Clindamycin phosphate Chemical Properties

Melting point:

114 °C

Boiling point:

159°C

Density 

1.41±0.1 g/cm3(Predicted)

refractive index 

122 ° (C=1, H2O)

storage temp. 

Sealed in dry,2-8°C

solubility 

DMSO: soluble224mg/mL at 25°C

form 

solid

pka

pKa 0.964±0.06 (H2O t=21) (Uncertain);6.06 ±0.06 (I=0.008)(H2O t=21) (Uncertain)

color 

White

Water Solubility 

Freely soluble in water

Merck 

14,2356

Stability:

Stable, but store cool. Incompatible with strong oxidizing agents, calcium gluconate, barbiturates, magnesium sulfate, phenytoin, B group sodium vitamins.

InChIKey

UFUVLHLTWXBHGZ-YFBDLMQENA-N

SMILES

[C@]([H])([C@]1([H])[C@@H]([C@H](O)[C@@H](OP(O)(O)=O)[C@@H](SC)O1)O)([C@@H](Cl)C)NC([C@H]1N(C[C@H](CCC)C1)C)=O |&1:0,2,4,5,7,13,18,23,26,r|

Safety Information

Hazard Codes 

Xn,Xi

Risk Statements 

22-36/37/38

Safety Statements 

36-26

WGK Germany 

3

RTECS 

GF2625000

HS Code 

29419000

MSDS

• Language:English Provider:SigmaAldrich

Clindamycin phosphate Usage And Synthesis

Description

Clindamycin phosphate is a water-soluble ester of the semisynthetic antibiotic produced by a 7 (S)-chloro-substitution of the 7 (R)-hydroxyl group of the parent antibiotic, lincomycin. It is a derivative of lincomycin(a lincosamide). It has primarily bacteriostatic action against Gram-positive aerobes and a wide range of anaerobicbacteria. It is a topical antibiotic used in the treatment of infections. These might include infections of the respiratory tract, septicaemia, peritonitis and bone infections. It is also used to treat moderate to severe acne.

Indications

Clindamycin Phosphate Topical Solution and Clindamycin Phosphate Lotion (Clindamycin Phosphate Topical Suspension USP, 1%) contain clindamycin phosphate, USP, at a concentration equivalent to 10 mg clindamycin per milliliter. Clindamycin Phosphate Gel contains clindamycin phosphate, USP, at a concentration equivalent to 10 mg clindamycin per gram.

Clindamycin Phosphate is indicated for topical application in the treatment of acne vulgaris. In view of the potential for diarrhea, bloody diarrhea and pseudomembranous colitis, the physician should consider whether other agents are more appropriate.

CLINICAL PHARMACOLOGY

Although clindamycin phosphate is inactive in vitro, rapid in vivo hydrolysis converts this compound to the antibacterially active clindamycin.
Cross resistance has been demonstrated between clindamycin and lincomycin.
Antagonism has been demonstrated between clindamycin and erythromycin.
Following multiple topical applications of clindamycin phosphate at a concentration equivalent to 10 mg clindamycin per mL in an isopropyl alcohol and water solution, very low levels of clindamycin are present in the serum (0 to 3 ng/mL) and less than 0.2% of the dose is recovered in urine as clindamycin.
Clindamycin activity has been demonstrated in comedones from acne patients. The mean concentration of antibiotic activity in extracted comedones after application of Clindamycin Phosphate Topical Solution for 4 weeks was 597 mcg/g of comedonal material (range 0 to 1,490). Clindamycin in vitro inhibits all Propionibacterium acnes cultures tested (MICs 0.4 mcg/mL). Free fatty acids on the skin surface have been decreased from approximately 14% to 2% following application of clindamycin.

Pharmacokinetics

In an open label, parallel group study of 24 patients with acne vulgaris, once-daily topical administration of approximately 3-12 grams/day of clindamycin phosphate gel for five days resulted in peak plasma clindamycin concentrations that were less than 5.5 ng/ml.
Following multiple applications of clindamycin phosphate gel less than 0.04 % of the total dose was excreted in the urine.

Biological Activity

Clindamycin 2-phosphate is an aminoglycoside antibiotic that has been used to study the cytoxicity of antibiotics on human cell lines, Bacterial protein synthesis and peptide translation, and the inhibition of human Tyrosyl-DNA Phosphodiesterase.
Clindamycin 2-phosphate is a pharmacological tyrosyl-DNA phosphodiesterase (Tdp1) inhibitor. Clindamycin 2-phosphate can repair DNA topoisomerase I-DNA covalent complexes by hydrolyzing the tyrosyl-DNA bond. It inhibits protein synthesis in bacteria by binding the 50s ribosomal subunit.  
Spectrum of Activity: Gram positive cocci and taxoplasma. Especially active against anaerobic bacteria.
Mode of Action: Inhibits protein synthesis in bacterial by binding the 50s ribosomal subunit.

Uses

Clindamycin phosphate is used topically alone or in conjunction with benzoyl peroxide in the treatment of inflammatory acne vulgaris. In weighing the potential benefits of topical clindamycin therapy, the possibility of serious adverse GI effects associated with the drug should be considered. Therapy of acne vulgaris must be individualized and frequently modified depending on the types of acne lesions which predominate and the response to therapy. Topical anti-infectives, including clindamycin, generally are effective in the treatment of mild to moderate inflammatory acne. However, use of topical anti-infectives as monotherapy may lead to bacterial resistance; this resistance is associated with decreased clinical efficacy.Topical clindamycin is particularly useful when used with benzoyl peroxide or topical retinoids. Results of clinical studies indicate that combination therapy results in a reduction in total lesion counts of 50-70%.

Drug interactions

Clindamycin has been shown to have neuromuscular blocking properties that may enhance the action of other neuromuscular blocking agents. Therefore it should be used with caution in patients receiving such agents.

Incompatibilities

Clindamycin phosphate is incompatible with natural rubber closures. Aminophylline, ampicillin, calcium gluconate, ceftriaxone, ciprofloxacin,doxapram, drotrecogin alfa (activated), fluconazole, magnesium sulfate,phenytoin sodium, ranitidine, tramadol.

Chemical Properties

solid or colorless solution with characteristic alcohol odor.

Uses

Clindamycin 2-phosphate is a a salt of clincamycin, a semi-synthetic lincosamide. The salt is prepared by selective phosphorylation of the 2-hydroxy moiety of the sugar of clindamycin. The introduction of the phosphate affords improved solubility for injectable formulations. Like other members of the lincosamide family, clindamycin 2-phosphate is a broad spectrum antibiotic with activity against anaerobic bacteria and protozoans. Clindamycin acts by binding to the 23S ribosomal subunit, blocking protein synthesis.

Preparation

Preparation of Clindamycin Phosphate: a solution of 808 mg of the phosphorylated ester in 6 ml of pyridine and 16 ml of acetic acid is stirred at ambient temperature while s5 mg of zinc is rapidly added. The mixture is filtered after one hour and evapo rated to a residue which is heated with stirring at 50°C. for 2 hours with a solvent mixture of 2 ml of acetic acid, and 4 ml of 0.5N sulfuric acid. The mixture is cooled and filtered followed by evaporation of the filtrate in vacuo to a residue, which is chromatographed on a suitable ion-exchange resin, in the acid form, and eluted with 2% ammonium hydroxide. The desired product is obtained as ammonium salt by evaporation of the product fractions. (dec. 212°C)

General Description

Clindamycin phosphate (Cleocin Phosphate) is the 2-phosphateester of clindamycin. It exists as a zwitterionic structurethat is very soluble in water. It is intended for parenteral(intravenous or intramuscular) administration for the treatmentof serious infections and instances when oral administrationis not feasible. Solutions of clindamycin phosphateare stable at room temperature for 16 days and for up to 32days when refrigerated.

Contact allergens

This lincosanide antibiotic is used in topical form for acne, or systemically has been responsible for exanthematous rashes and acute generalized exanthematous pustulosis.

Pharmacology

Clindamycin phosphate is available in 1% concentration in a hydroalcoholic vehicle (30 or 60 mL) as a gel or lotion. Although the drug has not been detected in the blood after topical use, its detection in the urine suggests that 4% to 5% of topically applied clindamycin is absorbed.

Structure and conformation

Semisynthetic derivative of lincomycin.

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