The target of Clindamycin hydrochloride monohydrate is the 50S subunit of the bacterial ribosome, which inhibits bacterial protein synthesis [1]

1. Inhibition of hemolysin production in inducible clindamycin-resistant S. aureus (Reference [1]): Clindamycin hydrochloride monohydrate (0.125, 0.25, 0.5 μg/mL) was incubated with inducible clindamycin-resistant S. aureus strains (e.g., USA300, MRSA 252) for 24 hours. The hemolytic activity of bacterial culture supernatants was measured by incubating with sheep red blood cells. At 0.25 μg/mL, the hemolytic activity was reduced by 50% compared to the untreated control; at 0.5 μg/mL, the reduction reached 70% [1]
2. Suppression of virulence gene expression (Reference [1]): Quantitative PCR (qPCR) analysis showed that Clindamycin hydrochloride monohydrate (0.25 μg/mL) downregulated the mRNA expression of S. aureus virulence genes. Specifically, the expression of hla (hemolysin A) was reduced by 3.1-fold, spa (protein A) by 2.3-fold, and sea (staphylococcal enterotoxin A) by 2.8-fold compared to the control. This suppression was concentration-dependent, with 0.5 μg/mL leading to a 4.2-fold downregulation of hla [1]
3. Reduction of biofilm formation (Reference [1]): Clindamycin hydrochloride monohydrate (0.125-0.5 μg/mL) inhibited biofilm formation by inducible clindamycin-resistant S. aureus. After 48 hours of incubation, crystal violet staining showed that biofilm biomass was reduced by 35% (0.125 μg/mL), 48% (0.25 μg/mL), and 62% (0.5 μg/mL) compared to the untreated group [1]
4. No bactericidal effect on resistant strains (Reference [1]): Broth microdilution assay showed that Clindamycin hydrochloride monohydrate (up to 1 μg/mL) did not reduce the viable count of inducible clindamycin-resistant S. aureus (viable count remained >10⁶ CFU/mL after 24 hours), indicating it only suppressed virulence without bactericidal activity against these resistant strains [1]

1. Hemolysin activity assay (Reference [1]): Prepare bacterial culture supernatants from Clindamycin hydrochloride monohydrate-treated (0.125-0.5 μg/mL) and untreated S. aureus. Mix 100 μL of supernatant with 100 μL of 2% sheep red blood cell suspension in PBS. Incubate at 37°C for 1 hour, then centrifuge at 1000×g for 5 minutes. Measure the absorbance of the supernatant at 540 nm. Hemolytic activity is expressed as a percentage relative to the untreated control (set to 100%) [1]
2. Biofilm quantification assay (Reference [1]): Seed S. aureus (1×10⁶ CFU/mL) into 96-well plates containing Clindamycin hydrochloride monohydrate (0.125-0.5 μg/mL). Incubate at 37°C for 48 hours. Aspirate the medium, wash wells with PBS twice, and fix biofilms with 4% paraformaldehyde for 15 minutes. Stain with 0.1% crystal violet for 30 minutes, wash to remove excess stain, and elute with 33% acetic acid. Measure absorbance at 595 nm to quantify biofilm biomass [1]

1. Bacterial culture and drug treatment (Reference [1]): Inducible clindamycin-resistant S. aureus strains were cultured in Tryptic Soy Broth (TSB) at 37°C with shaking (200 rpm) to mid-log phase (OD600 = 0.6). Clindamycin hydrochloride monohydrate was added to final concentrations of 0.125, 0.25, and 0.5 μg/mL, and cultures were incubated for an additional 24 hours. Untreated cultures served as controls [1]
2. Virulence gene qPCR assay (Reference [1]): Total RNA was extracted from drug-treated and untreated S. aureus using an RNA extraction kit. cDNA was synthesized from 1 μg of total RNA with reverse transcriptase. qPCR was performed using SYBR Green Master Mix and specific primers for hla, spa, sea, and 16S rRNA (internal control). Reaction conditions: 95°C for 10 minutes, followed by 40 cycles of 95°C for 15 seconds and 60°C for 1 minute. Relative gene expression was calculated using the 2^(-ΔΔCt) method [1]
3. Viable count assay (Reference [1]): Serial dilutions of drug-treated and untreated S. aureus cultures were prepared in PBS. 100 μL of each dilution was spread on Tryptic Soy Agar (TSA) plates and incubated at 37°C for 24 hours. Colonies were counted, and viable counts were expressed as CFU/mL [1]

Absorption, Distribution and Excretion
Absorption is nearly complete, approximately 90%, with a mean peak serum concentration (Cmax) of 2.50 µg/mL and a time to peak concentration of 0.75 hours (Tmax). Oral bioavailability is approximately 11 µg•hr/mL. AUC after an oral dose of 300 mg. Plasma concentrations observed after vaginal administration are 40 to 50 times lower than those observed after parenteral administration; the peak plasma concentration (Cmax) observed after vaginal cream administration is only 0.1% of that observed after parenteral administration. Systemic exposure after vaginal suppository administration: Primarily excreted in urine, 3.6% in feces, and the remainder as inactive metabolites. Approximately 10% of clindamycin's biological activity is excreted. Widely distributed throughout the body, including bones, but not in cerebrospinal fluid. The estimated volume of distribution of clindamycin is between 43 and 74 liters.
Estimated volume of distribution is 12.3-17.4 L/h; the volume of distribution is reduced in patients with cirrhosis and altered in patients with anemia.
It is almost completely absorbed after oral administration. Peak plasma concentrations of 2-3 μg/mL are reached within 1 hour after taking 150 mg. The presence of food in the stomach does not reduce absorption. The half-life is approximately 2.9 hours; therefore, if taken every 6 hours, the accumulation of the drug is not expected to be significant. This antibiotic is widely distributed in various body fluids and tissues, including bone. Even in meningitis, clindamycin does not reach significant concentrations in cerebrospinal fluid. Concentrations sufficient to treat cerebral toxoplasmosis can be achieved. The drug readily crosses the placental barrier. 90% or more of clindamycin is bound to plasma proteins. Clindamycin can accumulate in polymorphonuclear leukocytes, alveolar macrophages, and abscesses.
In patients with severely impaired renal function, its half-life is only slightly prolonged. Clindamycin is distributed in various body fluids and tissues, including saliva, ascites, pleural fluid, synovial fluid, bone, and bile. However, even in cases of meningitis, only a small amount of the drug diffuses into the cerebrospinal fluid. Its concentrations in synovial fluid and bone are reported to be approximately 60-80% of the corresponding serum concentrations; joint inflammation does not appear to affect its permeability. Clindamycin readily crosses the placenta; its concentrations in umbilical cord blood are reported to be approximately 46% of the corresponding maternal blood concentrations. Clindamycin is distributed into breast milk. For more complete data on the absorption, distribution, and excretion of clindamycin (24 metabolites), please visit the HSDB records page.

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Metabolism/Metabolites
Clindamycin is primarily metabolized in the liver via CYP3A4, with less metabolic activity via CYP3A5. Two inactive metabolites have been identified: the oxidative metabolite clindamycin sulfoxide and the N-demethylated metabolite N-demethylclindamycin. Clindamycin is partially metabolized into biologically active and non-biologically active metabolites. The main biologically active metabolites are clindamycin sulfoxide and N-demethylclindamycin, which are excreted in urine, bile, and feces. Within 24 hours of oral administration of clindamycin, approximately 10% is excreted in urine, 3.6% is excreted in feces as the active drug and its metabolites, and the remainder is excreted as inactive metabolites. Clindamycin is primarily excreted unchanged in urine, with a small amount present in feces. Only about 10% of clindamycin is absorbed… it is inactivated by metabolism into N-demethylclindamycin and clindamycin sulfoxide, both of which are excreted in urine and bile. Known human metabolites include N-demethylclindamycin and clindamycin sulfoxide. Biological Half-Life: Approximately 3 hours in adults and approximately 2.5 hours in children. This is the elimination half-life of clindamycin. The half-life is prolonged to approximately 4 hours in the elderly. The serum half-life of clindamycin in adults and children with normal renal function is 2-3 hours. In patients with significantly impaired renal or hepatic function, the serum half-life is slightly prolonged. The serum half-life in newborns depends on gestational age, chronological age, and weight. The mean half-life for preterm and full-term newborns is 8.7 hours and 3.6 hours, respectively, while the half-life for infants aged 4 weeks to 1 year is approximately 3 hours. The serum half-life of clindamycin in infants weighing less than 3.5 kg is longer than that in heavier infants. The serum half-life of clindamycin has been reported to be approximately 2.9 hours. After intravaginal administration of 2% clindamycin cream, the systemic half-life of the drug is approximately 1.5-2.6 hours. After intravaginal administration of clindamycin suppositories, the apparent elimination half-life is approximately 11 hours on average (range: 4-35 hours).

Interactions
Calcium and neostigmine can reverse antibiotic-induced phrenic-hemiaphragmatic paralysis in mice. Concomitant use with oral clindamycin may significantly delay the absorption of oral clindamycin; concomitant use should be avoided, or patients are advised to take an adsorbent antidiarrheal at least 2 hours before or 3 to 4 hours after oral clindamycin. Concomitant use of antidiarrheals containing kaolin or attapulgite is also discouraged. In vitro experimental evidence suggests an antagonistic effect between erythromycin and clindamycin. Clindamycin has been reported to antagonize the bactericidal activity of aminoglycoside antibiotics in vitro, and some clinicians recommend against concomitant use of these drugs with clindamycin. However, in vivo antagonism has not been confirmed, and clindamycin has been successfully used in combination with aminoglycoside antibiotics without a significant decrease in activity. For more complete data on interactions of clindamycin (7 types), please visit the HSDB record page.

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Non-human toxicity values
Rat subcutaneous injection LD50: 2618 mg/kg
Rat oral LD50: 2619 mg/kg (clindamycin hydrochloride)
Mouse intraperitoneal injection LD50: 361 mg/kg (clindamycin hydrochloride)
Swiss mouse intraperitoneal injection LD50: 1145 mg/kg (clindamycin phosphate)
Swiss mouse intravenous injection LD50: 855 mg/kg (clindamycin phosphate)

[1]. Clindamycin suppresses virulence expression in inducible clindamycin-resistant Staphylococcus aureus strains. Ann Clin Microbiol Antimicrob. 2018 Oct 20;17(1):38.

Therapeutic Uses

Antibacterial Agents
Clindamycin: For use in the vagina (as a cream or suppository) or orally, to treat bacterial vaginosis (formerly known as Haemophilus vaginitis, Gardnerella vaginitis, nonspecific vaginitis, Corynebacterium vaginitis, or anaerobic vaginitis). /Included in the US product label/
Clindamycin Phosphate: For topical use alone or in combination with benzoyl peroxide, to treat inflammatory acne vulgaris. /Clindamycin Phosphate; Included in the US product label/
Clindamycin Phosphate: For parenteral administration, to treat bone and joint infections (including acute hematogenous osteomyelitis) caused by Staphylococcus aureus, and as adjunctive therapy to surgery for chronic bone and joint infections caused by susceptible bacteria. Clindamycin may also be used orally or parenterally to treat severe respiratory infections, skin and soft tissue infections, or sepsis caused by Staphylococcus aureus, Streptococcus pneumoniae, or other streptococci (excluding Enterococcus faecalis) susceptible to clindamycin. /US Product Labels Contain/
For more complete data on the therapeutic uses of clindamycin (23 types), please visit the HSDB record page.

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Drug Warnings
/Black Box Warning/ Almost all antimicrobial drugs, including clindamycin hydrochloride, have been reported to cause Clostridium difficile-associated diarrhea (CDAD), ranging in severity from mild diarrhea to fatal colitis. CDAD alters the normal flora of the colon, leading to Clostridium difficile overgrowth. Treatment with antimicrobial drugs is necessary. Clindamycin has been associated with potentially fatal severe colitis and should therefore be used only for severe infections where less toxic antimicrobial drugs are not suitable. Because clindamycin treatment… should not be used in patients with non-bacterial infections, such as most upper respiratory tract infections. It produces toxins A and B, which can cause Clostridium difficile-associated diarrhea (CDAD) caused by Clostridium difficile. Clostridium difficile infections increase morbidity and mortality because these infections may be unresponsive to antimicrobial treatment and may require colectomy. All patients who develop diarrhea after antibiotic use should be considered for highly toxic Clostridium difficile strains. Because CDAD has been reported to occur two months after antibiotic use, CDAD screening is necessary. A thorough medical history should be taken. If CDAD is suspected or confirmed, antibiotics not specifically targeting Clostridium difficile may need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibiotic treatment for Clostridium difficile infection, and surgical evaluation should be administered according to clinical indications. Dry skin and erythema are the most common adverse reactions to topical application of 1% clindamycin phosphate gel, lotion, or solution. In clinical studies evaluating 1% clindamycin phosphate topical gel, lotion, or solution, 23%, 18%, and 19% of patients reported dry skin, respectively, while 7%, 14%, and 16% reported erythema, respectively. 18%, 10%, and 1% of patients reported oily or greasy skin, respectively. 7% and 11% of patients reported oily or greasy skin, respectively. Peeling. Burning or itching has been reported in 7-11% of patients after using topical clindamycin phosphate preparations. /Clindamycin Phosphate/
It has been reported that 3.6% or 9-10.7% of non-pregnant women developed vaginitis (including vulvovaginitis, vulvovaginal disease, vaginal discharge, and trichomonal vaginitis) after using clindamycin phosphate vaginal suppositories or cream. It has been reported that 6% or 4.4% of non-pregnant women developed vulvovaginitis after 3 or 7 days of using clindamycin phosphate vaginal cream, and 3.2% or 5.3% developed vulvovaginal disease (including irritation). It has been reported that 3.4% or 1.9% of non-pregnant women developed vulvovaginal disease or vaginal pain after using clindamycin phosphate vaginal suppositories. It has been reported that the probability of developing trichomoniasis infection in non-pregnant women after 7 days of using clindamycin phosphate vaginal cream is 1.3%. The incidence rate was less than 1% in patients receiving intravaginal clindamycin treatment, and at least one patient experienced vaginal bleeding after using clindamycin phosphate vaginal cream. Other adverse reactions include vaginal discharge, uterine bleeding, urinary tract infection, pyelonephritis, dysuria, endometriosis, menstrual disorders, and vaginal pain. Clindamycin phosphate may also cause candidiasis and vaginitis (including vulvovaginitis, vulvovaginal disease, vaginal discharge, and trichomonal vaginitis). These are the most common adverse reactions to treatment with clindamycin phosphate (2% clindamycin) vaginal cream or suppositories. Clindamycin Phosphate
For more complete data on drug warnings for clindamycin (35 in total), please visit the HSDB record page.

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Pharmacodynamics
Clindamycin exerts its antimicrobial effect by inhibiting the synthesis of microbial proteins. Its time to peak concentration (Tmax) and half-life are relatively short, therefore it needs to be administered every six hours to ensure adequate antibiotic concentration. Clostridium difficile-associated diarrhea (CDAD) has been observed in patients using clindamycin, ranging in severity from mild diarrhea to fatal colitis, sometimes occurring within two months after discontinuation of antibiotic treatment. The use of antibiotics and the resulting A and B toxins contribute to morbidity and mortality in these patients. Clostridium difficile overgrowth. Due to the associated risks, clindamycin should be reserved for serious infections where less toxic antibiotics are not suitable. It is effective against a wide range of Gram-positive aerobic bacteria as well as Gram-positive and Gram-negative anaerobes. Clindamycin resistance typically arises from 23S ribosomal RNA base modification. Complete resistance exists between clindamycin and lincomycin, and cross-resistance may also exist between clindamycin and macrolide antibiotics (e.g., erythromycin) due to similarity in their binding sites. Because antimicrobial susceptibility patterns vary geographically, local susceptibility testing results should be consulted before use to ensure adequate coverage of the relevant pathogens.

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1. Clindamycin is a lincosamide antibiotic. Classification and basic mechanism: Clindamycin hydrochloride monohydrate. By binding to the 50S subunit of bacterial ribosomes, it interferes with peptide chain elongation and inhibits bacterial protein synthesis, thus exerting antibacterial effects [1]. 2. For induced clindamycin-resistant Staphylococcus aureus (carrying the erm gene, which mediates drug resistance through ribosomal methylation), clindamycin hydrochloride monohydrate may not show bactericidal or bacteriostatic activity at sub-inhibitory concentrations, but it can significantly inhibit the expression of virulence factors (such as hemolysin and enterotoxin) and biofilm formation, thereby reducing bacterial pathogenicity. Special effects on drug-resistant strains: [1] 3. Studies have shown that even if it cannot kill bacteria, clindamycin hydrochloride monohydrate may have therapeutic value for infections caused by induced clindamycin-resistant Staphylococcus aureus because it can reduce bacterial virulence and prevent disease progression. Clinical significance: This study [1]

C18H34CL2N2O5S

461.4440

478.167

C, 45.09; H, 7.57; Cl, 14.79; N, 5.84; O, 20.02; S, 6.69

58207-19-5

Clindamycin hydrochloride;21462-39-5;Clindamycin;18323-44-9

446598

Yellow, amorphous solid

647ºC at 760 mmHg

143ºC

345.1ºC

143 ° (C=2, H2O)

1.456

4

7

7

27

502

9

Cl[C@@]([H])(C([H])([H])[H])[C@]([H])([C@]1([H])[C@@]([H])([C@@]([H])([C@]([H])([C@]([H])(O1)SC([H])([H])[H])O[H])O[H])O[H])N([H])C([C@]1([H])C([H])([H])[C@@]([H])(C([H])([H])C([H])([H])C([H])([H])[H])C([H])([H])N1C([H])([H])[H])=O.Cl[H]

KWMXKEGEOADCEQ-WNNJHRBUSA-N

InChI=1S/C18H33ClN2O5S.ClH.H2O/c1-5-6-10-7-11(21(3)8-10)17(25)20-12(9(2)19)16-14(23)13(22)15(24)18(26-16)27-4;;/h9-16,18,22-24H,5-8H2,1-4H3,(H,20,25);1H;1H2/t9-,10+,11-,12+,13-,14+,15+,16+,18+;;/m0../s1

(2S,4R)-N-((1S,2S)-2-chloro-1-((2R,3R,4S,5R,6R)-3,4,5-trihydroxy-6-(methylthio)tetrahydro-2H-pyran-2-yl)propyl)-1-methyl-4-propylpyrrolidine-2-carboxamide hydrochloride hydrate

Clindamycin HCl (H2O); Clindamycin hydrochloride hydrate

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.)