Abstract：
:The effect of telbivudine on cardiac repolarization was evaluated in healthy participants at clinical and supratherapeutic doses. Sixty-two participants were enrolled, stratified by sex, and randomized according to a crossover design among 4 treatment sequences: placebo, a single moxifloxacin 400-mg dose as positive calibrator, and telbivudine 600 and 1800 mg/d for 7 days. Intensive time-matched electrocardiogram measurements and pharmacokinetic sampling were performed at baseline and on day 7 over 24 hours. For telbivudine and moxifloxacin, time-matched, placebo-adjusted change from baseline in QT was calculated and corrected using Fridericia's formula (QTcF). While moxifloxacin produced the expected significant changes in QTcF, none of the changes in QTcF for either doses of telbivudine exceeded 5 ms, and none of the associated upper 1-sided 95% confidence intervals (CI) exceeded the limit of 10 ms. There was no increase in QTcF with increasing plasma telbivudine. The supratherapeutic dose of telbivudine was well tolerated with a safety profile similar to the clinical dose despite a 3-fold increase in plasma exposure. This study therefore met the criteria for a negative thorough QT study. Telbivudine had no adverse effect on cardiac repolarization in healthy participants, even at supratherapeutic exposure, suggesting a broad safety margin.
journal_name
J Clin Pharmacoljournal_title
Journal of clinical pharmacologyauthors
Poordad F,Zeldin G,Harris SI,Ke J,Xu L,Mayers D,Zhou XJdoi
10.1177/0091270009337943subject
Has Abstractpub_date
2009-12-01 00:00:00pages
1436-46issue
12eissn
0091-2700issn
1552-4604pii
0091270009337943journal_volume
49pub_type
杂志文章,随机对照试验abstract：:The need for clinical pharmacology in research and education, drug development, and health care delivery is well known. However, a current profile of those working in the field is not available. The ACCP authorized a survey of clinical pharmacologists to provide such a profile. Members of the ACCP or ASCPT were solici...
journal_title：Journal of clinical pharmacology
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journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
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journal_title：Journal of clinical pharmacology
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