药物化合物包括碳、氢和其他元素的稳定重同位素，在药物开发过程中主要作为定量示踪剂。由于氘化可能会影响药物的药代动力学和代谢特性，因此值得关注[1]。

Absorption, Distribution and Excretion
**Oral**: Following oral administration, capsaicin may be absorbed by a nonactive process from the stomach and whole intestine with an extent of absorption ranging between 50 and 90%, depending on the animal. The peak blood concentration can be reached within 1 hour following administration. Capsaicin may undergo minor metabolism in the small intestine epithelial cells post-absorption from the stomach into the small intestines. While oral pharmacokinetics information in humans is limited, ingestion of equipotent dose of 26.6 mg of pure capsaicin, capsaicin was detected in the plasma after 10 minutes and the peak plasma concentration of 2.47 ± 0.13 ng/ml was reached at 47.1 ± 2.0 minutes. **Systemic**: Following intravenous or subcutaneous administration in animals, the concentrations in the brain and spinal cord were approximately 5-fold higher than that in blood and the concentration in the liver was approximately 3-fold higher than that in blood. **Topical**: Topical capsaicin in humans is rapidly and well absorbed through the skin, however systemic absorption following topical or transdermal administration is unlikely. For patients receiving the topical patch containing 179 mg of capsaicin, a population analysis was performed and plasma concentrations of capsaicin were fitted using a one-compartment model with first-order absorption and linear elimination. The mean peak plasma concentration was 1.86 ng/mL but the maximum value observed in any patient was 17.8 ng/mL.
It is proposed that capsaicin mainly undergoes renal excretion, as both the unchanged and glucuronide form. A small fraction of unchanged compound is excreted in the feces and urine. _In vivo_ animal studies demonstrates that less than 10 % of an administered dose was found in faces after 48 h.
Prescription and nonprescription products for topical management of pain, including cream, lotion and patch forms, contain capsaicin (CAP) and dihydrocapsaicin (DHC). There are few in vivo studies on absorption, bioavailability, and disposition of CAP and DHC. We established a sensitive and rapid LC-MS/MS assay to determine CAP and DHC levels in rabbit plasma and tissue. Bio-samples prepared by liquid-liquid extraction using n-hexane-dichloromethane-isopropanol (100: 50: 5, v/v/v) mixture were separated by isocratic chromatography with an Extend C18 column. The mobile phase was acetonitrile-water-formic acid (70: 30: 0.1, v/v/v). The method was linear from 0.125 to 50 ng/mL for a 100 uL bio-sample, and the lower quantification limit was 0.125 ng/mL. Total run time to analyze each sample was 3.5 min. We used this validated method to study pharmacokinetics and tissue distribution of CAP gel administered topically to rabbits. A very small amount of CAP and DHC was absorbed into the systemic circulation. The highest plasma concentration was 2.39 ng/mL, and the mean peak plasma concentration value after 12 h of CAP gel application was 1.68 ng/mL. Drug concentration in treated skin was relatively high, with low concentration in other tissues. Thus, topical CAP gel had strong local effects and weaker systemic effects.

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Metabolism / Metabolites
Capsaicin metabolism after oral administration is unclear, however it is expected to undergo metabolism in the liver with minimal metabolism in the gut lumen. _In vitro_ studies with human hepatic microsomes and S9 fragments indicate that capsaicin is rapidly metabolized, producing three major metabolites, 16-hydroxycapsaicin, 17-hydroxycapsaicin, and 16,17-hydroxycapsaicin, whereas vanillin was a minor metabolite. It is proposed that cytochrome P450 (P450) enzymes may play some role in hepatic drug metabolism. _In vitro_ studies of capsaicin in human skin suggest slow biotransformation with most capsaicin remaining unchanged.
Capsaicin and dihydrocapsaicin are the major active components in pepper spray products, which are widely used for law enforcement and self-protection. The use of pepper sprays, due to their irreversible and other health effects has been under a strong debate. In this study, we compared metabolism and cytotoxicity of capsaicin and dihydrocapsaicin using human and pig liver cell fractions and human lung carcinoma cell line (A549) in vitro. Metabolites were screened and identified by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Using liver cell fractions, a novel aliphatic hydroxylated metabolite (m/z 322) was detected to dihydrocapsaicin but no structure was found corresponding to capsaicin. Instead, a novel phase I metabolite of capsaicin, corresponding to the structure of aliphatic demethylation and dehydrogenation (m/z 294) was identified. In addition, two novel conjugates, glycine conjugates (m/z 363 and m/z 365) and bi-glutathione (GSH) conjugates (m/z 902 and m/z 904), were identified for both capsaicin and dihydrocapsaicin. The medium of the exposed A549 cells contained omega-hydroxylated (m/z 322) and alkyl dehydrogenated (m/z 304) forms, as well as a glycine conjugate of capsaicin. As to dihydrocapsaicin, an alkyl dehydrogenated (m/z 306) form, a novel alkyl hydroxylated form, and a novel glycine conjugate were found. In A549 cells, dihydrocapsaicin evoked vacuolization and decreased cell viability more efficiently than capsaicin. Furthermore, both compounds induced p53 protein and G1 phase cell cycle arrest. Usefulness of the found metabolites as biomarkers for capsaicinoid exposures will need further investigations with additional toxicity endpoints.
... Dehydrogenation of capsaicin was a novel metabolic pathway and produced unique macrocyclic, diene, and imide metabolites. Metabolism of capsaicin by microsomes was inhibited by 1-aminobenzotriazole (1-ABT). Metabolism was catalyzed by CYP1A1, 1A2, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1, and 3A4. Addition of GSH (2 mM) to microsomal incubations stimulated the metabolism of capsaicin and trapped several reactive electrophilic intermediates as their GSH adducts. /Study conducted with recombinant P450 enzymes and hepatic and lung microsomes from various species, including humans/
The objectives of this study are to characterize capsaicin glucuronidation using liver microsomes and to determine the contribution of individual UDP-glucuronosyltransferase (UGT) enzymes to hepatic glucuronidation of capsaicin. The rates of glucuronidation were determined by incubating capsaicin with uridine diphosphoglucuronic acid-supplemented microsomes. Kinetic parameters were derived by model fitting. Determination of the relative activity factors, expression-activity correlation and activity correlation analysis were performed to identify the main UGT enzymes contributing to capsaicin metabolism. Capsaicin was efficiently glucuronidated in pooled human liver microsomes (pHLM). UGT1A1, 1A9 and 2B7 (as well as the gastrointestinal enzymes UGT1A7 and 1A8) showed considerable activities. Capsaicin glucuronidation was significantly correlated with 3-O-glucuronidation of beta-estradiol (r=0.637; p=0.014) and with UGT1A1 protein levels (r=0.616; p=0.019) in a bank of individual HLMs (n=14). Also, capsaicin glucuronidation was strongly correlated with zidovudine glucuronidation (r=0.765; p<0.01) and with UGT2B7 protein levels (r=0.721; p<0.01). UGT1A1, 1A9 and 2B7 contributed 30.3, 6.0 and 49.0% of total glucuronidation of capsaicin in pHLM, respectively. Further, glucuronidation of capsaicin by liver microsomes showed marked species difference.

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Biological Half-Life
Following oral ingestion of equipotent dose of 26.6 mg of pure capsaicin, the half life was approximately 24.9 ± 5.0 min. Following topical application of 3% solution of capsaicin, the half-life of capsaicin was approximately 24 h. The mean population elimination half-life was 1.64 h following application of a topical patch containing 179 mg of capsaicin.

Effects During Pregnancy and Lactation
◉ Summary of Use during Lactation
No information is available on the clinical use of topical capsaicin during breastfeeding. However, capsaicin is poorly absorbed after topical application, so it is not likely to reach the bloodstream of the infant or cause any adverse effects in breastfed infants. Avoid application to the nipple area and ensure that the infant's skin does not come into direct contact with the areas of skin that have been treated.
◉ Effects in Breastfed Infants
Relevant published information was not found as of the revision date.
◉ Effects on Lactation and Breastmilk
Relevant published information was not found as of the revision date.
◈ What is capsaicin?
Capsaicin is the part of peppers (Solanaceae family, capsicum genus) that makes your mouth feel hot. Capsaicin has been generally recognized as safe (GRAS) by the U.S. Food and Drug Administration (FDA) for use in food and candy. It has been used in some cosmetics, and is the main ingredient in pepper spray used for defense.Capsaicin has been used to treat pain in topical (applied to the skin) preparations and has been given as an injection in the foot to help treat pain from Morton's neuroma (a nerve condition of the foot). Some brand names for topical preparations include Capazasin®, Qutenza®, and Zostrix®.Capsaicin has been sold in oral forms (such as pills and capsules) as an herbal supplement. The use of herbal products is generally not recommended during pregnancy unless under the direction and care of your healthcare provider to treat a medical condition. For more information about herbal products, please see our fact sheet at https://mothertobaby.org/fact-sheets/herbal-products-pregnancy/.
◈ I take capsaicin. Can it make it harder for me to get pregnant?
Studies have not been done in humans to see if using capsaicin would make it harder to get pregnant. Animal studies did not report that capsaicin affected female fertility.
◈ Does taking capsaicin increase the chance for miscarriage?
Miscarriage is common and can occur in any pregnancy for many different reasons. Studies have not been done to see if capsaicin increases the chance for miscarriage.
◈ Does taking capsaicin increase the chance of birth defects?
Every pregnancy starts out with a 3-5% chance of having a birth defect. This is called the background risk. Studies have not been done in humans to see if capsaicin increases the chance for birth defects above the background risk. Animal studies do not suggest that capsaicin would increase the chance for birth defects.
◈ Does taking capsaicin in pregnancy increase the chance of other pregnancy-related problems?
Studies have not been done in humans to see if capsaicin can cause other pregnancy-related problems, such as preterm delivery (birth before week 37) or low birth weight (weighing less than 5 pounds, 8 ounces [2500 grams] at birth).One animal study suggested that capsaicin might affect growth of the developing pregnancy.
◈ Does taking capsaicin in pregnancy affect future behavior or learning for the child?
Studies have not been done to see if capsaicin can cause behavior or learning issues for the child.
◈ Breastfeeding while taking capsaicin:
Capsaicin has not been studied for use while breastfeeding. There is a report of two breastfed infants who developed skin rashes when they nursed 12 and 15 hours after the person who was breastfeeding ate foods that were flavored with red pepper. The skin reactions in the nursing infants slowly went away over a period of several days. If you suspect the baby has any symptoms, such as a rash, contact the child’s healthcare provider. Be sure to talk to your healthcare provider about all of your breastfeeding questions.
◈ If a male takes capsaicin, could it affect fertility (ability to get partner pregnant) or increase the chance of birth defects?
Studies have not been done in humans to see if capsaicin could affect male fertility or increase the chance of birth defects above the background risk. Animal studies have not suggested that capsaicin could affect male fertility. In general, exposures that fathers or sperm donors have are unlikely to increase the risks to a pregnancy. For more information, please see the MotherToBaby fact sheet Paternal Exposures at https://mothertobaby.org/fact-sheets/paternal-exposures-pregnancy/.

[1]. Impact of Deuterium Substitution on the Pharmacokinetics of Pharmaceuticals. Ann Pharmacother. 2019;53(2):211-216.

[2]. Effects of piperine, the pungent component of black pepper, at the human vanilloid receptor (TRPV1). Br J Pharmacol. 2005 Mar;144(6):781-90.

[3]. The Effect of Capsaicin on Salivary Gland Dysfunction. Molecules. 2016 Jun 25;21(7).

[4]. Capsaicin provokes apoptosis and restricts benzo(a)pyrene induced lung tumorigenesis in Swiss albino mice. Int Immunopharmacol. 2013 Jun 6;17(2):254-259.

Capsaicin is a capsaicinoid. It has a role as a non-narcotic analgesic, a voltage-gated sodium channel blocker and a TRPV1 agonist.
Capsaicin is most often used as a topical analgesic and exists in many formulations of cream, liquid, and patch preparations of various strengths; however, it may also be found in some dietary supplements. Capsaicin is a naturally-occurring botanical irritant in chili peppers, synthetically derived for pharmaceutical formulations. The most recent capsaicin FDA approval was Qutenza, an 8% capsaicin patch dermal-delivery system, indicated for neuropathic pain associated with post-herpetic neuralgia.
Capsaicin has been reported in Capsicum pubescens, Capsicum annuum, and Capsicum with data available.
Capsaicin is a chili pepper extract with analgesic properties. Capsaicin is a neuropeptide releasing agent selective for primary sensory peripheral neurons. Used topically, capsaicin aids in controlling peripheral nerve pain. This agent has been used experimentally to manipulate substance P and other tachykinins. In addition, capsaicin may be useful in controlling chemotherapy- and radiotherapy-induced mucositis.
Capsaicin is identified as the primary pungent principle in Capsicum fruits. Hot chili peppers that belong to the plant genus Capsicum (family Solanaceae) are among the most heavily consumed spices throughout the world. The capsaicin content of green and red peppers ranges from 0.1 to 1%. Capsaicin evokes numerous biological effects and thus has been the target of extensive., investigations since its initial identification in 1919. One of the most recognized physiological properties of capsaicin is its selective effects on the peripheral part of the sensory nervous system, particularly on the primary afferent neurons. The compound is known to deplete the neurotransmitter of painful impulses known as substance P from the sensory nerve terminals, which provides a rationale for its use as a versatile experimental tool for studying pain mechanisms and also for pharmacotherapy to treat some peripheral painful states, such as rheumatoid arthritis, post-herpetic neuralgia, post-mastectomy pain syndrome and diabetic neuropathy. Considering the frequent consumption of capsaicin as a food additive and its current therapeutic application, correct assessment of any harmful effects of this compound is important from the public health standpoint. Ingestion of large amounts of capsaicin has been reported to cause histopathological and biochemical changes, including erosion of gastric mucosa and hepatic necrosis. However, there are contradictory data on the mutagenicity of capsaicin. A recent epidemiological study conducted in Mexico revealed that consumers of chili pepper were at higher risk for gastric cancer than non-consumers. However, it remains unclear whether capsaicin present in hot chili pepper is a major causative factor in the aetiology of gastric cancer in humans. A growing number of recent studies have focused on anticarcinogenic or antimutagenic phytochemicals, particularly those included in human diet. In summary, capsaicin has dual effects on chemically induced carcinogenesis and mutagenesis. Although a minute amount of capsaicin displays few or no deleterious effects, heavy ingestion of the compound has been associated with necrosis, ulceration and even carcinogenesis. Capsaicin is considered to be metabolized by cytochrome P-450-dependent mixed-function oxidases to reactive species. (A7835).
An alkylamide found in CAPSICUM that acts at TRPV CATION CHANNELS.
See also: Capsicum Oleoresin (active moiety of); Capsicum (part of); Paprika (part of) ... View More ...

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Drug Indication
The capsaicin 8% patch is indicated in the treatment of neuropathic pain associated with post-herpetic neuralgia. There are multiple topical capsaicin formulations available, including creams and solutions, indicated for temporary analgesia in muscle and join pain as well as neuropathic pain.
FDA Label
Qutenza is indicated for the treatment of peripheral neuropathic pain in adults either alone or in combination with other medicinal products for pain.

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Mechanism of Action
Capsaicin has been shown to reduce the amount of substance P associated with inflammation - however this is not believed to be its main mechanism in the relief of pain. Capsaicin's mechanism of action is attributed to "defunctionalization" of nociceptor fibers by inducing a topical hypersensitivity reaction on the skin. This alteration in pain mechanisms is due to many of the following: temporary loss of membrane potential, inability to transport neurotrophic factors leading to altered phenotype, and reversible retraction of epidermal and dermal nerve fiber terminals.
Capsaicin, the pungent constituent of chili peppers, represents the paradigm for the capsaicinoids or vanilloids, a family of compounds shown to stimulate and then desensitize specific subpopulations of sensory receptors, including C-polymodal nociceptors, A-delta mechanoheat nociceptors and warm receptors of the skin, as well as enteroceptors of thin afferent fibers. ...
... In rats desensitized by intraperitoneal (ip) capsaicin (i.e., abdominal non-systemic desensitization), mainly the first but not the later fever phases were reduced. The postprandial hyperthermia to intragastric injection of BaSO4 suspension was attenuated by either ip or perineural capsaicin treatment.
... Heat and protons as well as capsaicin activate VR1 to induce the influx of cations, particularly Ca2+ and Na+ ions. Characteristic effects of capsaicin are the induction of a burning sensation after acute administration and the desensitization of sensory neurons after large doses and prolonged administration. ... Capsaicin alters several visceral functions. ... Capsaicin affects thermoregulation after intra-hypothalamic injection and releases glutamate from the hypothalamus and cerebral cortex slices, while VR1-like immunoreactivity is not apparent in these regions.
... 0.4 and 4 uM of capsaicin produced a significant tonic block on voltage-activated Na+ current (I(Na)) evoked by a depolarizing step to -40 mV from a holding potential of -100 mV (49 +/- 7% n=11, p<0.05 and 72 +/- 13% n=4, p<0.05 respectively). ... Capsaicin slowed the time decay of inactivation of I(Na), and increased the time constant of the recovery of inactivation. Capsaicin and tetrodotoxin (TTX) depressed contractility of isolated electrically driven left rat atria, being the depression of maximal velocity of force development (dF/dt(max)) with respect to control values of 19 +/- 3% at 1 uM of capsaicin and 22 +/- 2% at 1 uM of TTX.
For more Mechanism of Action (Complete) data for CAPSAICIN (8 total), please visit the HSDB record page.

C18H27NO3

305.411885499954

305.199

1217899-52-9

Capsaicin;404-86-4

1548943

White to off-white solid powder

3.6

58.6

2

3

9

22

341

0

c1(OC)cc(CNC(=O)CCCC/C=C/C(C)C)ccc1O

YKPUWZUDDOIDPM-SOFGYWHQSA-N

InChI=1S/C18H27NO3/c1-14(2)8-6-4-5-7-9-18(21)19-13-15-10-11-16(20)17(12-15)22-3/h6,8,10-12,14,20H,4-5,7,9,13H2,1-3H3,(H,19,21)/b8-6+

(E)-N-[(4-hydroxy-3-methoxyphenyl)methyl]-8-methylnon-6-enamide

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

注意: 如下所列的是一些常用的体内动物实验溶解配方，主要用于溶解难溶或不溶于水的产品（水溶度<1 mg/mL）。 建议您先取少量样品进行尝试，如该配方可行，再根据实验需求增加样品量。

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注射用配方1: DMSO : Tween 80： Saline = 10 : 5 : 85 (如： 100 μL DMSO → 50 μL Tween 80 → 850 μL Saline)
*生理盐水/Saline的制备：将0.9g氯化钠/NaCl溶解在100 mL ddH ₂ O中，得到澄清溶液。
注射用配方 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (如： 100 μL DMSO → 400 μL PEG300 → 50 μL Tween 80 → 450 μL Saline)
注射用配方 3: DMSO : Corn oil = 10 : 90 (如： 100 μL DMSO → 900 μL Corn oil)
示例: 以注射用配方 3 (DMSO : Corn oil = 10 : 90) 为例说明, 如果要配制 1 mL 2.5 mg/mL的工作液, 您可以取 100 μL 25 mg/mL 澄清的 DMSO 储备液，加到 900 μL Corn oil/玉米油中, 混合均匀。

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注射用配方 4: DMSO : 20% SBE-β-CD in Saline = 10 : 90 [如：100 μL DMSO → 900 μL (20% SBE-β-CD in Saline)]
*20% SBE-β-CD in Saline的制备（4°C，储存1周）：将2g SBE-β-CD (磺丁基-β-环糊精) 溶解于10mL生理盐水中，得到澄清溶液。
注射用配方 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (如： 500 μL 2-Hydroxypropyl-β-cyclodextrin (羟丙基环胡精)→ 500 μL Saline)
注射用配方 6: DMSO : PEG300 : Castor oil : Saline = 5 : 10 : 20 : 65 (如： 50 μL DMSO → 100 μL PEG300 → 200 μL Castor oil → 650 μL Saline)
注射用配方 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (如： 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
注射用配方 8: 溶解于Cremophor/Ethanol (50 : 50), 然后用生理盐水稀释。
注射用配方 9: EtOH : Corn oil = 10 : 90 (如： 100 μL EtOH → 900 μL Corn oil)
注射用配方 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (如： 100 μL EtOH → 400 μL PEG300 → 50 μL Tween 80 → 450 μL Saline)

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口服配方 1: 悬浮于0.5% CMC Na (羧甲基纤维素钠)
口服配方 2: 悬浮于0.5% Carboxymethyl cellulose (羧甲基纤维素)
示例: 以口服配方 1 (悬浮于 0.5% CMC Na)为例说明, 如果要配制 100 mL 2.5 mg/mL 的工作液, 您可以先取0.5g CMC Na并将其溶解于100mL ddH2O中，得到0.5%CMC-Na澄清溶液；然后将250 mg待测化合物加到100 mL前述 0.5%CMC Na溶液中，得到悬浮液。

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口服配方 3: 溶解于 PEG400 (聚乙二醇400)
口服配方 4: 悬浮于0.2% Carboxymethyl cellulose (羧甲基纤维素)
口服配方 5: 溶解于0.25% Tween 80 and 0.5% Carboxymethyl cellulose (羧甲基纤维素)
口服配方 6: 做成粉末与食物混合

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注意: 以上为较为常见方法，仅供参考， InvivoChem并未独立验证这些配方的准确性。具体溶剂的选择首先应参照文献已报道溶解方法、配方或剂型，对于某些尚未有文献报道溶解方法的化合物，需通过前期实验来确定（建议先取少量样品进行尝试），包括产品的溶解情况、梯度设置、动物的耐受性等。

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请根据您的实验动物和给药方式选择适当的溶解配方/方案：
1、请先配制澄清的储备液(如：用DMSO配置50 或 100 mg/mL母液(储备液));
2、取适量母液，按从左到右的顺序依次添加助溶剂，澄清后再加入下一助溶剂。以 下列配方为例说明 (注意此配方只用于说明，并不一定代表此产品 的实际溶解配方):
10% DMSO → 40% PEG300 → 5% Tween-80 → 45% ddH2O (或 saline);
假设最终工作液的体积为 1 mL, 浓度为5 mg/mL: 取 100 μL 50 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀/澄清；向上述体系中加入50 μL Tween-80，混合均匀/澄清；然后继续加入450 μL ddH2O (或 saline)定容至 1 mL；
3、溶剂前显示的百分比是指该溶剂在最终溶液/工作液中的体积所占比例;
4、 如产品在配制过程中出现沉淀/析出，可通过加热(≤50℃)或超声的方式助溶;
5、为保证最佳实验结果，工作液请现配现用！
6、如不确定怎么将母液配置成体内动物实验的工作液，请查看说明书或联系我们;
7、 以上所有助溶剂都可在 Invivochem.cn网站购买。