Pharmacokinetics and pharmacodynamics of three moxifloxacin dosage forms: implications for blinding in active-controlled cardiac repolarization studies.

Abstract:

:Moxifloxacin is used in thorough QT studies to assess sensitivity for detection of an increase in QTc. Moxifloxacin is usually over-encapsulated for blinding. However, there is concern that over-encapsulation alters its pharmacokinetics. In a 4-arm, randomized crossover study, 22 volunteers received over-encapsulated moxifloxacin, over-encapsulated placebo, bare moxifloxacin, and intravenous (IV) moxifloxacin. Placebo capsules and IV infusions were administered so that treatments in each arm, except for bare moxifloxacin, were indistinguishable. Pharmacokinetics of the oral treatments were found to be nearly identical and to meet Food and Drug Administration criteria for bioequivalency. Relative to the IV infusion administered over 1 hour, the tablet formulation was bioequivalent to total exposure but not peak exposure maximum plasma concentration, which was lower by 22%. Median time to maximum plasma concentration of the IV infusion was 1.00 hour. A 2-compartment model with oral absorption and linear elimination adequately described the observed moxifloxacin data. Changes in QTcF mirrored the pharmacokinetic changes, and there was a linear relationship between plasma concentration of moxifloxacin and change in QTcF. A 2-stage infusion scheme for IV moxifloxacin mimics the oral plasma concentration versus time curve. Over-encapsulation of moxifloxacin did not alter its peak or total systemic exposures or pharmacodynamics after oral administration.

journal_name

J Clin Pharmacol

authors

Mason JW,Florian JA Jr,Garnett CE,Moon TE,Selness DS,Spaulding RR

doi

10.1177/0091270009356298

subject

Has Abstract

pub_date

2010-11-01 00:00:00

pages

1249-59

issue

11

eissn

0091-2700

issn

1552-4604

pii

0091270009356298

journal_volume

50

pub_type

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