Safety, tolerability and pharmacokinetics after single and multiple doses of preladenant (SCH420814) administered in healthy subjects.
What is known and Objective: Preladenant (SCH420814, MK-3814) is a highly selective orally bioavailable non-methylxanthine adenosine 2A (A2A) receptor antagonist under investigation for the treatment for Parkinson's disease. This study evaluated the safety, tolerability and pharmacokinetics of prela...
| Published in: | Journal of Clinical Pharmacy & Therapeutics Vol. 37; no. 5; pp. 578 - 588 |
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| Main Authors: | , , |
| Format: | research tables/charts randomized controlled trial Journal Article |
| Published: |
Wiley-Blackwell
Oct2012
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| Online Access: | View this record in EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=104502035&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 104502035 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 02694727 EV4 jtl: Journal of Clinical Pharmacy & Therapeutics issn: 02694727 maglogo: Y pubinfo: dt: Oct2012 vid: 37 iid: 5 pid: 480 pub: Wiley-Blackwell place: Malden, Massachusetts artinfo: ui: 104502035 79613601 10.1111/j.1365-2710.2012.01349.x NLM22676397 104502035 ppf: 578 ppct: 10 formats: fmt: @attributes: type: P tig: atl: Safety, tolerability and pharmacokinetics after single and multiple doses of preladenant (SCH420814) administered in healthy subjects. aug: au: Cutler, D. L. Tendolkar, A. Grachev, I. D. affil: Merck Sharp and Dohme Corp., Whitehouse Station, NJ sug: subj: Receptors, Cell Surface Antagonists and Inhibitors Drugs, Investigational Pharmacokinetics Drugs, Investigational Adverse Effects Drugs, Investigational Administration and Dosage Parkinson Disease Drug Therapy Human Randomized Controlled Trials Random Assignment Double-Blind Studies Male Adolescence Adult Middle Age Chromatography, Liquid Methods Mass Spectrometry Methods Data Analysis Software Descriptive Statistics Analysis of Variance Funding Source Adolescent: 13-18 years Adult: 19-44 years Middle Aged: 45-64 years Male ab: What is known and Objective: Preladenant (SCH420814, MK-3814) is a highly selective orally bioavailable non-methylxanthine adenosine 2A (A2A) receptor antagonist under investigation for the treatment for Parkinson's disease. This study evaluated the safety, tolerability and pharmacokinetics of preladenant at single and multiple doses for the first time in humans. Methods: These were two randomized, double-blind, placebo-controlled, ascending-dose studies, one evaluating single rising preladenant doses (5-200 mg) compared with placebo and the other evaluating multiple rising preladenant doses (10-200 mg once daily over 10 days) compared with placebo. Safety was the primary end point of both studies. Safety evaluations, physical examinations, electrocardiograms, vital signs determinations and routine laboratory tests were performed before and at intervals throughout the studies. Blood samples were collected immediately before study drug administration and at various time points after dosing. Pharmacokinetic assessments of plasma preladenant and metabolites SCH434748 and SCH446637 were performed. Results and Discussion: One hundred and eight healthy adult men were randomly assigned in a 3 : 1 ratio to receive oral preladenant or matching placebo capsules under fasting conditions. Preladenant reached peak plasma concentrations in ∼1 h and then declined rapidly. Dose-related increases in exposure were observed up to 100 mg/day; accumulation was negligible at all doses. Transient mild increases in blood pressure occurred within a few hours after preladenant administration; blood pressure changes were neither cumulative nor dose-related nor associated with clinical sequelae. What is new and Conclusion: Preladenant was generally well tolerated up to the maximum dose tested (200 mg/day). pubtype: Academic Journal doctype: research tables/charts randomized controlled trial Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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