Cimetidine sulfoxide
(Synonyms: 西咪替丁亚砜; Cimetidine sulphoxide) 目录号 : GC62267
Cimetidine sulfoxide (Cimetidine sulphoxide) 是一种 Cimetidine 的亚砜代谢产物。Cimetidine 是一种组胺 H2 受体 (H2-receptor) 拮抗剂，可用于消化性溃疡和上消化道出血的研究。
Cas No.:54237-72-8
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
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- Purity: >99.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Cimetidine sulfoxide (Cimetidine sulphoxide) is a sulfoxide metabolite of Cimetidine. Cimetidine is a histamine H2-receptor antagonist. Cimetidine has the potential for peptic ulcer disease and upper gastrointestinal haemorrhage treatment[1].
Active transport of Cimetidine across the rat small intestine is observable at lower substrate concentrations (40 and 200 μM), but is masked by passive transfer at higher concentrations (400 μM). Cimetidine sulfoxide is detected after some incubations[2].
The enantiomeric composition of Cimetidine sulfoxide is also determined in rat urine (24 h) following the administration of Cimetidine (30 mg/kg; po) to male Wistar rats. The enantiomeric ratio in this case is found to be (+/-) 57:43[3].
[1]. Larsson R, et al. The pharmacokinetics of cimetidine and its sulphoxide metabolite in patients with normal and impaired renal function. Br J Clin Pharmacol. 1982;13(2):163-170.
[2]. HE Barber, et al. The Transport of Cimetidine Across the Rat Small Intestine in Vitro. B r J Pharmacol. 1979 Jul;66(3):496P-497P.
[3]. Ryta A. Kuzel, et al. Investigations into the chirality of the metabolic sulfoxidation of cimetidine. Chirality (1994), 6(8), 607-14.
| Cas No. | 54237-72-8 | SDF | |
| 别名 | 西咪替丁亚砜; Cimetidine sulphoxide | ||
| 分子式 | C10H16N6OS | 分子量 | 268.34 |
| 溶解度 | DMSO : 83.33 mg/mL (310.54 mM; ultrasonic and warming and heat to 60°C) | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 3.7266 mL | 18.6331 mL | 37.2662 mL |
| 5 mM | 0.7453 mL | 3.7266 mL | 7.4532 mL |
| 10 mM | 0.3727 mL | 1.8633 mL | 3.7266 mL |
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| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
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| % DMSO % % Tween 80 % saline | ||||||||||
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工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
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Quantitation of cimetidine and Cimetidine sulfoxide in serum by solid-phase extraction and solvent-recycled liquid chromatography
J Anal Toxicol 1985 Jul-Aug;9(4):161-6.PMID:4033072DOI:10.1093/jat/9.4.161.
A high performance liquid chromatographic method for the simultaneous determination of cimetidine and its major metabolite, Cimetidine sulfoxide, was developed. These compounds and the internal standard, ornidazole, were extracted from 0.5 mL of serum using a solid phase Bond Elut C18 analytical column with detection at 229 nm. Absolute recoveries were 94 to 103%, 93 to 104%, and 95 to 105% for cimetidine, Cimetidine sulfoxide, and ornidazole, respectively. The minimum detection limit for cimetidine was 0.1 mg/L and for Cimetidine sulfoxide was 0.05 mg/L when the concentrating step was used. Cimetidine and Cimetidine sulfoxide demonstrated linearity up to 10 mg/L and 7.5 mg/L respectively, with the between-run precision of less than a 5% coefficient of variation for both compounds. Interferences from other drugs tested or endogenous substances in serum were not detected. The mobile phase was recycled to maintain better long term column stability and to minimize solvent cost. The instability of the drugs in solution was circumvented with a reduced-pressure drying process that produced working standards possessing longterm stability. The problem of drug interconversion observed during sample storage and with concentrating steps was controlled also. In addition, a resolution test mixture was chromatographed daily to control chromatographic quality.
Cimetidine clearance in the obese
Clin Pharmacol Ther 1985 Apr;37(4):425-30.PMID:3979004DOI:10.1038/clpt.1985.66.
Six subjects with normal weight (mean weight = 62 kg) and six obese subjects (mean weight = 140 kg) were given a single intravenous cimetidine infusion of 600 mg over 10 to 15 minutes. Both groups of subjects had normal serum creatinine levels and were matched with respect to age, desirable body weight, height, renal function, and sex. Compared with subjects of normal weight, obese subjects had higher cimetidine systemic (1147 and 637 ml/min) and renal (808 and 318 ml/min) clearances. Volume of distribution at steady state was of the same order for the two groups (82 and 84 L), but the t 1/2 was shorter in the obese group (1.2 and 1.9 hr). Obese subjects had lower Cimetidine sulfoxide serum concentrations and greater Cimetidine sulfoxide renal clearance (856 and 509 ml/min). Cimetidine systemic clearance and Cimetidine sulfoxide renal clearance values were of the same order in the two groups when normalized by the value of weight raised to the 0.76 and 0.5 powers. Under the assumptions of an average weight of 70 kg and that average serum concentrations produced by cimetidine, 300 mg iv every 6 hours, are appropriate, people with normal renal function and body weight usually receive 48 mg/day/weight0.76. This same dosage in obese individuals with normal serum creatinine values should result in the same average steady-state serum concentrations. In our obese subjects, the mean cimetidine dose would have been approximately 500 mg iv every 6 hours.
Cimetidine secretion by rabbit renal tubules in vitro
Am J Physiol 1981 Jul;241(1):F69-76.PMID:7246776DOI:10.1152/ajprenal.1981.241.1.F69.
Cimetidine, a drug in widespread use in the treatment of peptic ulcer disease, is eliminated primarily via urinary excretion. We examined cimetidine transport by rabbit proximal straight tubules perfused in vitro. [3H]Cimetidine in the bath was actively secreted into the tubule lumen. There was a curvilinear relationship between the rate of cimetidine secretion and the concentration of bath cimetidine. Cimetidine secretion was inhibited by hypothermia and ouabain. Quinine, tolazoline, probenecid, phloridzin, creatinine, p-aminohippurate, and Cimetidine sulfoxide inhibited cimetidine secretion in a dose-related manner. At low cimetidine concentrations lumen-to-bath transport rates were only 11-18% of bath-to-lumen secretory rates. High performance liquid chromatographic analysis of collected tubular fluid showed a predominance of cimetidine and a small amount of Cimetidine sulfoxide in ratios similar to those of the bath. These studies show that cimetidine is actively secreted into the lumen of rabbit proximal straight tubules in vitro. Secretion probably occurs via the organic base and to a lesser extent the acid transport systems.
Intestinal clearance of H2-antagonists
Biochem Pharmacol 1994 Jul 19;48(2):229-31.PMID:7914403DOI:10.1016/0006-2952(94)90091-4.
Jejunal perfusion of cimetidine resulted in the appearance of lumenal Cimetidine sulfoxide in both rats and humans. In the rat, ileal perfusion yielded negligible sulfoxide metabolite as compared with that of the jejunum. Jejunal co-perfusion of an anionic-exchange inhibitor, 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid, blocked the appearance of drug sulfoxide, and methionine co-perfusion yielded concentration-dependent inhibition of lumenal Cimetidine sulfoxide. Intravenous injection of high concentrations of Cimetidine sulfoxide did not produce detectable lumenal metabolite levels during jejunal perfusion of drug-free buffer, providing in situ evidence that lumenal metabolite is generated by the small intestine. The extent of the appearance of lumenal sulfoxide was significantly greater for cimetidine than for the other three marketed H2-antagonists in rat jejunum. Variable intestinal clearance of this extensively prescribed class of therapeutic agents may contribute to their absorption variability.
Cimetidine absorption and elimination in rat small intestine
Drug Metab Dispos 2000 Jan;28(1):65-72.PMID:10611142doi
The purpose of this study was to determine the characteristics of intestinal absorption and metabolism of cimetidine. The initial finding of the appearance of Cimetidine sulfoxide in rat and human jejunum from cimetidine perfusions had prompted an isolation of mucosal membrane transport and enterocyte metabolism contributions in earlier membrane vesicle and microsomal studies, respectively. In this report, perfusion studies in rat small intestine detail regional differences in intestinal elimination. Cimetidine S-oxide appears to a significantly greater extent in the jejunum compared with the ileum. Jejunal metabolite appearance is shown to be a function of the pH-dependent intracellular uptake of cimetidine. Cimetidine permeability decreases with increasing perfusion concentration in both jejunum and ileum. Similar permeability magnitudes and concentration dependence are observed in both regions. Perfusion studies with inhibitors of cimetidine mucosal transport and inhibitors of microsomal S-oxidation provide an inhibition profile suggesting that jejunal cimetidine permeability decreases with increasing intracellular cimetidine concentration. The data support a reduction in paracellular cimetidine absorption as controlled by intracellular cimetidine. This inference is drawn on the basis of mass balance. Because significant appearance of cimetidine S-oxide was previously found in human jejunal perfusions, this region-dependent intestinal elimination process detailed in rats may be relevant to drug plasma-level double peaks observed in clinical studies. Saturation of jejunal metabolism at typical oral doses may limit paracellular absorption of cimetidine in the jejunum and contribute to the double peak phenomenon and to absorption variability.