Bacterial protein synthesis; Antibiotic; The antibacterial target of clindamycin is the 50S subunit of the bacterial ribosome. It binds specifically to the 23S ribosomal RNA, inhibiting peptidyl transferase activity and blocking peptide chain elongation, thereby suppressing bacterial protein synthesis. This mechanism of action results in primarily bacteriostatic activity.

In vitro activity studies demonstrate that clindamycin possesses potent antibacterial effects against a wide range of anaerobes and gram-positive bacteria. Against Cutibacterium acnes, the minimum inhibitory concentration (MIC) can be as low as 0.02 μg/mL, indicating high activity. Clindamycin also exhibits good in vitro activity against pathogens associated with bacterial vaginosis, including Gardnerella vaginalis, Bacteroides spp., and Peptostreptococcus spp.. Furthermore, one study reports an IC50 of 12 nM against Plasmodium falciparum.

Adapalene 0.1% with clindamycin phosphate 1.2% (ADA + CLNP) and the fixed-dose combination of clindamycin phosphate with benzoyl peroxide 3% (CLNP/BPO 3%) are strongly recommended as first-line topical therapies for the early treatment of acne vulgaris in Japan. This phase IV, multicenter study was conducted to compare the early efficacy and safety of CLNP/BPO 3% with the Japanese standard topical regimen of ADA + CLNP. A total of 351 patients were randomized to receive either CLNP/BPO 3% or ADA + CLNP once daily for 12 weeks. The primary endpoint was the percent reduction from baseline in total lesion count at week 2. Secondary endpoints included percent changes in total, inflammatory, and non-inflammatory lesion counts; Investigator's Static Global Assessment score; quality of life assessed by Skindex-16; and patient preference. Local tolerability and adverse events were also monitored. At week 2, CLNP/BPO 3% demonstrated a significantly greater percent reduction in total lesion count compared with ADA + CLNP, and this superiority persisted through week 4. Over the 2- to 12-week period, CLNP/BPO 3% was superior in reducing inflammatory lesions, though not non-inflammatory lesions. Additionally, CLNP/BPO 3% showed greater improvements in patient quality of life and Investigator's Static Global Assessment scores, and received higher patient preference ratings. Both treatments were well tolerated; however, adverse drug reactions occurred more frequently in the ADA + CLNP group (37%) than in the CLNP/BPO 3% group (17%). In conclusion, CLNP/BPO 3% demonstrated superior early efficacy and a more favorable safety profile compared with ADA + CLNP for the treatment of acne vulgaris in Japan. [2]

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A single-center, single-arm, open-label study was conducted to evaluate the efficacy and safety of a novel thermosetting bioadhesive vaginal gel containing 2% clindamycin phosphate for the treatment of bacterial vaginosis. Thirty patients diagnosed with bacterial vaginosis based on Amsel criteria were enrolled; a subset of ten patients also underwent Nugent score assessment. Eligible participants received a single 5 g dose of 2% clindamycin phosphate vaginal gel via a prefilled applicator. Patients returned for follow-up visits 7–14 days post-dose and again 21–30 days post-dose. Two patients were excluded from the cure rate analysis. Among the 28 evaluable patients, 24 (86%) achieved clinical cure at the first follow-up visit following a single dose. Of the seven evaluable patients in the Nugent-scored subset, four (57%) achieved bacteriologic cure and four (57%) demonstrated therapeutic response. Among the 24 women who were cured at the first follow-up visit based on Amsel criteria, 23 (96%) remained cured at the final visit. In the Nugent-scored subset, seven of nine evaluable patients (78%) had a Nugent score ≤ 3 at the final visit, and six of nine (67%) were considered therapeutically cured. No adverse reactions, including local tolerability issues, were reported throughout the study. These findings support further clinical evaluation of 2% clindamycin phosphate vaginal gel for bacterial vaginosis. [3]

As the mechanism of action involves inhibition of bacterial ribosomes, cell-free assays for clindamycin typically utilize cell-free translation systems or ribosome binding assays. A standard protocol involves isolating and purifying ribosomes from target bacteria such as E. coli or S. aureus. Radiolabeled clindamycin is then incubated with the purified ribosomes in a buffer containing specific ions like Mg²⁺. After incubation, the ribosome-drug complex is separated by filtration or precipitation, and radioactivity is measured by liquid scintillation counting to determine the binding affinity.

In vitro cellular assays for clindamycin phosphate are used to evaluate its antibacterial activity against specific bacteria, typically using the broth microdilution method to determine the Minimum Inhibitory Concentration (MIC). The procedure involves culturing the target bacteria to the logarithmic phase and adjusting the suspension to a 0.5 McFarland standard. Clindamycin phosphate is then serially diluted two-fold in a 96-well plate, and the bacterial suspension is added. After incubation at 35±2°C under aerobic or anaerobic conditions for 16-24 hours, the turbidity in each well is visually inspected or read using a microplate reader to determine the MIC, defined as the lowest drug concentration that inhibits visible bacterial growth.

The investigational product was a thermosetting bioadhesive vaginal gel containing 2.0% clindamycin phosphate (expressed as the free base). The formulation consisted of Poloxamer 407, xanthan gum, citric acid, sodium citrate, and benzyl alcohol in purified water. The gel was manufactured in compliance with current Good Manufacturing Practices and filled into pre-filled vaginal applicators, each delivering a single 5.0 g dose. [3]
A single-center, open-label clinical study was conducted at OB/GYN Associates of Montgomery (Montgomery, AL, USA) to evaluate the gel's efficacy and safety in patients with bacterial vaginosis. As clindamycin phosphate is an approved active ingredient for intravaginal use, and all excipients are components of existing vaginal products, the study was exempt from Institutional Review Board approval. Written informed consent was obtained from all participants prior to enrollment. [3]
A total of 30 women, aged 17 to 51 years and self-identifying as Caucasian or African American, were enrolled. Eligibility was assessed through patient history, pelvic examination, and fulfillment of all four Amsel criteria: (1) presence of a thin, homogeneous, off-white vaginal discharge with minimal or absent pruritus and vulvovaginal inflammation; (2) vaginal pH > 4.5; (3) presence of clue cells comprising >20% of total epithelial cells on saline wet mount microscopy; and (4) a positive whiff test (fishy odor upon addition of 10% potassium hydroxide to vaginal discharge). In the last ten enrolled subjects, vaginal smears were also evaluated using the Nugent scoring system, which quantifies bacterial morphotypes on Gram-stained slides. [3]
Eligible patients received a single dose of the 2% clindamycin phosphate vaginal gel at the enrollment visit (Visit 1). Participants returned for follow-up visits approximately 7–14 days (Visit 2) and 21–30 days (Visit 3) after gel administration. At each follow-up visit, pelvic examination was repeated, and all four Amsel criteria were reassessed. Patients were also queried regarding comfort and tolerability following the initial treatment. For the subset of ten subjects, Nugent scores were re-evaluated at Visits 2 and 3.

Clindamycin phosphate is a water-soluble prodrug ester of the semisynthetic antibiotic clindamycin . It is designed for parenteral and topical/intravaginal administration, as it lacks intrinsic antibacterial activity until hydrolyzed in vivo to the active parent compound, clindamycin . The physicochemical properties that influence its disposition include a logP of 0.95, pKa of 6.78, molecular weight of 504.96 g/mol, and aqueous solubility of 3220 mg/L at pH 7 .

Absorption
Oral Administration
Clindamycin (as hydrochloride salt) is well absorbed following oral administration, with approximately 90% of a dose absorbed . Food does not impede absorption but may delay it . Absolute oral bioavailability is approximately 80% and is not affected by food consumption, although absorption is delayed . In AIDS patients, bioavailability has been reported to be higher (75%) compared to healthy volunteers (53%) .

Parenteral Administration
Following intramuscular injection of clindamycin phosphate, peak serum clindamycin concentrations (3.17–6.56 mg/L) are reached within 1.5–3 hours, with detectable levels observed after 20 minutes. Approximately 75% of the drug reaches the plasma as active clindamycin .
After intravenous infusion (300–1200 mg), peak clindamycin concentrations appear approximately 3 hours after the end of infusion, ranging from 5.4 mg/L (300 mg dose) to 15.87 mg/L (1200 mg dose) . Approximately 10% of the drug remains in serum after 8 hours as clindamycin phosphate .

Intravaginal Administration
Following intravaginal administration of clindamycin phosphate suppositories (100 mg clindamycin equivalent once daily for 3 days), approximately 30% (range 6–70%) of the administered dose is systemically absorbed based on AUC comparisons. Peak plasma concentrations (Cmax) average 0.27 µg/mL (range 0.03–0.67 µg/mL), occurring about 5 hours post-dose (range 1–10 hours). The mean AUC at steady state is 3.2 µg·hr/mL (range 0.42–11 µg·hr/mL) .

Intraperitoneal Administration
In continuous ambulatory peritoneal dialysis patients receiving 600 mg clindamycin phosphate intraperitoneally, dialysate clindamycin concentrations exceed the effective concentration (5 µg/mL) for up to 6 hours . Transfer of clindamycin is unidirectional from dialysate to plasma .

Distribution
Clindamycin is widely distributed throughout body tissues and fluids, with the notable exception of cerebrospinal fluid (even in the presence of inflamed meninges) . It crosses the placenta and appears in breast milk .
Protein Binding
Clindamycin is 90–93% bound to plasma proteins, primarily α₁-acid glycoprotein . The unbound fraction in plasma (fup) is 0.06 for clindamycin and 0.22 for clindamycin phosphate .
Cellular Accumulation
Clindamycin accumulates extensively in phagocytic cells:
- Intracellular:extracellular concentration ratio in neutrophils: 11–15
- In macrophages and monocytes: 23
- Localizes in cytoplasm and granules
Volume of Distribution
Volume of distribution at steady state following intravenous administration:
- Healthy volunteers: 0.79 ± 0.13 L/kg
- AIDS patients: 0.66 ± 0.12 L/kg


Metabolism
Clindamycin phosphate is a prodrug that undergoes rapid hydrolysis to active clindamycin. The hydrolysis half-life is dose-dependent: 1 minute for 300 mg to 3 minutes for 1200 mg doses .
Clindamycin is primarily metabolized in the liver . Seven metabolites have been described , including:
- Clindamycin sulfoxide (37% of urinary excreted compounds)
- N-demethyl clindamycin (6%)
- Clindamycin-N-demethyl sulfoxide (2%)
- Hydroxyl derivative (~15% of urinary compounds)
- Carboxyl derivative (~15% of urinary compounds)
Metabolic clearance (intrinsic hepatic CYP3A4): 2.21 µL/min/pmol P450; CYP3A5: 0.28 µL/min/pmol P450 .

Elimination
Half-Life
- Clindamycin elimination half-life: 2–3 hours in healthy adults
- Clindamycin phosphate half-life: 0.04–0.16 hours (2.4–9.6 minutes)
- Following intravaginal administration, apparent half-life averages 11 hours (range 4–35 hours), limited by absorption rate

Clearance
Plasma clearance of clindamycin: 0.18 L/h/kg (approximately 0.27 L/h/kg in healthy volunteers) . Clindamycin phosphate clearance: 0.40 L/h/kg .

Excretion
Clindamycin is eliminated primarily via the hepatobiliary route :
- Urinary excretion: 8–28% of the dose is excreted in urine as active drug and metabolites
- Approximately 27% of urinary compounds is parent clindamycin
- Clindamycin phosphate accounts for only 1–2% of the administered dose in urine
- Renal filtration rate: 0.044 L/min
- Fecal excretion: Approximately 61% of the dose is recovered in feces over 168 hours (radiolabeled studies)
- Excretion is slow and occurs over many days

443385 rat LD50 intraperitoneal 745 mg/kg Iyakuhin Kenkyu. Study of Medical Supplies., 14(484), 1983
443385 rat LD50 oral 1832 mg/kg BEHAVIORAL: SOMNOLENCE (GENERAL DEPRESSED ACTIVITY) Toxicology and Applied Pharmacology., 27(308), 1974 [PMID:4137286]
443385 rat LD50 intramuscular >3500 mg/kg Gekkan Yakuji. Pharmaceuticals Monthly., 25(691), 1983
443385 mouse LD50 intravenous 820 mg/kg Iyakuhin Kenkyu. Study of Medical Supplies., 14(484), 1983
443385 rat LD50 intravenous 321 mg/kg Iyakuhin Kenkyu. Study of Medical Supplies., 14(484), 1983

[1]. Eur J Clin Pharmacol. 2017 Feb;73(2):251-253.

[2]. J Dermatol. 2018 Aug;45(8):951-962.

[3]. Gynecol. 2020, 47(4), 516–518.

[4]. Ann Clin Microbiol Antimicrob. 2018 Oct 20;17(1):38.

Clindamycin phosphate is the phosphate form of clindamycin, a semi-synthetic chlorinated broad-spectrum antibiotic derived from the chemical modification of lincomycin. Clindamycin phosphate is used in topical preparations. See also: clindamycin (containing active ingredient); benzoyl peroxide; clindamycin phosphate (ingredient); clindamycin phosphate; retinoic acid (ingredient)... See more...

C18H34CLN2O8PS

504.95

504.146

C, 42.81; H, 6.79; Cl, 7.02; N, 5.55; O, 25.35; P, 6.13; S, 6.35

24729-96-2

Clindamycin hydrochloride;21462-39-5;Clindamycin palmitate hydrochloride;25507-04-4;Clindamycin;18323-44-9;Clindamycin phosphate hydrochloride;64023-51-4

443385

White to off-white solid powder.

1.4±0.1 g/cm3

159°C

114ºC

1.577

0.93

5

10

9

31

658

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])OP(=O)(O[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

UFUVLHLTWXBHGZ-MGZQPHGTSA-N

InChI=1S/C18H34ClN2O8PS/c1-5-6-10-7-11(21(3)8-10)17(24)20-12(9(2)19)15-13(22)14(23)16(18(28-15)31-4)29-30(25,26)27/h9-16,18,22-23H,5-8H2,1-4H3,(H,20,24)(H2,25,26,27)/t9-,10+,11-,12+,13+,14-,15+,16+,18+/m0/s1

(2R,3R,4S,5R,6R)-6-((1S,2S)-2-chloro-1-((2S,4R)-1-methyl-4-propylpyrrolidine-2-carboxamido)propyl)-4,5-dihydroxy-2-(methylthio)tetrahydro-2H-pyran-3-yl dihydrogen phosphate

Cleocin T; Clinda-Derm; Clindagel; Evoclin; U 28508; U-28508; U28508

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)

H2O : 100 mg/mL (198.04 mM)

Solubility in Formulation 1: 50 mg/mL (99.02 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication.

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