Gentamicin is nontoxic to tissue culture monolayers, does not inhibit viral replication, and is a more potent in vitro bacterial inhibitor than the combination of penicillin and streptomycin [2]. Gentamicin is more effective than penicillin and streptomycin against a wider range of organisms (Pseudomonas aeruginosa, Proteus spp., and Streptococcus) and has been successfully added as an additive in commercial mycological media to inhibit bacterial growth [2]. Gentamicin is stable at autoclaving temperatures, nontoxic to rhesus kidney, HeLa, and human amnion cells, and does not interfere with the cytopathic effects of some polioviruses and echoviruses in tissue culture [2]. Several species in the genus Micromonospora produce gentamicin [3]. The major groove of the RNA A site is where gentamicin C1a binds [3].

It has been demonstrated that gentamicin, both oral and injectable, has strong antibacterial activity against Y. pestis in infection models using mice [3]. Mice treated with gentamicin (0.27 g/kg) demonstrated a substantial decrease in bacteria on foreign bodies [4].

Absorption, Distribution and Excretion
Gentamicin is excreted primarily by the kidneys. In patients with normal renal function, 70% or more of an initial gentamicin dose can be recovered in the urine within 24 hours. Excretion of gentamicin is significantly reduced in patients with renal impairment.
The renal clearance of gentamicin is comparable to individual creatinine clearance.
/MILK/ Gentamicin is distributed into milk following IM administration.
Gentamicin is distributed into cerebrospinal fluid (CSF) in low concentrations following IM or IV administration. CSF concentrations of gentamicin following intrathecal administration depend on the dose administered, the site of injection, the volume in which the dose is diluted, and the presence or absence of obstruction to CSF flow. There may be considerable interpatient variation in concentrations achieved. In one study, intrathecal administration of 4 mg of gentamicin resulted in CSF concentrations of the drug of 19-46 ug/mL for 8 hours and less than 3 ug/mL at 20 hours. Gentamicin crosses the placenta.
Following parenteral administration of usual dosages of gentamicin, the drug can be detected in lymph, subcutaneous tissue, lung, sputum, and bronchial, pleural, pericardial, synovial, ascitic, and peritoneal fluids. Concentrations in bile may be low, suggesting minimal biliary excretion. In patients with ventilator-associated pneumonia receiving IV gentamicin (240 mg once daily), drug concentrations in alveolar lining fluid were 32% of serum concentrations and averaged 4.24 ug/mL 2 hours after a dose. Only minimal concentrations of gentamicin are attained in ocular tissue following IM or IV administration.
Accumulation of gentamicin does not appear to occur in patients with normal renal function receiving 1-mg/kg doses every 8 hours for 7-10 days. However, accumulation may occur with higher doses and/or when the drug is given for prolonged periods, especially in patients with renal impairment.
For more Absorption, Distribution and Excretion (Complete) data for Gentamicin (18 total), please visit the HSDB record page.

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Metabolism / Metabolites
Gentamicin undergoes little to no metabolism.
Gentamicin is not metabolized. It is excreted by glomerular filtration in an active, unchanged form.

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Biological Half-Life
One study assessing the pharmacokinetics of gentamicin in children and adults reported a mean half-life of 75 minutes after intravenous administration. The mean half-life associated with intramuscular administration was about 29 minutes longer. Fever and anemia may result in a shorter half-life although dose adjustments are not usually necessary. Severe burns are also associated with a shorter half-life and may result in lower gentamicin serum concentrations.
The plasma elimination half-life of gentamicin is usually 2-4 hours in adults with normal renal function and is reported to range from 24-60 hours in adults with severe renal impairment. The serum half-life of gentamicin averages 3-3.5 hours in infants 1 week to 6 months of age and 5.5 hours in full-term infants and large premature infants less than 1 week of age. In small premature infants, the plasma half-life is approximately 5 hours in those weighing over 2 kg, 8 hours in those weighing 1.5-2 kg, and 11.5 hours in those weighing less than 1.5 kg.
... terminal elimination half-lives of greater than 100 hours have been reported in adults with normal renal function following repeated IM or IV administration of the drug.

Toxicity Summary
IDENTIFICATION AND USE: Gentamicin sulfate is an aminoglycoside antibiotic. Gentamicin is widely used in the treatment of severe infections. It is active against many strains of Gram-negative bacteria and Streptococus aureus. It is inactive against anaerobes and poorly active against Streptococus hemolyticus and Pneumococcus. HUMAN EXPOSURE AND TOXICITY: Main risks and target organs: The main toxic effects are vestibular damage, deafness and renal dysfunction. The damage on the vestibular portion of the eighth cranial nerve appears to be greater than that on the cochlear portion. The main target organs are the eighth cranial nerves and the kidneys. Damage to eighth cranial nerve (both divisions) resulting in tinnitus, deafness, nausea, vomiting, vertigo, dizziness and nystagmus, and nephrotoxicity causing acute tubular necrosis resulting in renal failure. Loss of hearing, dizziness, vertigo, ataxia, nausea, vomiting and renal impairment developing in a patient on gentamicin therapy suggests a diagnosis of gentamicin toxicity. Other toxic features are muscular paralysis and respiratory depression. As gentamicin accumulates in the renal cortex, a critical concentration is reached when the concentrating ability of the kidney becomes impaired. Nephrotoxicity appears to be related to the duration for which the trough serum concentration exceeds 2 ug/ml. The exact mechanism of toxicity is unknown. Ototoxicity and vestibular toxicity seem most highly correlated with elevated peak concentrations (greater than 10 ug/mL) of gentamicin. Gentamicin accumulates in endolymph and perilymph and progressive destruction of ventricular and cochlear cells occurs. Repeated courses of gentamicin may produce progressive destruction of cells leading to deafness. Gentamicin appears to damage the vestibular portion more than the cochlear portion. Neuromuscular blockade with acute muscular paralysis and apnea may occur rarely. Most episodes have occurred in association with anesthesia or administration of other neuromuscular blockers but may also occur after intrapleural or intraperitoneal instillation of large doses of gentamicin or other aminoglycosides. This phenomenon may occur after intravenous or intramuscular administration. ANIMAL STUDIES: Clinical signs of intoxication in rodents included convulsions, prostration, hypoactivity, polydipsia, dyspnoea and ataxia. Dogs exhibited muscle tremors, salivation, and anorexia. Histopathological examination of kidneys from dogs that died up to 13 days after dosing revealed necrosis of the proximal convoluted tubule. Groups of 3 female Rhesus monkeys were injected i.m. with doses of 0, 6 or 30 mg/kg bw/day gentamicin in an aqueous vehicle for 3 weeks. Adverse clinical signs were limited to the 30 mg/kg bw/day group, which included pronounced facial paling and ptosis, markedly disturbed equilibrium from day 20, and depressed food intake and body- weight gain from week 2 onwards. Electron microscopy of renal tubules from the 30 mg/kg bw/day monkeys revealed myeloid bodies present in both tubular cells and lumen, increased phagosomes, disappearance of brush borders and sloughing of epithelial cells from the basement membrane. Groups of beagle dogs (4/sex/group) were administered oral doses of 0, 2, 10, or 60 mg/kg bw/day gentamicin in capsules for 14 weeks. Emesis and diarrhoea were observed occasionally in treated dogs. The only postmortem change was interstitial nephritis observed in 2 animals in the high-dose group. Gentamicin had negative effects on sperm parameters and testis apoptosis in rats. No treatment-related changes in pregnancy rate, litter size and weight, prenatal mortality or fetal abnormalities were reported in 2 generation study in rats. Gentamicin was tested in vitro for its ability to induce forward gene mutation in Chinese hamster ovary cells at concentrations of 128-5000 ug/mL and chromosomal aberrations in these cells at concentrations of 800-5000 ug/mL, both with and without metabolic activation. It was also tested in vivo for its ability to induce nuclear anomalies in mouse bone-marrow cells at intravenous doses of 20-80 mg/kg bw, the highest dose being the maximum tolerated dose. There was no indication of mutagenic activity.

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Hepatotoxicity
Intravenous and intramuscular therapy with gentamicin has been linked to mild and asymptomatic elevations in serum alkaline phosphatase levels, but rarely affects aminotransferase levels or bilirubin, and changes resolve rapidly once gentamicin is stopped. Only isolated case reports of acute liver injury with jaundice have been associated with aminoglycoside therapy including gentamicin, most of which are not very convincing. The hepatic injury described in these reports is typically mixed but can evolve into a cholestatic hepatitis. The latency to onset is rapid, occurring within 1 to 3 weeks and is typically associated with skin rash, fever and sometimes eosinophilia. Recovery typically occurs within 1 to 2 months and chronic injury has not been described. Aminoglycosides are not listed or mentioned in large case series of drug induced liver disease and acute liver failure; thus, hepatic injury due to gentamicin is rare if it occurs at all.
Likelihood score: E (unlikely cause of clinically apparent liver injury).

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Effects During Pregnancy and Lactation
◉ Summary of Use during Lactation
Gentamicin is poorly excreted into breastmilk. Newborn infants apparently absorb small amounts of gentamicin, but their serum levels with three times daily dosages are far below those attained when treating newborn infections and systemic effects of gentamicin are unlikely. Older infants would be expected to absorb even less gentamicin. Because there is little variability in the milk gentamicin levels during multiple daily dose regimens, timing breastfeeding with respect to the dose is of little or no benefit in reducing infant exposure. Data are not available with single daily dose regimens. Monitor the infant for possible effects on the gastrointestinal flora, such as diarrhea, candidiasis (e.g., thrush, diaper rash) or rarely, blood in the stool indicating possible antibiotic-associated colitis.
Maternal use of an ear drop or eye drop that contains gentamicin presents little or no risk for the nursing infant.
◉ Effects in Breastfed Infants
Bloody stools in one 5-day-old infant were possibly caused by concurrent maternal administration of clindamycin and gentamicin.
A 2-month-old infant breastfed since birth. His mother had taken many medications during pregnancy, but she did not recall their identity. She developed mastitis and was treated with amoxicillin-clavulanic acid 1 gram orally every 12 hours and gentamicin 160 mg intramuscularly once daily. The infant was breastfed for 10 minutes starting 15 minutes after the first dose of both drugs. About 20 minutes later, the infant developed a generalized urticaria which disappeared after 30 minutes. A few hours later, the infant breastfed again and the urticaria reappeared after 15 minutes and disappeared after an hour. After switching to formula feeding and no further infant exposure to penicillins, the reaction did not reappear with follow-up to 16 months of age. The adverse reaction was probably caused by the antibiotics in breastmilk. The drug that caused the reaction cannot be determined, but it was most likely the amoxicillin-clavulanic acid.
◉ Effects on Lactation and Breastmilk
Relevant published information was not found as of the revision date.

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Protein Binding
Studies have determined that plasma protein binding of gentamicin is between 0-30% depending on the method of testing.

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Interactions
One in vitro study indicates that cytarabine may antagonize the activity of gentamicin against Klebsiella pneumoniae.
Gentamicin appears to be more readily inactivated by antipseudomonal penicillins (eg, ticarcillin) than amikacin both in vitro and in vivo in patients with renal failure.
Concomitant and/or sequential use of an aminoglycoside and other systemic, oral, or topical drugs that have neurotoxic, ototoxic, or nephrotoxic effects (e.g., other aminoglycosides, acyclovir, amphotericin B, bacitracin, capreomycin, certain cephalosporins, colistin, cisplatin, methoxyflurane, polymyxin B, vancomycin) may result in additive toxicity and should be avoided, if possible. /Aminoglycosides/
Because of the possibility of an increased risk of ototoxicity due to additive effects or altered serum and tissue aminoglycoside concentrations, aminoglycosides should not be given concomitantly with potent diuretics such as ethacrynic acid, furosemide, urea, or mannitol. It has been suggested that concomitant use of certain anti-emetics that suppress nausea and vomiting of vestibular origin and vertigo (e.g., dimenhydrinate, meclizine) may mask symptoms of aminoglycoside-associated vestibular ototoxicity. /Aminoglycosides/
For more Interactions (Complete) data for Gentamicin (12 total), please visit the HSDB record page.

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Non-Human Toxicity Values
LD50 Mouse im 167 mg/kg
LD50 Mouse iv 51 mg/kg
LD50 Mouse sc 274 mg/kg
LD50 Mouse ip 235 mg/kg
For more Non-Human Toxicity Values (Complete) data for Gentamicin (8 total), please visit the HSDB record page.

[1]. A rapid and sensitive method for kinetic study and activity assay of DNase I in vitro based on a GO-quenched hairpin probe. Anal Bioanal Chem. 2016 May;408(14):3801-9.

[2]. Antibacterial activity of gentamicin sulfate in tissue culture. Appl Microbiol. 1970 Dec;20(6):989-90.

[3]. Microbial biosynthesis and applications of gentamicin: a critical appraisal. Crit Rev Biotechnol. 2008;28(3):173-212.

[4]. Effect of treatment with methicillin and gentamicin in a new experimental mouse model of foreignbody infection. Antimicrob Agents Chemother. 1994 Sep;38(9):2047-53.

Therapeutic Uses
Anti-Bacterial Agents; Protein Synthesis Inhibitors
/CLINICAL TRIALS/ ClinicalTrials.gov is a registry and results database of publicly and privately supported clinical studies of human participants conducted around the world. The Web site is maintained by the National Library of Medicine (NLM) and the National Institutes of Health (NIH). Each ClinicalTrials.gov record presents summary information about a study protocol and includes the following: Disease or condition; Intervention (for example, the medical product, behavior, or procedure being studied); Title, description, and design of the study; Requirements for participation (eligibility criteria); Locations where the study is being conducted; Contact information for the study locations; and Links to relevant information on other health Web sites, such as NLM's MedlinePlus for patient health information and PubMed for citations and abstracts for scholarly articles in the field of medicine. Gentamycin is included in the database.
Gentamicin Injection is indicated in the treatment of serious infections caused by susceptible strains of the following microorganisms: Pseudomonas aeruginosa, Proteus species (indole-positive and indole-negative), Escherichia coli, Klebsiella-Enterobacter-Serratia species, Citrobacter species, and Staphylococcus species (coagulase-positive and coagulase-negative). /Included in US product label/
Gentamicin has been used effectively in combination with carbenicillin for the treatment of life-threatening infections caused by Pseudomonas aeruginosa. It has also been found effective when used in conjunction with a penicillin-type drug for the treatment of endocarditis caused by group D streptococci. /Included in US product label/
For more Therapeutic Uses (Complete) data for Gentamicin (26 total), please visit the HSDB record page.

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Drug Warnings
/BOXED WARNINGS/ Patients treated with aminoglycosides should be under close clinical observation because of the potential toxicity associated with their use. As with other aminoglycosides, Gentamicin Injection is potentially nephrotoxic. The risk of nephrotoxicity is greater in patients with impaired renal function and in those who receive high dosage or prolonged therapy. Neurotoxicity manifested by ototoxicity, both vestibular and auditory, can occur in patients treated with gentamicin, primarily in those with pre-existing renal damage and in patients with normal renal function treated with higher doses and/or for longer periods than recommended. Aminoglycoside-induced ototoxicity is usually irreversible. Other manifestations of neurotoxicity may include numbness, skin tingling, muscle twitching and convulsions. Renal and eighth cranial nerve function should be closely monitored, especially in patients with known or suspected reduced renal function at onset of therapy, and also in those whose renal function is initially normal but who develop signs of renal dysfunction during therapy. Urine should be examined for decreased specific gravity, increased excretion of protein, and the presence of cells or casts. Blood urea nitrogen (BUN), serum creatinine, or creatinine clearance should be determined periodically. When feasible, it is recommended that serial audiograms be obtained in patients old enough to be tested, particularly high-risk patients. Evidence of ototoxicity (dizziness, vertigo, tinnitus, roaring in the ears or hearing loss) or nephrotoxicity requires dosage adjustment or discontinuance of the drug. As with the other aminoglycosides, on rare occasions changes in renal and eighth cranial nerve function may not become manifest until soon after completion of therapy. Serum concentrations of aminoglycosides should be monitored when feasible to assure adequate levels and to avoid potentially toxic levels. When monitoring gentamicin peak concentrations, dosage should be adjusted so that prolonged levels above 12 ug/mL are avoided. When monitoring gentamicin trough concentrations, dosage should be adjusted so that levels above 2 ug/mL are avoided. Excessive peak and/or trough serum concentrations of aminoglycosides may increase the risk of renal and eighth cranial nerve toxicity. In the event of overdose or toxic reactions, hemodialysis may aid in the removal of gentamicin from the blood, especially if renal function is, or becomes, compromised. The rate of removal of gentamicin is considerably less by peritoneal dialysis than by hemodialysis. In the newborn infant, exchange transfusions may also be considered. Concurrent and/or sequential systemic or topical use of other potentially neurotoxic and/or nephrotoxic drugs, such as cisplatin, cephaloridine, kanamycin, amikacin, neomycin, polymyxin B, colistin, paromomycin, streptomycin, tobramycin, vancomycin, and viomycin, should be avoided. Other factors which may increase patient risk of toxicity are advanced age and dehydration. The concurrent use of gentamicin with potent diuretics, such as ethacrynic acid or furosemide, should be avoided, since certain diuretics by themselves may cause ototoxicity. In addition, when administered intravenously, diuretics may enhance aminoglycoside toxicity by altering the antibiotic concentration in serum and tissue. Aminoglycosides can cause fetal harm when administered to a pregnant woman.
Hypersensitivity to gentamicin is a contraindication to its use. A history of hypersensitivity or serious toxic reactions to other aminoglycosides may contraindicate use of gentamicin because of the known cross-sensitivity of patients to drugs in this class.
Aminoglycosides can cause fetal harm when administered to a pregnant woman. Aminoglycoside antibiotics cross the placenta, and there have been several reports of total irreversible bilateral congenital deafness in children whose mothers received streptomycin during pregnancy. Serious side effects to mother, fetus, or newborn have not been reported in the treatment of pregnant women with other aminoglycosides. It is not known whether gentamicin sulfate can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. If gentamicin is used during pregnancy or if the patient becomes pregnant while taking gentamicin, she should be apprised of the potential hazard to the fetus.
Other reported adverse reactions possibly related to gentamicin include: respiratory depression, lethargy, confusion, depression, visual disturbances, decreased appetite, weight loss, hypotension and hypertension; rash, itching, urticaria, generalized burning, laryngeal edema, anaphylactoid reactions, fever and headache; nausea, vomiting, increased salivation and stomatitis; purpura, pseudotumor cerebri, acute organic brain syndrome, pulmonary fibrosis, alopecia, joint pain, transient hepatomegaly and splenomegaly.
For more Drug Warnings (Complete) data for Gentamicin (38 total), please visit the HSDB record page.

C21H43N5O7

477.6

477.316

1403-66-3

Gentamicin sulfate;1405-41-0

3467

White amorphous powder

1.3±0.1 g/cm3

669.4±55.0 °C at 760 mmHg

358.6±31.5 °C

0.0±4.6 mmHg at 25°C

1.583

-1.89

8

12

7

33

636

0

CEAZRRDELHUEMR-UHFFFAOYSA-N

InChI=1S/C21H43N5O7/c1-9(25-3)13-6-5-10(22)19(31-13)32-16-11(23)7-12(24)17(14(16)27)33-20-15(28)18(26-4)21(2,29)8-30-20/h9-20,25-29H,5-8,22-24H2,1-4H3

2-[4,6-diamino-3-[3-amino-6-[1-(methylamino)ethyl]oxan-2-yl]oxy-2-hydroxycyclohexyl]oxy-5-methyl-4-(methylamino)oxane-3,5-diol

Septigen UromycineCenticinRefobacinOksitselanimLyramycin

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

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

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Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).

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Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)]
*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.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

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Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).

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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

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Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

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