Clotiazepam has been trialed and found to be effective in the short-term management ofanxiety.[9] Clotiazepam is also used as apremedicant in minor surgery inFrance andJapan, where the drug is commercially available under the brand namesVeratran andRize, respectively.[10][11]
A cross-over study in six healthy volunteers (median age 28 years) was conducted using single-dose pharmacokinetics of 5 mg clotiazepamdrops,oral tablets, andsublingual tablets. The formulations had similar systemic availability. Compared with oral tablets, the sublingual route gave a lower peak concentration and a delayed peak time, while drops gave a greater maximum concentration with a similar peak time. The use of drops is suggested for a more marked initial effect and the sublingual route for easier administration, especially in the elderly.[12]
Similar to other benzodiazepines clotiazepam hasanxiolytic,sedative,hypnotic,amnesic,anticonvulsant andmuscle relaxant pharmacological properties.[7] Clotiazepam binds to the benzodiazepine site of the GABAA receptor where it acts as a full agonist; this action results in an enhanced GABA inhibitory effect at the GABAA receptor which results in the pharmacological effects of clotiazepam.[13]
Clotiazepam has a shortelimination half-life and is less prone to accumulation after repeated dosing compared to longer-acting benzodiazepine agents. It is metabolised via oxidation.[14] Clotiazepam is metabolised to hydroxy-clotiazepam and desmethyl-clotiazepam. After oral ingestion of a single 5 mg dose of clotiazepam by three healthy volunteers the drug was rapidly absorbed.[15] The elimination half-life of the drug and its metabolites range from 6.5 hours to 18 hours. Clotiazepam is 99 percent bound to plasma protein.[15] In elderly men the elimination half-life is longer and in elderly women the volume of distribution is increased.[16] Individuals with liver impairment have a reduced volume of distribution as well as a reduced total clearance of clotiazepam; renal impairment does not affect the kinetics of clotiazepam.[17]
The dose equivalent to 10 mg diazepam is thought to be between 5 and 10 mg clotiazepam.
Side effects experienced with this product will resemble those of other benzodiazepines.Drowsiness andasthenia are common side effects.[18] There has been a report of reversiblehepatitis caused by clotiazepam.[19]
^"Clotiazépam"(PDF).HAS - Direction de l'Evaluation Médicale. Economique et de Santé Publique. 20 May 2015.
^DE 2107356, Nakanishi M, Kazuhiko A, Tetsuya T, Shiroki M, "Thieno-(2,3-E)(1,4)diazepin-2-ones", issued 3 May 1978, assigned to Yoshitomi Pharmaceutical Industries, Ltd.
^Klicpera C, Strian F (May 1978). "Autonomic perception and responses in anxiety-inducing situations".Pharmakopsychiatrie, Neuro-Psychopharmakologie.11 (3):113–120.doi:10.1055/s-0028-1094569.PMID27828.
^Nakazawa Y, Kotorii M, Oshima M, Horikawa S, Tachibana H (October 1975). "Effects of thienodiazepine derivatives on human sleep as compared to those of benzodiazepine derivatives".Psychopharmacologia.44 (2):165–171.doi:10.1007/BF00421005.PMID709.S2CID13365554.
^Martucci N, Manna V, Agnoli A (April 1987). "A clinical and neurophysiological evaluation of clotiazepam, a new thienodiazepine derivative".International Clinical Psychopharmacology.2 (2):121–128.doi:10.1097/00004850-198704000-00005.PMID2885366.
^"RIZE TABLETS 5mg".Official Japanese Drug Information Sheet (Kusuri-no-Shiori). February 2016.
^Benvenuti C, Bottà V, Broggini M, Gambaro V, Lodi F, Valenti M (1989). "The pharmacokinetics of clotiazepam after oral and sublingual administration to volunteers".European Journal of Clinical Pharmacology.37 (6):617–619.doi:10.1007/BF00562556.PMID2575522.S2CID29397932.
^abArendt R, Ochs HR, Greenblatt DJ (1982). "Electron capture GLC analysis of the thienodiazepine clotiazepam. Preliminary pharmacokinetic studies".Arzneimittel-Forschung.32 (4):453–455.PMID6125154.
^Ochs HR, Greenblatt DJ, Verburg-Ochs B, Harmatz JS, Grehl H (1984). "Disposition of clotiazepam: influence of age, sex, oral contraceptives, cimetidine, isoniazid and ethanol".European Journal of Clinical Pharmacology.26 (1):55–59.doi:10.1007/BF00546709.PMID6143670.S2CID44321356.
^Ochs HR, Greenblatt DJ, Knüchel M (1986). "Effect of cirrhosis and renal failure on the kinetics of clotiazepam".European Journal of Clinical Pharmacology.30 (1):89–92.doi:10.1007/BF00614202.PMID2872061.S2CID21304989.
^Colonna L, Cozzi F, Del Citerna F, Di Benedetto A, De Divitiis O, Furlanello F, et al. (1990). "[Multicenter study of the effectiveness and tolerance of clotiazepam in cardiology]".Minerva Cardioangiologica.38 (1–2):45–49.PMID1971433.
^Shimamine M, Masunari T, Nakahara Y (1993). "[Studies on identification of drugs of abuse by diode array detection. I. Screening-test and identification of benzodiazepines by HPLC-DAD with ICOS software system]".Eisei Shikenjo Hokoku. Bulletin of National Institute of Hygienic Sciences (111):47–56.PMID7920567.
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