DoseFinding Study of Landiolol Hydrochloride A S

Authors: Masaharu Hirano Kazuhiro Hara Yuji Ikari Masahiro Jinzaki Misako Iino Chikuma Hamada Sachio Kuribayashi

Publish Date: 2013/09/24

Volume: 30, Issue: 9, Pages: 803-818

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Abstract

Coronary computedtomography angiography CCTA has high diagnostic performance but it sometimes does not allow evaluation because of artifacts Currently the use of a βblocker is recommended to prevent motion artifacts but the βblocker metoprolol propranolol etc commonly used has a slow onset and long duration of action Landiolol hydrochloride is an intravenous β1blocker with a very short halflife We investigated the efficacy and optimal dose of this drug for reduction of heart rate in patients undergoing CCTAEightyseven subjects with ischemic heart disease were divided into three groups to receive landiolol hydrochloride at a dose of 0125 Group L 025 Group M or 05 mg/kg Group H CCTA was performed at 3–7 min after administration and heart rate blood pressure and image quality were assessedHeart rate decreased rapidly after completion of landiolol hydrochloride administration in all groups with a heart rate reduction of 1555 ± 656 in Group L 1648 ± 780 in Group M and 2149 ± 613 in Group H Group L vs Group H P = 00008 Group M vs Group H P = 00109 Since there was no significant difference in heart rate during imaging among the three groups although there was a significant difference between groups L and H and groups M and H in terms of percent change in heart rate coronary stenosis was diagnosable in all groups with no significant differenceLandiolol hydrochloride showed a rapid onset and short βblocking effect and was most effective at a dose of 05 mg/kg However the diagnosable proportion had no significant differences among the three groups in CCTA Therefore the clinically recommended dose was 0125 mg/kg or less considering the heart rate of patients with suspected coronary stenosis during CCTACoronary angiography CAG has been used for the diagnosis of coronary stenosis or occlusion which causes ischemic heart disease including angina pectoris and acute myocardial infarction With the development of medical devices marked progress has been made recently in noninvasive diagnostic imaging In particular coronary computedtomography angiography CCTA using multidetector row computed tomography MDCT has proved to be an excellent imaging modality for the diagnosis of cardiovascular disease as it not only has high spatial resolution but also allows imaging with only one breath hold 1 2 3 Using a noninvasive approach CCTA provides morphological information equivalent to that obtained by CAG and also has very high diagnostic performance for cardiovascular disease However although CCTA has high diagnostic performance in clinical settings it does not allow assessment in some patients because of artifacts associated with calcification beamhardening effect or the influence of heart beat motion artifact 4 5 6 Solutions to these artifacts have been sought and attempts have been made to eliminate artifacts due to calcification using dual energy 7 8 or subtraction 9 10 11 As well as eliminating motion artifacts sufficient time resolution is required to visualize the beating heart in a resting state Time resolution of computed tomography CT equipment depends on the rotation speed of the Xray tube and detector Since the rotation speed is eventually limited images are likely to be affected by heart beats in patients with a high heart rate 12 In order to reduce the time resolution by half dual source CT equipment with two tubes and two detectors has been developed 13 However it has not proved popular because its use is limited to heart imaging only Current CCTA guidelines published by the Society of Cardiovascular Computed Tomography recommend the use of βblockers to prevent motion artifacts due to heart beats 14 15 16 17 18 19 However metoprolol a commonly prescribed highly β1selective drug achieves its maximum βblocking effect at 1–2 h after administration with a duration of at least 6–8 h 20 21Landiolol hydrochloride −S22dimethyl13dioxolan4yl methyl 34S2hydroxy32morpholinocarbonylaminoethylamino propoxy phenylpropionate monohydrochloride is a β1blocker developed by Ono Pharmaceutical Co Ltd Osaka Japan in 1991 Having an ester bond it has a short plasma halflife during which it is metabolized and inactivated by esterases in the blood and liver Furthermore landiolol hydrochloride has high selectivity for β1 receptors with a β1/β2 ratio of approximately 250 22 23The optimal dose of βblockers varies according to race 24 25 Since landiolol hydrochloride has a rapid onset and short βblocking effect we considered that this drug would be effective for controlling heart rate during CCTA On this basis we determined the optimal dose of landiolol hydrochloride in Japanese subjects with suspected ischemic heart disease undergoing CCTA in an openlabel comparative study

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