Population pharmacokinetics of ABT-594 in subjects with diabetic peripheral neuropathic pain.
What is known and Objective: ABT-594 is a non-opioid, non-NSAID analgesic. The objective of this work was to characterize the population pharmacokinetics of ABT-594 in subjects with neuropathic pain. Methods: Efficacy, safety and pharmacokinetics of ABT-594 in subjects with painful diabetic polyneur...
| Publicado en: | Journal of Clinical Pharmacy & Therapeutics Vol. 37; no. 4; pp. 475 - 481 |
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| Autores principales: | , |
| Formato: | research tables/charts Journal Article |
| Publicado: |
Wiley-Blackwell
Aug2012
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=104470798&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 104470798 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 02694727 EV4 jtl: Journal of Clinical Pharmacy & Therapeutics issn: 02694727 maglogo: Y pubinfo: dt: Aug2012 vid: 37 iid: 4 pid: 480 pub: Wiley-Blackwell place: Malden, Massachusetts artinfo: ui: 104470798 77499278 10.1111/j.1365-2710.2011.01325.x NLM22145610 104470798 ppf: 475 ppct: 6 formats: fmt: @attributes: type: P tig: atl: Population pharmacokinetics of ABT-594 in subjects with diabetic peripheral neuropathic pain. aug: au: Dutta, S. Awni, W. affil: Department of Clinical Pharmacokinetics and Pharmacodynamics, Abbott, IL; Clinical Pharmacology and Pharmacometrics, Global Pharmaceutical Research and Development, Abbott, IL, USA sug: subj: Diabetic Neuropathies Drug Therapy Analgesics Pharmacokinetics Heterocyclic Compounds Pharmacokinetics Pyridines Pharmacokinetics Chronic Pain Drug Therapy Treatment Outcomes Analgesics Administration and Dosage Analgesics Blood Data Analysis Software Descriptive Statistics Models, Statistical Parametric Statistics Analysis of Covariance Human Male Female Nonparametric Statistics Random Sample Adult Middle Age Aged Aged, 80 and Over Adult: 19-44 years Middle Aged: 45-64 years Aged: 65+ years Aged, 80 & over Male Female ab: What is known and Objective: ABT-594 is a non-opioid, non-NSAID analgesic. The objective of this work was to characterize the population pharmacokinetics of ABT-594 in subjects with neuropathic pain. Methods: Efficacy, safety and pharmacokinetics of ABT-594 in subjects with painful diabetic polyneuropathy were evaluated in a randomized, double-blind, placebo-controlled, parallel-group, multi-centre, 7-week Phase 2 study. Subjects ( N = 266) were approximately equally divided into four groups to receive BID regimens of placebo or 150, 225 and 300 μg of ABT-594. ABT-594 concentrations were determined from all subjects, whereas a subset of subjects provided intensive pharmacokinetic samples on two occasions. One- and two-compartment models were explored for characterizing plasma ABT-594 concentration-time profiles. The relative importance of covariates (age, weight, body surface area, creatinine clearance, gender, nicotine use and albumin concentrations) was examined by use of the likelihood ratio test. Model building was accomplished using stepwise forward selection ( P < 0·05) and backward elimination ( P < 0·005) of covariates. Population analyses were performed using NONMEM. Results and Discussion: Optimal characterization of the plasma concentration data was achieved using a one-compartment base model. Creatinine clearance and age were found to be significant covariates in the forward selection process; backward elimination process identified only creatinine clearance as a significant covariate. What is new and Conclusion: A population pharmacokinetic model was developed to characterize ABT-594 concentrations in subjects with neuropathic pain. As ABT-594 is primarily eliminated as unchanged drug in the urine, creatinine clearance and age were significant covariates of clearance with creatinine clearance being the optimal predictor of ABT-594 clearance. pubtype: Academic Journal doctype: research tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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