Jansson R, Dahlberg P A, Lindström B
Int J Clin Pharmacol Ther Toxicol. 1983 Oct;21(10):505-10.
In this study we investigated the oral bioavailability of therapeutic doses of two antithyroid drugs, methimazole and carbimazole, in seven euthyroid subjects. To increase the statistical power deuterium-labeled methimazole was given orally as an internal standard together with the tested drugs. Using a recently described highly sensitive gas chromatographic-mass spectrometric assay for methimazole we found that intake of 15 mg carbimazole resulted in plasma concentrations of methimazole and pharmacokinetic data comparable to intake of an equimolar amount of methimazole, i. e., 9.2 mg. Maximum concentrations of 163 and 149 ng/ml, respectively, were reached in both instances at 0.9 h after intake of 15 mg carbimazole and 10 mg methimazole. The plasma half-life was 5.7 and 5.4 h, respectively. In contrast to previous suggestions the interindividual differences in pharmacokinetics were small. In conclusion, carbimazole was rapidly and totally bioactivated to methimazole, and the drugs should be regarded as equipotent when compared on a molar basis.
在本研究中,我们调查了7名甲状腺功能正常的受试者口服治疗剂量的两种抗甲状腺药物甲巯咪唑和卡比马唑后的口服生物利用度。为了提高统计效能,将氘标记的甲巯咪唑作为内标与受试药物一起口服。使用最近描述的一种针对甲巯咪唑的高灵敏度气相色谱 - 质谱分析法,我们发现摄入15 mg卡比马唑后,甲巯咪唑的血浆浓度和药代动力学数据与摄入等摩尔量的甲巯咪唑(即9.2 mg)相当。在摄入15 mg卡比马唑和10 mg甲巯咪唑后,分别在0.9小时达到最大浓度163和149 ng/ml。血浆半衰期分别为5.7小时和5.4小时。与之前的观点相反,药代动力学的个体间差异很小。总之,卡比马唑迅速且完全生物活化成甲巯咪唑,在摩尔基础上比较时,这两种药物应被视为等效。