Levocetirizine does not prolong the QT/QTc interval in healthy subjects: Results from a thorough QT study

European Journal of Clinical Pharmacology

Volumn 63, Issue 11, 2007, Pages 1011-1017

  Hulhoven, Réginald ^a   Rosillon, Dominique ^a   Letiexhe, Michel ^b   Meeus, Marie Anne ^a   Daoust, Agnès ^a   Stockis, Armel ^a  

^a UCB PHARMA   (Belgium)

^b UNIVERSITY OF LIÈGE   (Belgium)

Author keywords

ICH E14 guideline; Levocetirizine; QT QTc interval; Thorough QT study

Indexed keywords

LEVOCETIRIZINE; MOXIFLOXACIN; PLACEBO;

ADULT; ARTICLE; CLINICAL TRIAL; CONTROLLED CLINICAL TRIAL; CONTROLLED STUDY; CROSSOVER PROCEDURE; DOUBLE BLIND PROCEDURE; DRUG BLOOD LEVEL; DRUG EFFECT; ELECTROCARDIOGRAM; FEMALE; HEART RATE; HEART REPOLARIZATION; HOLTER MONITORING; HUMAN; HUMAN EXPERIMENT; MALE; NORMAL HUMAN; PRIORITY JOURNAL; QT INTERVAL; QTC INTERVAL; RANDOMIZED CONTROLLED TRIAL; SINGLE DRUG DOSE;

ADOLESCENT; ADULT; AZA COMPOUNDS; CETIRIZINE; CROSS-OVER STUDIES; DOSE-RESPONSE RELATIONSHIP, DRUG; DOUBLE-BLIND METHOD; ELECTROCARDIOGRAPHY, AMBULATORY; FEMALE; HEART RATE; HISTAMINE H1 ANTAGONISTS, NON-SEDATING; HUMANS; LONG QT SYNDROME; MALE; MIDDLE AGED; PIPERAZINES; QUINOLINES;

EID: 35248869253     PISSN: 00316970     EISSN: None     Source Type: Journal    
DOI: 10.1007/s00228-007-0366-5     Document Type: Article

References (26)

1. Devalia JL, De Vos C, Hanotte F, Baltes E (2001) A randomized, double-blind, crossover comparison among cetirizine, levocetirizine, and UCB 28557 on histamine-induced cutaneous responses in healthy adult volunteers. Allergy 56:50-57
2. Wang DY, Hanotte F, De Vos C, Clement P (2001) Effect of cetirizine, levocetirizine, and dextrocetirizine on histamine-induced nasal response in healthy adult volunteers. Allergy 56:339-343
3. Baltes E, Coupez R, Giezek H, Voss G, Meyerhoff C, et al (2001) Absorption and disposition of levocetirizine, the eutomer of cetirizine, administered alone or as cetirizine to healthy volunteers. Fundam Clin Pharmacol 15:269-277
4. Strolin-Benedetti M, Plisnier M, Kaise J, Maier L, Baltes E, et al (2001) Absorption, distribution, metabolism and excretion of [14C] levocetirizine, the R enantiomer of cetirizine, in healthy volunteers. Eur J Clin Pharmacol 57:571-582
5. Paakkari I (2002) Cardiotoxicity of new antihistamines and cisapride (review article). Toxicol Lett 127:279-284
6. ICH Guidance (2005) Clinical evaluation of QT/QTc interval prolongation and proarrhythmic potential for non-antiarrhythmic drugs. E14, Step 4, ICH Steering Committee
7. Morganroth J (2001) Focus on issues in measuring and interpreting changes in the QTc interval duration. Eur Heart J [Suppl 3]:K105-K111
8. Morganroth J (2004) A definitive or thorough Phase 1 QT ECG trial as a requirement for drug safety assessment. J Electrocardiol 37:25-29
9. Darpo B, Nebout T, Sager PT (2006) Clinical evaluation of QT/QTc prolongation and proarrhythmic potential for nonantiarrhythmic drugs. In: Int 9th Conf Harmonization Tech Requirements Registration Pharmaceuticals Human Use E14 Guideline. J Clin Pharmacol 46:498-507
10. Grisanti S, Morganroth J, Shah RR (2005) A practical approach to cardiac safety: Implementing ICH E14 to define cardiac safety in new drug development. Appl Clin Trials Suppl October 2005, pp 10-16
11. Patterson SD (on behalf of Pharmaceutical Research and Manufacturers of America QT Statistics Expert Team) (2005) Investigating drug-induced QT and QTc prolongation in the clinic: A review of statistical design and analysis considerations. Drug Inf J 39:243-266
12. Shah RR (2005) Drugs, QTc interval prolongation and final ICH E14 guideline: An important milestone with challenges ahead. Drug Safety 28:1009-1028
13. Sale ME, Barbey JT, Woosley RL, Edwards D, Yeh J, et al (1994) The electrocardiographic effects of cetirizine in normal subjects. Clin Pharmacol Ther 56:295-301
14. Hussein Z, Pitsiu M, Aarons L et al (2005) Retrospective population pharmacokinetics of levocetirizine in atopic children receiving cetirizine: the ETAC study. Br J Clin Pharmacol 59:28-37
15. Williams GC, Dunnington KM, Hu MY, Zimmerman TR Jr, Wang Z, Hafner KB, et al (2006) The impact of posture on cardiac repolarization: more than heart rate? J Cardiovasc Electrophysiol 17:352-358
16. Stass H, Dalhoff A, Kubitza D, Schuhly U (1998) Pharmacokinetics, safety, and tolerability of ascending single doses of moxifloxacin, a new 8-methoxy quinolone, administered to healthy subjects. Antimicrob Agents and Chemother 42:2060-2065
17. Stass H, Kubitza D, Schuhly U (2001) Pharmacokinetics, safety and tolerability of moxifloxacin, a novel 8-methoxyfluoroquinolone, after repeated oral administration. Clin Pharmacokinet 40[Suppl1]:1-9
18. Sullivan JT, Woodruff M, Lettieri J, Agarwal V, Krol GJ, Leese PT, et al (1999) Pharmacokinetics of a once-daily oral dose of moxifloxacin (Bay 12-8039), a new enantiomerically pure 8-methoxy quinolone. Antimicrob Agents Chemother 43:2793-2797
19. Monahan BP, Ferguson CL, Killeavy ES, Lloyd BK, Troy J, Cantelina LR (1990) Torsades de pointes occurring in association with terfenadine use. JAMA 264:2788-2790
20. Honig PK, Wortham DC, Zamani K, Conner DP, Mullin JC, Cantelina LR (1993) Terfenadine-ketoconazole interaction: pharmacokinetic and electrocardiographic consequences. JAMA 269:1513-1518
21. DuBuske LM (1999) Second-generation antihistamines: the risk of ventricular arrhythmias. Clin Ther 21:281-295
22. Morganroth J (2007) Cardiac repolarization and the safety of new drugs defined by electrocardiography. Clin Pharmacol Ther 81:108-113
23. Sun H (2007) Pharmacometric methods for assessing drug-induced QT and QTc prolongations for non-antiarrhythmic drugs. In: Ette EI, Williams PJ (eds) Pharmacometrics: the science of quantitative pharmacology. John Wileys & Sons, New York, pp 977-992
24. Skerjanec A, Affrime MB, Milosavljev S, et al (2005) Darifenacin, an M3 selective receptor antagonist (M3 SAR), does not prolong QT/QTc. Clin Pharmacol Ther 79:P10
25. Harris SC, Hoelscher D, Krisensen A, O'Keefe SA, et al (2005) Effect of buprenorphine transdermal system 10 mg and 2∈×∈20 mg on QT intervals in healthy subjects. Clin Pharmacol Ther 79:P35
26. Noel GJ, Natarajan J, Chien S, Hunt TL, Goodman DB, Abels R (2003) Effects of three fluoroquinolones on QT interval in healthy adults after single doses. Clin Pharmacol Ther 73:292-303