RNA polymerase

Rifampicin (200, 400 mg/kg) can cause fatty liver at high concentration. In vivo treatment of S464P biofilms with rifampicin (30 mg/kg, i.p.) causes a slight decrease, but earlier rebinds in bioluminescence from these catheters in comparison to the parental signal; in contrast, rifampicin has no effect on bioluminescence in mice infected with mutant H481Y.

Absorption, Distribution and Excretion
Well absorbed from gastrointestinal tract.
Less than 30% of the dose is excreted in the urine as rifampin or metabolites.
0.19 +/- 0.06 L/hr/kg [300 mg IV]
0.14 +/- 0.03 L/hr/kg [600 mg IV]
Rifampin is distributed throughout the body and is present in effective concentrations in many organs and body fluids, including the CSF. This is perhaps best exemplified by the fact that the drug may impart an orange-red color to the urine, feces, saliva, sputum, tears, and sweat ... .
Up to 30% of a dose of the drug is excreted in the urine and 60% to 65% in the feces; less than half of this may be unaltered antibiotic.
The oral administration of rifampin produces peak concentrations in plasma in 2 to 4 hours; after ingestion of 600 mg this value is about 7 ug/mL, but there is considerable variability
Following absorption from the gastrointestinal tract, rifampin is eliminated rapidly in the bile, and an enterohepatic circulation ensues.
For more Absorption, Distribution and Excretion (Complete) data for RIFAMPIN (10 total), please visit the HSDB record page.

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Metabolism / Metabolites
Primarily hepatic, rapidly deacetylated.
The effects of rifampicin ... and phenobarbital ... on the metabolic fate of isoniazid ... and hydrazine ... were studied in rats. Male Wistar rats were fasted and injected with rifampicin at 30 mg/kg ip for 6 days, or with phenobarbital at 50 mg/kg for 3 days as pretreatment. After pretreatment, the rats were injected with isoniazid at 40 mg/kg ip. Twenty four hour urine samples were collected, and urinary concentrations of hydrazine and acetylhydrazine ... were determined by gas chromatography/mass spectrometry. The rats were /sacrificed/, livers were immediately perfused in situ and homogenized, and hepatic distribution of metabolites was determined. Separately, blood was sampled and plasma hydrazine concn were determined at 0.5, 1, 2, 3, and 4 hr after a jugular injection of 5 mg/kg hydrazine. Within 1 hr after injection of isoniazid, hydrazine and acetylhydrazine were detected in the liver and plasma. The concn of hydrazine in rifampicin or phenobarbital pretreated groups were significantly lower than those in the control group; the concn of acetylhydrazine were not altered. Pretreatment with rifampicin or phenobarbital resulted in a marked incr in the urinary elimination of hydrazine. ...
In guinea pigs, rabbits and humans, major metabolite of rifampicin in urine and bile is 25-o-deacetyl rifampicin; in body fluids of dogs and rats an unidentified metabolite has been detected.
Rifampin is metabolized in the liver to a deacetylated derivative which also possesses antibacterial activity.
Several fast growing Mycobacterium strains were found to inactivate rifampin. Two inactivated compounds (RIP-Ma and RIP-Mb) produced by these organisms were different from previously reported derivatives, i.e., phosphorylated or glucosylated derivatives, of the antibiotic. The structures of RIP-Ma and RIP-Mb were determined to be those of 3-formyl-23-[O-(alpha-D-ribofuranosyl)]rifamycin SV and 23-[O-(alpha-D-ribofuranosyl)]rifampin, respectively. To our knowledge, this is the first known example of ribosylation as mechanism of antibiotic inactivation.

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Biological Half-Life
3.35 (+/- 0.66) hours
The half-life of rifampin varies from 1.5 to 5 hours and is increased in the presence of hepatic dysfunction; it may be decreased in patients receiving isoniazid concurrently who are slow inactivators of this drug. The half-life of rifampin is progressively shortened by about 40% during the first 14 days of treatment, owing to induction of hepatic microsomal enzymes with acceleration of deacetylation of the drug.
The plasma half-life of rifampin in children 6-58 months of age averages 2.9 hours following oral administration of a single 10 mg/kg dose of the drug. Plasma half-life of the drug in children 3 months to 12.8 years of age following IV doses of the drug was 1.04-3.81 hours during the first few days of therapy and decreased to 1.17-3.19 hours after 5-14 days of therapy.

Toxicity Summary
IDENTIFICATION: Rifampicin is an antibiotic used to treat tuberculosis. Rifampicin is a semisynthetic derivative of rifamycin antibiotics which are produced by the fermentation of a strain of Streptomyces mediterranei. The fermentation produces rifamycin B. Rifamycin B is transformed by a series of synthesis reactions. Color: Red to orange odorless powder. It is very slightly soluble in water, acetone, carbon tetrachloride, alcohol and ether. It is freely soluble in chloroform, DMSO; soluble in ethyl acetate and methyl alcohol and tetrahydrofuran. Solubility in aqueous solutions is increased at acidic pH. Melting point 138 to 188 °C. Rifampicin has 2 pKa since it is a Zwitterion, pKa 1.7 related to 4-hydroxy and pKa 7.9 related to 3-piperazine nitrogen. A 1% suspension in water has pH 4.5 to 6.5. Indications: The primary indications for rifampicin are for treatment of tuberculosis (pulmonary and extrapulmonary lesions) and for leprosy. It is also useful for elimination of Neisseria meningococci in carriers (but not recommended for active meningococcal infection) and for Gram positive (Staphylococcus aureus and epidermidis, Streptococcus pyogenes, viridans and pneumoniae) and gram negative bacteria (Hemophilus influenzae type B). It has some anti-chlamydial activity and in vitro activity against some viruses (poxvirus and adenovirus) at high doses. It has recently been used for brucellosis. HUMAN EXPOSURE: Main risks and target organs: The main target organs are the liver and the gastrointestinal system. Risks of concern are toxic hepatitis with elevation of bile and bilirubin concentrations, anaemia, leukopenia, thrombocytopenia and bleeding. Summary of clinical effects: Some clinical manifestations of overdosage are extension of adverse effects. During therapy, rifampicin is usually well tolerated, however, adverse side-effects are common in intermittent rifampicin intake. These include febrile reaction, eosinophilia, leukopenia, thrombocytopenia, purpura, hemolysis and shock, hepatotoxicity and nephrotoxicity. Gastrointestinal adverse reactions may be severe leading to pseudomembranous colitis. Neurotoxic effects include confusion, ataxia, blurring of vision, dizziness and peripheral neuritis. A common toxic effect is red skin with orange discoloration of body fluids. Fatalities from adverse reactions have been reported. Rifampicin has shown no significant effects on the human fetus. It diffuses into milk and other body fluids. Contraindications: Rifampicin is contraindicated in known cases of hypersensitivity to the drug. It may be contraindicated in pregnancy (because of teratogenicity noted in animal studies and since the effects of drugs on fetus has not been established) except in the presence of a disease such as severe tuberculosis. It is contraindicated in alcoholics with severely impaired liver function and with jaundice. Routes of entry: Oral: This is the common route of entry. Eye: Use for ocular chlamydial infection treatment. Parenteral: Rifampicin may be given intravenously. Kinetics: Absorption by route of exposure: Rifampicin is readily absorbed from the gastrointestinal tract (90%). Peak plasma concentration occurs at 1.5 to 4 hours after an oral dose. Food may reduce and delay absorption. Distribution by route of exposure: Intravenous rifampicin has the same distribution as in oral route. Eighty nine percent of rifampicin in circulation is bound to plasma proteins. It is lipid soluble. It is widely distributed in body tissues and fluids. When the meninges are inflamed, rifampicin enters the cerebrospinal fluid. It reaches therapeutic levels in the lungs, bronchial secretions, pleural fluid, other cavity fluids, liver, bile, and urine. Rifampicin has a high degree of placental transfer with a fetal to maternal serum level ratio of 0.3. It is distributed into breast milk. The apparent volume of distribution (VD) is 0.93 to 1.6 L/kg. Biological half-life by route of exposure: The biological half-life is three hours range (2 to 5 hours). This half-life increases with single high doses or with liver disease. The half-life decreases by 40% during the first two weeks of therapy because of enhanced biliary excretion and induction of its own metabolism. Plasma half-life may decrease after repeated administration. The half-life of rifampicin decreased from 3.5 hours at start of therapy to 2 hours after daily administration for 1 to 2 weeks, and remained constant thereafter. Plasma half-life shortens to 1.8 to 3.1 hours in the presence of anemia. Metabolism: Approximately 85% of rifampicin is metabolised by the liver microsomal enzymes to its main and active metabolite-deacetylrifampicin. Rifampicin undergoes enterohepatic recirculation but not the deacetylated form. Rifampicin increases its own rate of metabolism. Rifampicin may also be inactivated in other parts of the body. Formylrifampicin is a urinary metabolite that spontaneously forms in the urine. Elimination by route of exposure: Rifampicin metabolite deacetylrifampicin is excreted in the bile and also in the urine. Approximately 50% of the rifampicin dose is eliminated within 24 hours and 6 to 30% of the drug is excreted unchanged in the urine, while 15% is excreted as active metabolite. Approximately 43 to 60% of oral dose is excreted in the feces. Intrinsic total body clearance is 3.5 (+/- 1.6) mL/min/kg, reduced in kidney failure. Renal clearance is 8.7 mL/min/kg. Rifampicin levels in the plasma are not significantly affected by haemodialysis or peritoneal dialysis. Rifampicin is excreted in breastmilk (1 to 3 ug/ml). Mode of action: Toxicodynamics: Rifampicin causes cholestasis at both the sinusoids and canaliculi of the liver because of defect in uptake by hepatocytes and defect in excretion, respectively. Rifampicin may produce liver dysfunction. Hepatitis occurs in 1% or less of patients, and usually in the patient with pre-existing liver disease. Hypersensitivity reactions may occur, usually characterized by a "flu" type syndrome. Nephrotoxicity appears to be related to a hypersensitivity reaction and usually occurs after intermittent or interrupted therapy. It has been suggested that some of the adverse effects associated with rifampicin may be attributed to its metabolite desacetylrifampicin. It is lipid soluble, and thus can reach and kill intracellular, as well as extracellular, Mycobacteria. Rifampicin does not bind to mammalian nuclear RNA polymerase and therefore does not affect the RNA synthesis in human beings. Rifampicin, however, may affect mammalian mitochondrial RNA synthesis at a concentration that is 100 times higher than that which affects bacterial RNA synthesis. Pharmacodynamics: Rifampicin has high activity against mycobacterial organisms, including Mycobacterium tuberculosis and M.leprae. It is also active against Staphylococcus aureus, coagulase negative staphylocci, Listeria monocytogenes, Neisseria meningitidis, Haemophilus influenzae, Legionella spp., Brucella, some strains of Escherichia coli, Proteus mirabilis, anaerobic cocci, Clostridium spp., and Bacteroides. Rifampicin is also reported to exhibit an immunosuppressive effect which has been seen in some animal experiments, but this may not be clinically significant in humans. Rifampicin may be bacteriostatic or bactericidal depending on the concentration of drug attained at site of infection. The bactericidal actions are secondary to interfering with the synthesis of nucleic acids by inhibiting bacterial DNA-dependent RNA polymers at the B-subunit thus preventing initiation of RNA transcription, but not chain elongation. Carcinogenicity: One report showed that nasopharyngeal lymphoma may develop after therapy of two years for Pott's disease. This was probably secondary to the immunosuppressive effects of rifampicin. An increase of hepatomas in female mice has been reported in one strain of mice,following one year's administration of rifampicin at a dosage of 2 to 10% of the maximum human dosage. Because of only limited evidence available for the carcinogenicity of rifampicin in mice and the absence of epidemiological studies, no evaluation of the carcinogenicity of rifampicin to humans could be made. Teratogenicity: Malformation and death have been reported in infants born to mothers exposed to rifampicin, although it was the same frequency as in the general population. Interactions: Food lowers peak blood levels because of interference with absorption of rifampicin. Antacids containing aluminium hydroxide reduced the bioavailability of rifampicin. Para-amino salicylic acid granules may delay rifampicin absorption (because of bentonite present as a granule excipient) which leads to an inadequate serum level of rifampicin. These two drugs should be given 8 to 12 hours apart. Isoniazid and rifampicin interaction has led to hepatotoxicity. (Note: slow acetylators of isoniazid have accelerated rifampicin clearance). Alcohol intake with rifampicin increases the risk for hepatotoxicity. Rifampicin induces microsomal enzymes of the liver and therefore accelerates metabolism of some drugs, beta blockers, calciferol, coumadins, cyclosporin, dapsone, diazepam, digitalis, hexobarbital, ketoconazole, methadone, oral contraceptive pills, oral hypoglycaemic agents, phenytoin, sulphasalazine, theophylline, some anti-arrhythmic drugs such as disopyramide, lorcainide, mexiletine, quinidine, and verapamil. Rifampicin induces liver steroid metabolizing enzyme thus lowering the levels of glucocorticoids and mineralocorticoids. Rifampicin lowers chloramphenicol serum levels when the two drugs are used together. When rifampicin and oral contraceptives are used concomitantly, there is decreased effectiveness of oral contraceptives because of the rapid destruction of oestrogen by rifampicin and the latter being a potent inducer of hepatic metabolising enzymes. It was reported that rifampicin may be the cause of some menstrual disorders when used with oral contraceptive pills. When rifampicin and corticosteroids are used, there is a reduction of plasma cortisol half-life and increased urinary excretion of cortisol metabolite. It may be necessary to double or quadruple the dosage of the steroid. When rifampicin and cyclosporin are taken, the serum levels of cycloserine may be lowered. In the therapy of leprosy, rifampicin may induce dapsone metabolism, however, this is of minor significance in the clinical setting. The clinical condition of patients, who are on rifampicin and also taking digoxin for heart failure, may deteriorate because of falling digoxin levels. Hence there may be a need to increase the dosage of digitalis. Another cardiac drug is disopyramide which is used for cardiac dysrhythmias, and when taken with rifampicin, there is a decrease in levels of the antiarrhythmic agent. The clinical importance of this effect has yet to be determined. Patients on methadone maintenance for narcotic detoxification may develop narcotic withdrawal when methadone plasma levels decreased as a consequence of taking rifampicin at the same time. It is also possible that rifampicin alters the distribution of methadone. Rifampicin induces hepatic enzyme metabolism which can decrease metoprolol blood levels, although this may be clinically insignificant. In patients who receive rifampicin and phenytoin together, there is an increase of clearance of phenytoin by twofold, significantly reducing the effects of the anticonvulsant drug. Modification of quinidine dose is necessary when this is used with rifampicin because of the risk of ventricular dysrhythmias. It is recommended that quinidine dosage be always readjusted when one adds or discontinues rifampicin therapy. When verapamil and rifampicin are taken together, rifampicin induces liver enzymes which increases the metabolism of the calcium channel blocker leading to undetectable verapamil levels. Rifampicin can lower the plasma calciferol (Vitamin D) level because of induction of enzyme activity. Barbiturates and salicylates decrease the activity of rifampicin. Effects with clofazimine range from no effect to decrease in the rate of absorption of rifampicin, delay in the time it reaches peak plasma concentrations, decrease in plasma rifampicin concentrations. Rifampicin can decrease the therapeutic levels of ketoconazole when given together. When rifampicin is taken with oral hypoglycemic agents (tolbutamide and chlorpropamide), these latter medications had a decrease in elimination half-lives. Rifampicin enhances antifungal actions of amphotericin B. Probenecid intake diminishes hepatic uptake of rifampicin. ANIMAL/PLANT STUDIES: Carcinogenicity: An increase of hepatomas in female mice has been reported in one strain of mice, following one year's administration of rifampicin at a dosage of 2 to 10% of the maximum human dosage. Teratogenicity: Teratogenic effects noted in rodents treated with high doses 100 to 150 mg/kg bodyweight daily in rodents have been reported to cause cleft palate and spina bifida. Rifampicin is teratogenic for rats and mice. Mutagenicity: The available studies on mutagenicity indicate an absence of mutagenic effect.

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Interactions
Interaction between ethambutol and rifampicin (rifampin) may have caused occurrence of overt Stevens-Johnson syndrome in 40 yr old male tuberculosis patient.
Concurrent daily consumption of alcohol may increase the risk of rifampin-induced hepatotoxicity and increased metabolism of rifampin; dosage adjustment of rifampin may be necessary, and patients should be monitored closely for signs of hepatotoxicity.
Rifampin may increase metabolism of theophylline, oxtriphylline, and aminophylline by induction of hepatic microsomal enzymes, resulting in increased theophylline clearance.
Chronic use of hepatic enzyme-inducing agents prior to anesthesia, except isoflurane, may increase anesthetic metabolism, leading to increased risk of hepatotoxicity.
For more Interactions (Complete) data for RIFAMPIN (40 total), please visit the HSDB record page.

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Non-Human Toxicity Values
LD50 Rabbit oral 2.12 g/kg
LD50 Rat oral 1.72 g/kg
LD50 Mouse oral 0.885 g/kg

[1]. FASEB J . 2013 Jul;27(7):2713-22.

[2]. J Infect . 2014 Feb;68(2):116-24.

[3]. J Bacteriol . 2000 Nov;182(22):6358-65.

Therapeutic Uses
Antibiotics, Antitubercular; Enzyme Inhibitors; Leprostatic Agents; Nucleic Acid Synthesis Inhibitors
Rifampin is indicated in combination with other antituberculosis medications in the treatment of all forms of tuberculosis, including tuberculous meningitis. /Included in US product labeling/
Rifampin is indicated in the treatment of close contacts of patients with proved or suspected infection caused by Neisseria meningitidis. These contacts include other household members, children in nurseries, persons in day care centers, and closed populations, such as military recruits. Health care providers who have intimate exposure (e.g., mouth-to-mouth resuscitation) with index cases also should receive prophylactic therapy. /Included in US product labeling/
Rifampin is used in the treatment of close contacts of patients with proved or suspected infections caused by Hemophilus influenza type b if at least one of the contacts is 4 years of age or younger. A close contact is defined as one who has spent 4 or more hours per day for five of the seven most recent days with the index case. /NOT included in US product labeling/
For more Therapeutic Uses (Complete) data for RIFAMPIN (7 total), please visit the HSDB record page.

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Drug Warnings
Severe hepatic injuries, including some fatalities, have been reported in patients receiving regimens that contain both rifampin and pyrazinamide for the treatment of latent tuberculosis infection. Between October 2000 and June 2003, the US CDC received a total of 48 reports of severe hepatic injury (i.e., hospitalization or death) in patients with latent tuberculosis infection receiving a rifampin and pyrazinamide regimen; there were 11 fatalities. In many fatal cases, onset of hepatic injury occurred during the second month of the 2 month regimen. Some patients who died were receiving the rifampin and pyrazinamide regimen because they previously experienced isoniazid-associated hepatitis and some had risk factors for chronic liver disease (e.g., serologic evidence of previous hepatitis A or B infection, idiopathic nonalcoholic steatotic hepatitis, alcohol or parenteral drug abuse, concomitant use of other drugs associated with idiosyncratic hepatic injury). Although data are limited, there is no evidence to date that HIV-infected individuals receiving this regimen are at any increased risk for severe hepatitis. There is evidence that the rate of severe liver injury and death related to the use of rifampin and pyrazinamide are higher than the rates reported for isoniazid-associated liver injury in the treatment of latent tuberculosis infection. Based on these reports, rifampin and pyrazinamide regiments should be used for the treatment of latent tuberculosis only when the potential benefits outweigh the risk of liver injury and death.
Rifampin has caused transient increases in serum concentrations of AST (SGOT), ALT (SGPT), bilirubin, and alkaline phosphatase. Asymptomatic jaundice which subsided without discontinuance of the drug has occurred occasionally. However, hepatitis and fatalities associated with jaundice have been reported in patients with preexisting liver disease or in those who received other hepatotoxic agents concomitantly with rifampin. Rarely, hepatitis or a shocklike syndrome with hepatic involvement with abnormal liver function test results (thought to be allergic in nature) have been reported.
Pregnancy risk category: C /RISK CANNOT BE RULED OUT. Adequate, well controlled human studies are lacking, and animal studies have shown risk to the fetus or are lacking as well. There is a chance of fetal harm if the drug is given during pregnancy; but the potential benefits may outweigh the potential risk./
In some animal experiments, an immunosuppressive effect has been observed, but this appears to have no clinical significance..
For more Drug Warnings (Complete) data for RIFAMPIN (21 total), please visit the HSDB record page.

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Pharmacodynamics
Rifampin is an antibiotic that inhibits DNA-dependent RNA polymerase activity in susceptible cells. Specifically, it interacts with bacterial RNA polymerase but does not inhibit the mammalian enzyme. It is bactericidal and has a very broad spectrum of activity against most gram-positive and gram-negative organisms (including Pseudomonas aeruginosa) and specifically Mycobacterium tuberculosis. Because of rapid emergence of resistant bacteria, use is restricted to treatment of mycobacterial infections and a few other indications. Rifampin is well absorbed when taken orally and is distributed widely in body tissues and fluids, including the CSF. It is metabolized in the liver and eliminated in bile and, to a much lesser extent, in urine, but dose adjustments are unnecessary with renal insufficiency.

C43H58N4O12

822.94

822.405

C, 62.76; H, 7.10; N, 6.81; O, 23.33

13292-46-1

135398735

Red to orange platelets from acetone
Red-brown crystalline powder

1.3±0.1 g/cm3

1004.4±65.0 °C at 760 mmHg

183ºC (dec.)

561.3±34.3 °C

0.0±0.3 mmHg at 25°C

1.613

1.09

6

15

5

59

1620

9

O(C(C([H])([H])[H])=O)[C@]1([H])[C@]([H])(C([H])([H])[H])[C@]([H])(C([H])=C([H])O[C@]2(C([H])([H])[H])C(C3C4=C(C(/C(/[H])=N/N5C([H])([H])C([H])([H])N(C([H])([H])[H])C([H])([H])C5([H])[H])=C(C(=C4C(=C(C([H])([H])[H])C=3O2)O[H])O[H])N([H])C(C(C([H])([H])[H])=C([H])C([H])=C([H])[C@]([H])(C([H])([H])[H])[C@@]([H])([C@@]([H])(C([H])([H])[H])[C@]([H])([C@@]1([H])C([H])([H])[H])O[H])O[H])=O)O[H])=O)OC([H])([H])[H] |c:18,83,t:79|

JQXXHWHPUNPDRT-WLSIYKJHSA-N

InChI=1S/C43H58N4O12/c1-21-12-11-13-22(2)42(55)45-33-28(20-44-47-17-15-46(9)16-18-47)37(52)30-31(38(33)53)36(51)26(6)40-32(30)41(54)43(8,59-40)57-19-14-29(56-10)23(3)39(58-27(7)48)25(5)35(50)24(4)34(21)49/h11-14,19-21,23-25,29,34-35,39,49-53H,15-18H2,1-10H3,(H,45,55)/b12-11+,19-14+,22-13-,44-20+/t21-,23+,24+,25+,29-,34-,35+,39+,43-/m0/s1

[(7S,9E,11S,12R,13S,14R,15R,16R,17S,18S,19E,21Z)-2,15,17,27,29-pentahydroxy-11-methoxy-3,7,12,14,16,18,22-heptamethyl-26-[(E)-(4-methylpiperazin-1-yl)iminomethyl]-6,23-dioxo-8,30-dioxa-24-azatetracyclo[23.3.1.14,7.05,28]triaconta-1(29),2,4,9,19,21,25,27-octaen-13-yl] acetate

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)

Solubility in Formulation 1: 2.5 mg/mL (3.04 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.5 mg/mL (3.04 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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 (Please use freshly prepared in vivo formulations for optimal results.)