Influence of Hepatic Impairment on??the Pharmacokinetics and Pharmacodynamics of Landiolol??Hydrochloride, an Ultra-Short-Acting ??1-Blocker

Takahata, Takenori; Yasui‐Furukori, Norio; Sakamoto, Juichi; Suto, Koji; Suto, T; Tateishi, Tetsuya; Munakata, Akihiro

doi:10.2165/00126839-200506060-00006

Cited by 17 publications

(13 citation statements)

References 9 publications

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“…Moreover, since the PK values obtained in the present study improved the precision with which plasma concentration of landiolol could be predicted, the accuracy of TCI was expected to increase after the modification of the PK parameters that are influenced by gender, age, and concomitant use of drugs, including anesthetics. These effects, however, were limited because landiolol is predominantly metabolized by the pseudocholinesterase, which is abundant in plasma [15]. Since the concentration of landiolol is subject to change as a result of the continuous infusion dose because of its rapid action and ease of titration, the merit of TCI is not as large as it is for long-acting anesthetics.…”

Section: Discussionmentioning

confidence: 99%

Target-controlled infusion and population pharmacokinetics of landiolol hydrochloride in gynecologic patients

et al. 2014

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Section: Discussionmentioning

confidence: 99%

Target-controlled infusion and population pharmacokinetics of landiolol hydrochloride in gynecologic patients

et al. 2014

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“…The lower limits of quantification were 0.05 mg/ml for landiolol and 0.1 mg/ml for M-1. These methods were successfully applied to a pharmacokinetic study in humans 5,6) and the characterization of blood pharmacokinetics of landiolol and M-1 at a therapeutic dosage. We think that these methods contribute to progress of clinical research of landiolol hydrochloride.…”

Section: Discussionmentioning

confidence: 99%

“…About the quantitation method of landiolol and its major metabolite, although the summarized method was already reported, 5,6) the method details and validation data had not been reported.…”

mentioning

confidence: 99%

Validation of HPLC-UV Methods for Quantitatively Determining Landiolol and Its Major Metabolite in Human Blood

Hashimoto

Nago

Tsunekawa

et al. 2009

Biological & Pharmaceutical Bulletin

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Landiolol hydrochloride is a newly developed cardioselective, ultra short-acting b 1 -adrenergic receptor blocking agent. Landiolol hydrochloride has much higher cardioselectivity (b 1 /b 2 ϭ255) than currently available b 1 -blockers, such as esmolol hydrochloride (b 1 /b 2 ϭ33).1) This drug is rapidly hydrolyzed by both carboxylesterase in the liver and pseudocholinesterase in the plasma 2) to an inactive metabolite (M-1) with a rapid elimination half-life of about 4 min, which is significantly shorter than the elimination half-lives of conventional b 1 -blockers.3) Based on these features, landiolol hydrochloride has been used in the emergency management of atrial fibrillation, atrial flutter and tachycardia as well as in perioperative arrhythmia control.The introduction of a target controlled infusion (TCI) system into clinical practice ensures that a target plasma drug concentration is obtained to induce and maintain anesthesia during perioperative anesthetic management. Based on a pharmacokinetic model, the TCI system determines the initial loading dose needed to achieve a target plasma drug concentration and the infusion rate needed to maintain a constant concentration, and controls the intravenous infusion completely automatically.4) Therefore, application of the TCI system to landiolol hydrochloride administration is expected to allow more effective and safe drug administration.After the quantitation of landiolol in blood, establishing the pharmacokinetic model is necessary for the application of the TCI system. About the quantitation method of landiolol and its major metabolite, although the summarized method was already reported, 5,6) the method details and validation data had not been reported.In this report, validated HPLC-UV methods that quantitatively determine landiolol and its major metabolite in human blood were reported in order to contribute to progress of clinical research of landiolol hydrochloride such as the application of the TCI system. MATERIALS AND METHODS Chemical and ReagentsLandiolol, M-1, an internal standard for landiolol (IS-1), and an internal standard for M-1 (IS-2) were synthesized at Ono Pharmaceutical Co., Ltd. Methanol, ethanol, acetonitrile, ethyl acetate were HPLC January 2009 121 Notes Validation of HPLC-UV Methods for Quantitatively Determining Landiolol and Its Major Metabolite in Human BloodYoshitaka HASHIMOTO,* Sachiko NAGO, Masako TSUNEKAWA, Kimio SHIBAKAWA, and Yasuyuki MIYATA Pharmacokinetic Research Laboratories, Research Headquarters, Ono Pharmaceutical Co., Ltd.; 17-2 Wadai, Tsukubashi, Ibaraki 300-4247, Japan. Received June 24, 2008; accepted October 15, 2008; published online October 16, 2008 Landiolol is an ultra-short-acting b b 1 -adrenergic receptor blocking agent that is used for both perioperative and postoperative patients with tachycardia during general anesthesia. Validated HPLC-UV methods that quantitatively determine landiolol and its major metabolite (M-1) in human blood were reported for clinical research of landiolol. These analytes were...

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“…Due to the presence of an ester group, landiolol is hydrolyzed very quickly by both pseudocholinesterase in plasma and carboxylesterase in the liver such that the elimination half-life (t 1/2 of 4 min) is significantly shorter than that of conventional ␤ 1 -receptor antagonists [8][9][10][11]. These characteristics make landiolol a promising alternative to esmolol.…”

Section: Introductionmentioning

confidence: 99%

Determination of landiolol, an ultra-short-acting β1-receptor antagonist, in human plasma by liquid chromatography–tandem mass spectrometry

Shi

Liu

et al. 2012

Journal of Chromatography B

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Influence of Hepatic Impairment on??the Pharmacokinetics and Pharmacodynamics of Landiolol??Hydrochloride, an Ultra-Short-Acting ??1-Blocker

Cited by 17 publications

References 9 publications

Target-controlled infusion and population pharmacokinetics of landiolol hydrochloride in gynecologic patients

Target-controlled infusion and population pharmacokinetics of landiolol hydrochloride in gynecologic patients

Validation of HPLC-UV Methods for Quantitatively Determining Landiolol and Its Major Metabolite in Human Blood

Determination of landiolol, an ultra-short-acting β1-receptor antagonist, in human plasma by liquid chromatography–tandem mass spectrometry

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