AUCIN SUSPENSION

Indications

• Bacterial infections
• Skin and soft tissue infections
• Respiratory tract infections
• Bone and joint infections
• Dental infections
• Acne vulgaris (topical use)
• Intra-abdominal infections

Dosage

Adults: Refer to BNF for specific dosing recommendations based on the type and severity of the infection. Dosage may vary

Mechanism of action

Clindamycin inhibits bacterial protein synthesis by binding to the 23S RNA of the 50S subunit of the bacterial ribosome. This binding impedes both the assembly of the ribosome and the translation process. Clindamycin acts as a structural analog of tRNA molecules, impairing peptide chain initiation and stimulating the dissociation of peptidyl-tRNA from bacterial ribosomes. Its action may be bacteriostatic or bactericidal, depending on the concentration achieved at the infection site and the susceptibility of the pathogen.

Pharmacodynamics

Clindamycin exerts its bacteriostatic effect through the inhibition of microbial protein synthesis. It has a relatively short time to maximum concentration (Tmax) and half-life, necessitating frequent dosing to maintain adequate antibiotic levels. Clindamycin is associated with the risk of Clostridium difficile-associated diarrhea (CDAD), which can range from mild diarrhea to severe colitis. This side effect is due to the disruption of normal gut flora and the overgrowth of C. difficile, leading to toxin production.

Pharmacokinetics

Clindamycin is well absorbed when taken orally, with a bioavailability of approximately 90%. It distributes widely in body tissues and fluids, including bone. The drug undergoes hepatic metabolism, primarily via cytochrome P450 enzymes, and is excreted in urine as both unchanged drug and metabolites. The elimination half-life is approximately 2 to 3 hours, and renal impairment may affect its clearance.

Contra-indications

• Hypersensitivity to clindamycin or lincomycin
• History of antibiotic-associated colitis
• Use in patients with significant gastrointestinal disorders

Adverse effects

• Diarrhea
• Nausea
• Vomiting
• Rash
• Abdominal pain
• Clostridium difficile-associated diarrhea (CDAD)
• Hepatotoxicity
• Allergic reactions

Interactions

• Clindamycin may enhance the effects of neuromuscular blocking drugs
• Clindamycin may interact with other antibiotics leading to altered susceptibility patterns

Precautions

• Use with caution in patients with renal impairment
• Monitor for signs of colitis
• Assess liver function prior to therapy
• Avoid use in patients with a history of significant gastrointestinal disease

Pregnancy

Clindamycin is classified as category B. Animal studies have not demonstrated a risk to the fetus, but there are no adequate and well-controlled studies in pregnant women.

Breast-feeding

Clindamycin is excreted in breast milk, but significant absorption by the infant is unlikely. Caution is advised.

Storage

Store in a cool, dry place away from light. Reconstituted solutions should be stored in accordance with manufacturer guidelines and used within the specified time frame.

Formulations

• Oral capsules
• Oral suspension
• Solution for injection
• Topical solution and gel

Mechanism of action

Excessive palmitoylcarnitine formation and exhausted L-carnitine stores lead to energy depletion, which, along with attenuated acetylcholine synthesis and oxidative stress, are main mechanisms behind palmitate-induced neuronal loss. High levels of palmitate exposure are suggested to contribute to diabetic neuropathy and gastrointestinal dysregulation. Additionally, palmitate negatively regulates acetyl-CoA carboxylase, thereby preventing further palmitate generation.

Pharmacodynamics

Palmitate is the first fatty acid generated during lipogenesis and serves as a precursor for the synthesis of longer fatty acids. The presence of palmitate inhibits acetyl-CoA carboxylase, reducing the conversion of acetyl-ACP to malonyl-ACP, which subsequently decreases the synthesis of new palmitate. This feedback mechanism is crucial for maintaining lipid homeostasis within the body.

Pharmacokinetics

Palmitate is absorbed from dietary sources and can also be synthesized endogenously in the liver and adipose tissue. Once in circulation, it is transported via chylomicrons or albumin. The metabolism of palmitate occurs primarily in the mitochondria through fatty acid oxidation, generating acetyl-CoA, which can enter the citric acid cycle for energy production. The overall kinetics of palmitate are influenced by dietary intake, metabolic demand, and hormonal regulation.

Pregnancy

Palmitate is classified as a category C drug. Animal reproduction studies have not been conducted, and there are no adequate and well-controlled studies in pregnant women. It should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

There are no data on the excretion of palmitate in human milk. Caution should be exercised when administering to nursing mothers.

Storage

Store at room temperature, away from light and moisture. Keep the container tightly closed.

Formulations

• Palmitate 500 mg softgel
• Palmitate 1000 mg softgel

Mechanism of action

Clindamycin inhibits bacterial protein synthesis by binding to 23S RNA of the 50S subunit of the bacterial ribosome. It impedes both the assembly of the ribosome and the translation process. The molecular mechanism through which this occurs is thought to be due to clindamycin's three-dimensional structure, which closely resembles the 3'-ends of L-Pro-Met-tRNA and deacylated-tRNA during the peptide elongation cycle - in acting as a structural analog of these tRNA molecules, clindamycin impairs peptide chain initiation and may stimulate dissociation of peptidyl-tRNA from bacterial ribosomes. The mechanism through which topical clindamycin treats acne vulgaris is unclear, but may be related to its activity against _Propionibacterium acnes_, a bacteria that has been associated with acne. Clindamycin may be bacteriostatic or bactericidal in action, depending on the concentration of the drug attained at the site of infection and the susceptibility of the infecting organism. Clindamycin palmitate hydrochloride and clindamycin phosphate are inactive until hydrolyzed to free clindamycin. This hydrolysis occurs rapidly in vivo. Clindamycin appears to inhibit protein synthesis in susceptible organisms by binding to 50S ribosomal subunits; the primary effect is inhibition of peptide bond formation. The site of action appears to be the same as that of erythromycin, chloramphenicol, and lincomycin. Clindamycin binds exclusively to the 50S subunit of bacterial ribosomes and suppresses protein synthesis. ... Clindamycin is not a substrate for macrolide efflux pumps, and strains that are resistant to macrolides by this mechanism are susceptible to clindamycin.

Pharmacodynamics

Clindamycin exerts its bacteriostatic effect via inhibition of microbial protein synthesis. Clindamycin has a relatively short T_max and half-life necessitating administration every six hours to ensure adequate antibiotic concentrations. _Clostridium difficile_ associated diarrhea (CDAD) has been observed in patients using clindamycin, ranging in severity from mild diarrhea to fatal colitis and occasionally occurring over two months following cessation of antibiotic therapy. Overgrowth of _C. difficile_ resulting from antibiotic use, along with its production of A and B toxins, contributes to morbidity and mortality in these patients. Because of the associated risks, clindamycin should be reserved for serious infections for which the use of less toxic antimicrobial agents are inappropriate. Clindamycin is active against a number of gram-positive aerobic bacteria, as well as both gram-positive and gram-negative anaerobes. Resistance to clindamycin may develop, and is generally the result of base modification within the 23S ribosomal RNA. Cross-resistance between clindamycin and lincomycin is complete, and may also occur between clindamycin and macrolide antibiotics (e.g. [erythromycin]) due to similarities in their binding sites. As antimicrobial susceptibility patterns are geographically distinct, local antibiograms should be consulted to ensure adequate coverage of relevant pathogens prior to use.

Mechanism of action

... Excessive palmitoylcarnitine formation and exhausted L-carnitine stores leading to energy depletion, attenuated acetylcholine synthesis and oxidative stress to be main mechanisms behind PA-induced neuronal loss.High PA exposure is suggested to be a factor in causing diabetic neuropathy and gastrointestinal dysregulation. ... First phase insulin release response was lost in these islets. FFAs slightly increased the insulin output of normal fresh pancreas beta-cells. However, chronic exposure to FFAs resulted in loss of first phase insulin release and blunted insulin secretion response to various levels of D-glucose stimulation.

Pharmacodynamics

Palmitic acid is the first fatty acid produced during lipogenesis (fatty acid synthesis) and from which longer fatty acids can be produced. Palmitate negatively feeds back on acetyl-CoA carboxylase (ACC) which is responsible for converting acetyl-ACP to malonyl-ACP on the growing acyl chain, thus preventing further palmitate generation