Absorption, Distribution and Excretion
Clarithromycin is well absorbed, acid-resistant, and can be taken with food. After taking a 250 mg tablet every 12 hours, approximately 20% of the dose is excreted in the urine as clarithromycin; after taking a 500 mg tablet every 12 hours, the urinary excretion of clarithromycin is slightly higher, approximately 30%. Limited data are available on the distribution of clarithromycin in the human body. Clarithromycin and 14-hydroxyclarithromycin appear to be distributed in most body tissues and fluids. Due to higher intracellular concentrations, tissue concentrations are higher than serum concentrations. High concentrations of clarithromycin have been detected in tissue samples from patients who have undergone surgery. Reports indicate that patients who received 250-500 mg of clarithromycin orally every 12 hours for 3 days prior to surgery reached peak clarithromycin concentrations in the lungs, tonsils, and nasal mucosa 4 hours after administration, with average concentrations of 13.5-17.5, 5.3-6.5, and 5.9-8.3 mg/kg, respectively. However, studies suggest that these data may overestimate tissue concentrations of clarithromycin because microbial assays cannot distinguish between the parent drug and its active metabolites. In children receiving clarithromycin suspension for otitis media at a dose of 7.5 mg/kg every 12 hours for 5 doses, peak concentrations of clarithromycin and 14-hydroxyclarithromycin in the middle ear effusion were 2.5 and 1.3 μg/mL, respectively. Concomitant serum concentrations were 1.7 and 0.8 μg/mL, respectively. Animal studies have shown that administration of radiolabeled clarithromycin or erythromycin resulted in higher and more sustained activity of clarithromycin in various body tissues, particularly the lungs.
Clarithromycin is rapidly absorbed in the gastrointestinal tract after oral administration; its gastrointestinal absorption rate is higher than that of erythromycin.
Clarithromycin is eliminated via renal and non-renal routes.
In healthy men, after a single oral dose of 250 mg of radiolabeled clarithromycin, approximately 38% of the dose (18% of which is clarithromycin) is excreted in the urine within 5 days, and 40% of the dose (4% of which is clarithromycin) is excreted in the feces. With oral clarithromycin tablets, taken at 250 or 500 mg every 12 hours, approximately 20% or 30% of the dose is excreted unchanged in the urine within 12 hours. With oral clarithromycin suspension, taken at 250 mg every 12 hours, approximately 40% of the administered dose is excreted unchanged in the urine. The major metabolite of clarithromycin is 14-hydroxyclarithromycin, which accounts for approximately 10-15% of the dose after taking 250 or 500 mg of clarithromycin tablets in the urine. For more complete data on the absorption, distribution, and excretion of clarithromycins (6 in total), please visit the HSDB record page. Metabolism/Metabolites Hepatic Metabolism - Primarily metabolized by CYP3A4, leading to various drug interactions. The major metabolite of clarithromycin is 14-hydroxyclarithromycin, which accounts for approximately 10-15% of the dose in urine after administration of 250 or 500 mg clarithromycin tablets. Clarithromycin is extensively metabolized in the liver, primarily through oxidative N-demethylation and 14-hydroxylation; the glycosyl moiety of clarithromycin is also subject to minor hydrolysis in the stomach. Although at least 7 clarithromycin metabolites have been identified, 14-hydroxyclarithromycin is the major serum metabolite and the only one with significant antibacterial activity. Both the R- and S-epimers of 14-hydroxyclarithromycin can be generated in vivo, but the R-epimer is more abundant and exhibits stronger antibacterial activity. Clarithromycin metabolism appears to be saturated, as the amount of 14-hydroxyclarithromycin produced after taking 800 mg of the parent drug is only slightly higher than that produced after taking 250 mg of the parent drug. Following a single oral dose of 250 mg of radiolabeled clarithromycin in healthy men, approximately 38% of the dose (18% clarithromycin) is excreted in the urine within 5 days, and 40% (4% clarithromycin) is excreted in the feces. The major metabolite found in the urine is 14-hydroxyclarithromycin, accounting for approximately 10-15% of the dose after taking 250 or 500 mg clarithromycin tablets. Biological Half-Life: 3-4 hours. Following a single oral dose of 250 mg or 1.2 g of a standard clarithromycin tablet in healthy men, the average elimination half-life is 4 hours and 11 hours, respectively. Reports indicate that when clarithromycin is administered multiple times every 12 hours, the elimination half-life increases from 3–4 hours after taking 250 mg (conventional tablets) every 12 hours to 5–7 hours after taking 500 mg every 8–12 hours; the half-life of 14-hydroxyclarithromycin increases from 5–6 hours at a 250 mg dose to 7–9 hours at a 500 mg dose. When clarithromycin is administered as an oral suspension, the elimination half-life of the drug and its 14-hydroxy metabolite appears to be similar to the half-life observed upon reaching steady state after taking an equivalent dose of clarithromycin tablets.

Interactions
The manufacturer of dafinarax states that for patients concurrently taking potent CYP3A4 inhibitors (including clarithromycin), the daily dose of dafinarax should not exceed 7.5 mg. Clarithromycin and cisapride are contraindicated. Concomitant use of clarithromycin and/or erythromycin with cisapride has been associated with QT interval prolongation and serious arrhythmias (ventricular tachycardia, ventricular fibrillation, torsades de pointes); deaths have been reported. In two patients with chronic renal failure treated with cisapride (10 mg, 3-4 times daily), QT interval prolongation and/or torsades de pointes occurred within days of initiating clarithromycin (500 mg, twice daily). In one patient, serum cisapride levels were elevated; these levels decreased after discontinuation of clarithromycin.
Patients taking carbamazepine should use clarithromycin with caution; if taking both clarithromycin and carbamazepine concurrently, it is recommended to reduce the carbamazepine dose and/or monitor plasma carbamazepine concentrations. Limited data in healthy men suggest that clarithromycin may increase the area under the serum concentration-time curve (AUC) of carbamazepine and decrease the peak serum concentration and AUC of carbamazepine 10,11-epoxide (CBZ-E). Furthermore, in some patients receiving carbamazepine (600 mg/day), regardless of concomitant use with other drugs, plasma concentrations of carbamazepine (but not CBZ-E) increased within 3–5 days after initiation of clarithromycin treatment (200 mg twice daily), and in some patients, signs of carbamazepine toxicity (i.e., drowsiness, dizziness, ataxia) occurred. Plasma carbamazepine concentrations decreased upon discontinuation of carbamazepine, and toxic symptoms subsided within a few days.
The manufacturer of eszopiclone states that if eszopiclone is used concomitantly with potent CYP3A4 inhibitors (including clarithromycin), the dose of eszopiclone should be reduced. In this case, the initial dose of eszopiclone should not exceed 1 mg, but may be increased to 2 mg if clinically necessary. ⁴⁵⁷>
For more complete data on interactions of clarithromycin (36 in total), please visit the HSDB record page.

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Non-human toxicity values
Rat subcutaneous LD50 >5 g/kg
Rat intraperitoneal LD50 669 mg/kg
Rat oral LD50 1270 mg/kg
Mouse intravenous LD50 173 mg/kg
For more complete data on non-human toxicity values of clarithromycin (7 in total), please visit the HSDB record page.

Therapeutic Uses

Antimicrobial Drugs
Oral clarithromycin is often used in combination with amoxicillin and lansoprazole or omeprazole (triple therapy) to treat Helicobacter pylori infection and duodenal ulcers. Clarithromycin can also be used in combination with omeprazole (dual therapy) or bismuth citrate ranitidine to treat Helicobacter pylori infection in patients with active duodenal ulcers. In addition, clarithromycin has been used in combination with other drugs (with or without amoxicillin, lansoprazole, omeprazole, or bismuth citrate ranitidine) to treat Helicobacter pylori infection associated with peptic ulcers. /US Product Label Includes/
Oral clarithromycin is used to treat pharyngitis and tonsillitis, mild to moderate respiratory infections (acute bacterial exacerbation of chronic bronchitis, acute maxillary sinusitis, community-acquired pneumonia), uncomplicated skin and soft tissue infections, and acute otitis media caused by susceptible bacteria. Clarithromycin is also used orally to treat disseminated infection with Mycobacterium avium complex (MAC) in patients with advanced human immunodeficiency virus (HIV) infection, and to prevent disseminated MAC infection in HIV-infected individuals (primary and secondary prevention). /Included on US product label/
Clarithromycin (regular tablets) is used in combination with amoxicillin and lansoprazole or omeprazole (triple therapy) to treat patients with active or less than 1-year history of duodenal ulcers caused by Helicobacter pylori (formerly known as Campylobacter pylori or H. pylori) infection. Clarithromycin may also be used in combination with omeprazole (dual therapy) or bismuth citrate ranitidine to treat H. pylori infection in patients with active duodenal ulcers. /Included on US product label/
For more complete data on the therapeutic uses of clarithromycin (out of 17), please visit the HSDB record page.

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Drug Warnings
38 cases of neurotoxicity caused by clarithromycin have been reported. The mean age of the patients was 51.3 years (range: 19–87 years), with 52.6% being female. Mental illness was the most common comorbidity, with only two patients experiencing renal failure. Most patients were taking clarithromycin to treat respiratory infections, with only two patients taking more than 1000 mg of antibiotics daily. Symptoms appeared within 1 to 10 days after starting clarithromycin (mean 5 days). 71% of patients were taking other medications concurrently, with 8 patients receiving psychoactive drugs. Patient prognosis was good after discontinuation of clarithromycin, but 58% required antipsychotics or benzodiazepines during the acute phase. Only 4 patients underwent electroencephalography (EEG). A typical patient in our case was a 74-year-old woman who developed delirium due to clarithromycin-induced nonconvulsive status epilepticus (NCSE). Her clinical symptoms and EEG results significantly improved after discontinuation of clarithromycin. The underlying mechanisms of central nervous system side effects are unclear. We recommend incorporating electroencephalography (EEG) into the diagnostic process for patients exhibiting neurotoxic symptoms during clarithromycin treatment, as EEG helps differentiate patients with mental illness from those with encephalopathy or epilepsy. Due to the widespread use of clarithromycin, clinicians should be fully aware of its neurotoxicity. Early detection and discontinuation of clarithromycin-induced neurotoxicity may lead to complete recovery. Researchers treated 13 elderly patients with chronic mycobacterial lung disease with clarithromycin monotherapy at a dose of 1000 mg twice daily. The mean age of the patients was 70 years, and 12 of the 13 patients had creatinine clearance of 31–71 ml/min. Adverse reactions occurred in all patients; the most common adverse reactions were bitterness (92%), nausea (92%), vomiting (54%), and central nervous system symptoms (54%). Elevated liver enzymes occurred in 5 of the 13 patients (38%) within 1–6 weeks of treatment. The mean serum concentration of clarithromycin and its 14-OH metabolite was 12.9 ± 3.6 μg/ml (standard deviation). Eleven patients (85%) discontinued high-dose medication within 3 months due to side effects. In the six patients who discontinued, serum drug concentrations of clarithromycin and its 14-OH metabolite consistently exceeded 12 μg/mL in all six (10/10); however, in the two patients who tolerated the high dose, this concentration was not reached in either (0/6). Reducing the dose to 500 mg twice daily was well tolerated (9 out of 10 patients tolerated it). Future trials of clarithromycin in this population should use lower doses, with close monitoring of body weight and renal function to minimize side effects. In animal studies, corneal opacity occurred at doses of 8–12 times the maximum recommended human dose (mg/m²). Other adverse reactions reported with clarithromycin in combination with omeprazole differed from those with omeprazole alone, including rhinitis (2% of patients), pharyngitis (1% of patients), and flu-like symptoms (1% of patients).
For more complete (22) drug warnings about clarithromycin, please visit the HSDB record page.

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Pharmacodynamics
Clarithromycin is a macrolide antibiotic with an antibacterial spectrum that includes a wide range of Gram-positive bacteria (Staphylococcus aureus, Streptococcus pneumoniae, and Streptococcus pyogenes) and is effective against Gram-negative aerobic bacteria (such as Haemophilus influenzae, Haemophilus parainfluenzae, and Moraxella catarrhalis), a wide range of anaerobes, some mycobacteria, and other microorganisms (including Mycoplasma, Ureaplasma, Chlamydia, Toxoplasma gondii, and Borrelia burgdorferi). Clarithromycin also has antibacterial activity against aerobic bacteria such as Chlamydia pneumoniae and Mycoplasma pneumoniae. In vitro studies have shown that clarithromycin has comparable or stronger antibacterial activity against erythromycin-sensitive bacteria. Clarithromycin is usually a bacteriostatic agent, but depending on the microbial species and drug concentration, it may also have bactericidal activity.

747.477

116836-41-0

84029

Colorless needles from chloroform + diisopropyl ether (1:2) ... Also reported as crystals from ethanol

2.439

4

14

8

52

1190

18

AGOYDEPGAOXOCK-KCBOHYOISA-N

InChI=1S/C38H69NO13/c1-15-26-38(10,45)31(42)21(4)28(40)19(2)17-37(9,47-14)33(52-35-29(41)25(39(11)12)16-20(3)48-35)22(5)30(23(6)34(44)50-26)51-27-18-36(8,46-13)32(43)24(7)49-27/h19-27,29-33,35,41-43,45H,15-18H2,1-14H3/t19-,20-,21+,22+,23-,24+,25+,26-,27+,29-,30+,31-,32+,33-,35+,36-,37-,38-/m1/s1

(3R,4S,5S,6R,7R,9R,11R,12R,13S,14R)-6-[(2S,3R,4S,6R)-4-(dimethylamino)-3-hydroxy-6-methyloxan-2-yl]oxy-14-ethyl-12,13-dihydroxy-4-[(2R,4R,5S,6S)-5-hydroxy-4-methoxy-4,6-dimethyloxan-2-yl]oxy-7-methoxy-3,5,7,9,11,13-hexamethyl-oxacyclotetradecane-2,10-dione

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.)