LF,Klassen DK,Stout RL,Whelton A

    更新日期:1987-08-01 00:00:00

  • Precision Oncology Medicine: The Clinical Relevance of Patient-Specific Biomarkers Used to Optimize Cancer Treatment.

    abstract::Precision medicine in oncology is the result of an increasing awareness of patient-specific clinical features coupled with the development of genomic-based diagnostics and targeted therapeutics. Companion diagnostics designed for specific drug-target pairs were the first to widely utilize clinically applicable tumor b...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章,评审


    authors: Schmidt KT,Chau CH,Price DK,Figg WD

    更新日期:2016-12-01 00:00:00

  • Displacement of bilirubin from albumin by indomethacin.

    abstract::The primary albumin binding site of indomethacin is remote from the bilirubin binding site. Indomethacin is, at most, a weak displacer of bilirubin at low serum drug concentrations. When administered at dosages less than 1 mg/kg, indomethacin would appear to be safe with respect to serum binding of bilirubin in premat...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章


    authors: Rasmussen LF,Ahlfors CE,Wennberg RP

    更新日期:1978-10-01 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


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

    更新日期:1975-10-01 00:00:00

  • Comparison of bronchial effects of nabilone and terbutaline in healthy and asthmatic subjects.

    abstract::The acute bronchomotor effect of nabilone, a synthetic cannabinoid compound, was compared to that of terbutaline sulfate and placebo in six healthy and six asthmatic subjects. Bronchodilation following nabilone was intermediate between that of terbutaline and placebo in the healthy subjects but was equivalent to place...

    journal_title:Journal of clinical pharmacology

    pub_type: 临床试验,杂志文章


    authors: Gong H Jr,Tashkin DP,Calvarese B

    更新日期:1983-04-01 00:00:00

  • Safety and tolerability of single intravenous doses of T cell modulatory peptide (TCMP-80) in healthy volunteers.

    abstract::T Cell Modulatory Peptide (TCMP-80), L-lysine-L-serine, is a synthetic dipeptide structurally related to a selected amino acid sequence in human immunoglobulin G. Based on in vitro and preclinical in vivo testing, TCMP-80 has immunomodulatory properties. This report describes the first administration of TCMP-80 to man...

    journal_title:Journal of clinical pharmacology

    pub_type: 临床试验,杂志文章,随机对照试验


    authors: Eldon MA,Smith RA,Leese PT,Daigle AE,Katz DV,Richieri SP

    更新日期:1990-04-01 00:00:00

  • Intense surveillance of adverse drug reactions. An analysis of 338 patients.

    abstract::A prospective study of adverse drug reactions was recently completed at the Clinical Pharmacology Unit of J. J. Group of Hospitals. 338 patients were included in this study, and adverse reactions were noted by a team of workers including a nurse and a physician. World Health Organization definitions were used to descr...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章


    authors: Vakil BJ,Kulkarni RD,Chabria NL,Chadha DR,Deshpande VA

    更新日期:1975-05-01 00:00:00