title: Electrocardiographic QTc changes due to moxifloxacin infusion.
abstract: Moxifloxacin (400-mg single dose) is a frequent positive control in thorough QT/QTc studies. This investigation assessed baseline and placebo-controlled QTc changes (DeltaDeltaQTc, individualized correction for heart rate and rate hysteresis) at 126 data points before, during, and after 1-hour moxifloxacin infusion in 44 healthy participants and in their sex-, race-, and age-defined subgroups. Constant linear DeltaDeltaQTc increase was found during the infusion. The postinfusion peak DeltaDeltaQTc values (corresponding to maximum plasma levels) were not statistically different in women (16.1 +/- 6.5 ms) and men (15.1 +/- 5.3 ms), Africans (15.3 +/- 5.3 ms) and whites (15.6 +/- 6.6 ms), and participants younger (16.5 +/- 4.8 ms) and older (14.7 +/- 6.6 ms) than the median age of 35 years. The DeltaDeltaQTc values were different in participants with a body mass index (BMI) below (16.8 +/- 5.4 ms) and above 30 kg/m(2) (10.8 +/- 5.1 ms; P = .008). Although the population mean DeltaDeltaQTc changes closely followed mean plasma-level kinetics (4.8 ms per 1 microg/mL), the individual postinfusion peak DeltaDeltaQTc was not related to individual peak plasma levels (P = NS) but was strongly related to BMI (P = .0007). Thus, the individual pharmacokinetic/pharmacodynamic effects are substantially variable; obese participants should be excluded from thorough QT/QTc studies.
authors.affiliation: St. Paul's Cardiac Electrophysiology, London, 16 Verulam Avenue, Purley, Surrey CR8 3NQ, England, UK. marek.malik@btinternet.com
authors.forename: Marek
authors.initials: M
authors.lastname: Malik
authors.forename: Katerina
authors.initials: K
authors.lastname: Hnatkova
authors.forename: Anna
authors.initials: A
authors.lastname: Schmidt
authors.forename: Peter
authors.initials: P
authors.lastname: Smetana
mesh_terms: D000328:Adult; D001372:Aza Compounds / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D015992:Body Mass Index; D004562:Electrocardiography / Q000187:drug effects*; D005260:Female; D024841:Fluoroquinolones; D006321:Heart / Q000187:drug effects*; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D000077266:Moxifloxacin; D011804:Quinolines / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D055815:Young Adult
chemical_list: D001372:Aza Compounds; D024841:Fluoroquinolones; D011804:Quinolines; D000077266:Moxifloxacin