Giuseppe
Emeritus
[Source: Antimicrobial Agents and Chemotherapy, full page: (LINK). Abstract, edited.]
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Tigecycline Does Not Prolong QTc Intervals in Healthy Subjects
Joan M. Korth-Bradley 1,#, Paul C. McGovern 1, Joanne Salageanu 2, Kyle Matschke 1, Anna Plotka 1 and Sylvester Pawlak 3
Author Affiliations: <SUP>1</SUP>Pfizer Inc., Collegeville, PA, USA <SUP>2</SUP>Pfizer Inc., Groton, CT, USA <SUP>3</SUP>Pfizer Inc., New Haven, CT, USA
ABSTRACT
We evaluated the effect of tigecycline (50 mg and 200 mg doses) on QTc intervals and assessed safety and tolerability in a randomized, placebo-controlled, four-period crossover study of 48 (44 male) healthy volunteers aged 22?53 years. Fed subjects received tigecycline 50 mg or 200 mg, or placebo in a blinded fashion or an open-label oral dose of moxifloxacin 400 mg after 1 L of intravenous fluid. Serial electrocardiograms were recorded before, and for 96 H after, dosing. Blood samples for tigecycline pharmacokinetics were collected after each recording. QTc intervals were corrected using Fridericia?s correction (QTcF). Pharmacokinetic parameters were calculated using noncompartmental methods with potential relationships examined using linear mixed-effects modeling. Adverse events were recorded. The upper limits of the 90% confidence interval for the mean difference between both tigecycline doses and placebo for all time-matched QTcF interval changes from baseline were <5 ms. Tigecycline concentrations initially declined rapidly and then more slowly. Pharmacokinetic means were: C<SUB>max</SUB> 432 ng/mL, AUC<SUB>0-inf</SUB> 2366 ng.H/mL, CL 21.1 L/H, V<SUB>ss</SUB> 610 L, and t<SUB>?</SUB> 22.1 H in the 50 mg group; and proportional or similar values were found for the 200 mg group. Linear mixed-effects modeling failed to show an effect on QTcF values by tigecycline concentrations (P = 0.755). Tigecycline does not prolong the QTc interval in healthy subjects.
FOOTNOTES
#Corresponding author: Joan Korth-Bradley, PharmD, PhD, Senior Director, Clinical Pharmacology, Pfizer Inc., Specialty Care Business Unit Collegeville, PA 19426 USA, Phone: +1 484 865 2914, Fax: +1 484 865 6450, E-mail: Joan.Korth-Bradley@pfizer.com
Copyright ? 2013, American Society for Microbiology. All Rights Reserved.
-Joan M. Korth-Bradley 1,#, Paul C. McGovern 1, Joanne Salageanu 2, Kyle Matschke 1, Anna Plotka 1 and Sylvester Pawlak 3
Author Affiliations: <SUP>1</SUP>Pfizer Inc., Collegeville, PA, USA <SUP>2</SUP>Pfizer Inc., Groton, CT, USA <SUP>3</SUP>Pfizer Inc., New Haven, CT, USA
ABSTRACT
We evaluated the effect of tigecycline (50 mg and 200 mg doses) on QTc intervals and assessed safety and tolerability in a randomized, placebo-controlled, four-period crossover study of 48 (44 male) healthy volunteers aged 22?53 years. Fed subjects received tigecycline 50 mg or 200 mg, or placebo in a blinded fashion or an open-label oral dose of moxifloxacin 400 mg after 1 L of intravenous fluid. Serial electrocardiograms were recorded before, and for 96 H after, dosing. Blood samples for tigecycline pharmacokinetics were collected after each recording. QTc intervals were corrected using Fridericia?s correction (QTcF). Pharmacokinetic parameters were calculated using noncompartmental methods with potential relationships examined using linear mixed-effects modeling. Adverse events were recorded. The upper limits of the 90% confidence interval for the mean difference between both tigecycline doses and placebo for all time-matched QTcF interval changes from baseline were <5 ms. Tigecycline concentrations initially declined rapidly and then more slowly. Pharmacokinetic means were: C<SUB>max</SUB> 432 ng/mL, AUC<SUB>0-inf</SUB> 2366 ng.H/mL, CL 21.1 L/H, V<SUB>ss</SUB> 610 L, and t<SUB>?</SUB> 22.1 H in the 50 mg group; and proportional or similar values were found for the 200 mg group. Linear mixed-effects modeling failed to show an effect on QTcF values by tigecycline concentrations (P = 0.755). Tigecycline does not prolong the QTc interval in healthy subjects.
FOOTNOTES
#Corresponding author: Joan Korth-Bradley, PharmD, PhD, Senior Director, Clinical Pharmacology, Pfizer Inc., Specialty Care Business Unit Collegeville, PA 19426 USA, Phone: +1 484 865 2914, Fax: +1 484 865 6450, E-mail: Joan.Korth-Bradley@pfizer.com
Copyright ? 2013, American Society for Microbiology. All Rights Reserved.
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