阿司匹林动物与人给药量对比

一般来说,正常服药治疗后血浆中水杨酸含量为30-100毫克每升,高剂量服用的患者血浆中的含量为50-300毫克每升,急性中毒患者血浆中的含量为700-1400毫克每升。服用次水杨酸铋、水杨酸甲酯和水杨酸钠后也会产生水杨酸。

Morra P, Bartle WR, Walker SE, Lee SN, Bowles SK, Reeves RA. Serum concentrations of salicylic acid following topically applied salicylate derivatives. Ann. Pharmacother. 1996, 30 (9): 935–40. PMID 8876850.
 R. Baselt. Disposition of Toxic Drugs and Chemicals in Man 9th. Seal Beach, California: Biomedical Publications. 2011: 20–23.

水杨酸主要通过肾脏作为水杨酰胺乙酸(75%)、游离水杨酸(10%)、水杨酸苯酚(10%)、酰基葡萄糖醛酸苷(5%)、龙胆酸(< 1%)、2,3-二羟基苯甲酸排泄。
2,3-Dihydroxybenzoic acid is a product of human aspirin metabolism. Martin Grootveld and Barry Halliwell, Biochemical Pharmacology, Volume 37, Issue 2, 15 January 1988, pages 271–280, doi:10.1016/0006-2952(88)90729-0

当摄入低剂量时(小于250mg,成人),所有途径都通过一级动力学,消除半衰期约为2.0至4.5小时。

Hartwig, Otto H. Pharmacokinetic considerations of common analgesics and antipyretics. American Journal of Medicine. 1983-11-14, 75 (5A): 30–7. PMID 6606362. doi:10.1016/0002-9343(83)90230-9.
Done, AK. Salicylate intoxication. Significance of measurements of salicylate in blood in cases of acute ingestion. Pediatrics. November 1960, 26: 800–7. PMID 13723722.

当摄入高剂量水杨酸时(大于4000mg),半衰期会延长至15-30小时,

Chyka PA, Erdman AR, Christianson G, Wax PM, Booze LL, Manoguerra AS, Caravati EM, Nelson LS, Olson KR, Cobaugh DJ, Scharman EJ, Woolf AD, Troutman WG; Americal Association of Poison Control Centers; Healthcare Systems Bureau, Health Resources and Services Administration, Department of Health and Human Services. Salicylate poisoning: an evidence-based consensus guideline for out-of-hospital management. Clin Toxicol (Phila). 2007, 45 (2): 95–131. PMID 17364628. doi:10.1080/15563650600907140.

因为水杨酰胺乙酸和水杨酚醛葡糖苷酸的生物转化途径已饱和。

Prescott LF, Balali-Mood M, Critchley JA, Johnstone AF, Proudfoot AT; Balali-Mood; Critchley; Johnstone; Proudfoot. Diuresis or urinary alkalinisation for salicylate poisoning?. Br Med J (Clin Res Ed). 1982, 285 (6352): 1383–6. PMC 1500395. PMID 6291695. doi:10.1136/bmj.285.6352.1383.

代谢途径的饱和使得肾脏对水杨酸的排泄更加重要,而尿液酸碱度对其影响也更为敏感。当尿液的pH值从5升至8时,肾脏对水杨酸的清除能力会提升10-20倍。通过碱化尿液来增加水杨酸的清除率便是利用了这一点。

Dargan PI, Wallace CI, Jones AL.; Wallace; Jones. An evidenced based flowchart to guide the management of acute salicylate (aspirin) overdose. Emerg Med J. 2002, 19 (3): 206–9. PMC 1725844. PMID 11971828. doi:10.1136/emj.19.3.206.

止痛用的阿司匹林,规格是325毫克(5格令)

一般来说,成人用于治疗发烧或关节炎时每天服用四次,

英国国家处方集 45. British Medical Journal and 英国皇家药师协会. 2003.

这和以前治疗风湿热时所用的剂量接近。

Aspirin monograph: dosages, etc. Medscape.com. [2011-05-11].

有或怀疑有冠状动脉病史的人要预防心肌梗塞(MI),每天低剂量服用一次即可。

参考中国实验动物中心的给药剂量
小鼠给药量 25mg/kg x 0.02kg==0.5mg,0.5mg x 388=194mg 人的给药量,浓度194/70=2.77mg/kg。

文献A comprehensive in vivo and mathematic modeling-based kinetic characterization for aspirin-induced chemoprevention in colorectal cancer下载链接原文链接给药方法和剂量:研究人员将432只小鼠分为四组:对照组,低剂量阿司匹林(15mg/ kg),中剂量阿司匹林(50mg/ kg)和高剂量阿司匹林(100mg/ kg)-小鼠。当量人类100mg,300mg和600毫克。

文献Therapeutic utility of aspirin in the ApcMin/+ murine model of colon carcinogenesis给药方法和剂量25mg/kg

Treatment protocol
Min/+ mice were treated for a period of 28 days either with vehicle or aspirin (25 mg/kg/day). Dose of aspirin correlates to previous work conducted by Mahmoud et al. [9], which demonstrated that 0.5 mg of aspirin per day was chemopreventive in Min/+ mice. Aspirin was initially dissolved in dimethyl sulfoxide (DMSO; 5% by final volume) and then diluted to the desired concentration (5 mg/mL) with 0.5% carboxymethylcellulose (CMC). Both aspirin and drug vehicle were orally administered via a 22-gauge feeding needle (Kent Scientific Co., Litchfield, CT) attached to a 1 cc syringe. Compounds were delivered at a rate of 5 mL/kg body weight. A diluted concentration was used to aid in drug solubility and accuracy of drug administration.

文献Low dose aspirin blocks breast cancer-induced cognitive impairment in mice给药方法和剂量25mg/kg

Anti-inflammatory treatment
BALB/c mice were treated with either asprin in drinking water (Aspro, Bayer Australia Ltd) (0.125 μg/ml) or water (control) beginning 36 h prior to tumor cell injection and continuing throughout the experiment. Water was changed every 12 h and liquid consumption quantified. Mice were pre-determined to drink an average of 4 ml/day resulting in an estimated dose of 25 mg/kg/day. This dose has been shown to produce a similar pharmacodynamic effect on COX-1 inhibition as a dose of 100 mg/day in humans, which is considered a low dose [35].

文献Effect of Different Doses of Acetylsalicylic Acid on the Antithrombotic Activity of Clopidogrel in a Mouse Arterial Thrombosis Model给药方法和剂量5mg/kg

Oral Delivery of ASA and Clopidogrel
Age-matched C57BL/6J male mice (000664; Jackson Laboratories) weighing at least 25 g were used at 8 to 12 weeks of age. Anesthesia was initiated with an intraperitoneal injection of 125 mg/kg of ketamine (02173239; Wyeth Animal Health), 12.5 mg/kg of xylazine (02169592; Bayer), and 0.25 mg/kg of atropine (00238481; Rafter 8) and maintained with Nembutal (86665/04; Ceva Sante Animal). All mice received 100 μL of vehicle or an equal volume of ASA, clopidogrel or both by gavage using 20-gauge animal feeding needles (7910; Popper and Sons, Inc). ASA was given only once, 4 hours before study, whereas clopidogrel was given twice: 24 and 4 hours before study. ASA and clopidogrel were given at doses up to 5 mg/kg body weight.

文献Time-Dependent Hypotensive Effect of Aspirin in Mice给药方法和剂量50 μg/d in 100 μL of water

Experimental Design for BP Recording
Twelve-week-old male C57BL/6 mice acclimatized to a 12/12-hour light/dark cycle for 1 week before radiotelemetry implantation. Although our studies were confined to male mice, the clinical reports of time-dependent hypotensive effects of low-dose aspirin are evident in both genders. The basal BP and heart rate (HR) recordings began 7 days after this operation. Mice were subjected to a high-salt diet (HSD, 8% NaCl) for 2 weeks to evoke a hypertensive response, better to clarify the phenotype, then divided randomly into 2 groups and treated with aspirin (50 μg/d in 100 μL of water) by gavage at zeitgeber time (ZT) 0 or ZT12 for 7 consecutive days followed by BP recording. Urine was collected for 24 hours using metabolic cages after each BP recording. At the end of the experiment, mice were euthanized by CO2 inhalation for tissue sample collections (Figure 1). Samples were stored at −80°C until use.