In ATCC 25923 and E19977, the dicloxacillin EC50 values are 0.06 and 0.50 mg/L, respectively. At pH 7.4, the minimum inhibitory concentrations of dicloxacillin in ATCC 25923 and E19977 are 0.125 and 0.5 mg/L, respectively [2].

In a mouse model of peritonitis sepsis, dicloxacillin had therapeutic efficacy, and all of the mice made it through [3].

Animal/Disease Models: Female outbred Swiss Webster mice (murine peritonitis sepsis model) [3].
Doses: 125 mg/kg. Mode of
Route of Administration: intravenous (iv) (iv)injection, single dose.
Experimental Results: All mice survived.

Absorption, Distribution and Excretion
Isoxazolidin is rapidly but incompletely absorbed orally: peak plasma concentrations are reached within 1–1.5 hours. Oral absorption is delayed when taken after meals with cloxacillin, dicloxacillin, oxazolicillin, and nafcillin. Dicloxacillin sodium is rapidly excreted in the urine primarily as the unchanged drug via glomerular filtration and active tubular secretion. Differences in elimination, distribution, and absorption of dicloxacillin and cloxacillin were investigated in a cohort of healthy individuals using a two-compartment model. In patients undergoing chronic intermittent hemodialysis, only dicloxacillin was studied, and results were compared with previous studies on cloxacillin and flucloxacillin. In healthy volunteers, the bioavailability of 2 g of dicloxacillin or 2 g of cloxacillin, calculated based on the area under the serum concentration-time curve, was 48.8% and 36.9% of the dose, respectively; the bioavailability based on urinary excretion was 74.1% and 48.5%, respectively. Following oral administration, the bioavailability of dicloxacillin showed slightly lower inter-individual variability than that of cloxacillin. The higher serum concentrations of dicloxacillin compared to cloxacillin are also attributed to its slower (renal) clearance (half-lives of 42 min and 33 min, respectively). Serum concentration analyses following intravenous administration of 1 g and 2 g of dicloxacillin in healthy subjects showed concentration-dependent renal clearance kinetics. In hemodialysis patients, the elimination rate of dicloxacillin (half-life: 129 min) was consistent with the extrarenal elimination rate in healthy subjects. The bioavailability of 1 g of dicloxacillin after oral administration was good (75.9% of the dose). Dicloxacillin is a semi-synthetic isoxazolylpenicillin antibiotic with antibacterial activity against a variety of Gram-positive bacteria, including Staphylococcus aureus, Streptococcus pyogenes, Streptococcus pneumoniae, Streptococcus epidermidis, Streptococcus viridans, Streptococcus agalactiae, and Neisseria meningitidis. This study aimed to evaluate the safety and pharmacokinetic characteristics of dicloxacillin after single and multiple oral doses in healthy Chinese volunteers. This was a single-center, open-label, randomized, two-stage study that included 16 participants. In the single-dose phase, participants were randomly assigned to receive a single dose of 0.25, 0.5, 1.0, or 2.0 g dicloxacillin sodium capsules in a four-period crossover design with a 5-day washout period between doses. In the multiple-dose phase, participants were randomly assigned to receive a dose of 0.25 or 0.5 g every 6 hours for 3 days in a two-period crossover design. Validated high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) was used to analyze plasma and urinary pharmacokinetic samples. Pharmacokinetic parameters were calculated and statistically analyzed. Safety assessments were conducted throughout the study. Following single oral doses of 0.25–2.0 g dicloxacillin sodium, the maximum plasma drug concentration (Cmax) and the area under the concentration-time curve (AUC0–10 hr) increased proportionally to the dose. The mean elimination half-life (t1/2) is 1.38–1.71 hours. Dicloxacillin is excreted unchanged via the kidneys without accumulation, with excretion rates ranging from 38.65% to 50.10%. No significant drug accumulation was observed after multiple oral doses of dicloxacillin. No serious adverse events were reported. Adverse events were generally mild. Dicloxacillin is safe and well-tolerated in volunteers, with Cmax and AUC0–10 hr values increasing linearly.
The purpose of antibiotic treatment in pregnant women is to treat the mother and/or fetus, as it is known that antibiotics taken by the mother can cross the placenta to reach the fetus. Comparing drug concentrations in maternal and fetal plasma can indicate fetal exposure to antibiotics used by the mother. This study aimed to review the literature on antibiotic transport in the human placenta and to classify antibiotics according to transport type… Three types of placental transport were identified in this study. A few antibiotics can rapidly cross the placenta and reach equilibrium in maternal and umbilical cord plasma; this type of transport is called "complete transport," and includes ampicillin, methicillin, cefmeroxum, and cefotaxime. Other antibiotics cannot be completely transported to the placenta, and their concentration in umbilical cord plasma is lower than in maternal plasma; these are called "incomplete transport," and include azlocillin, dicloxacillin, piperacillin, subecillin, cefoxitin, amikacin, gentamicin, kanamycin, streptomycin, fosfomycin, thiamphenicol, griseofulvin, vancomycin, and colistin mesylate. All tested antibiotics can cross the human placenta, including antibiotics with a molecular weight greater than 1000 kDa, such as vancomycin and colistin mesylate. However, placental transport is classified into three types: complete transport, incomplete transport, and supertransport, with most antibiotics belonging to the incomplete transport category. This study aimed to determine whether the upregulation of P-glycoprotein is the cause of increased renal clearance in patients with cystic fibrosis… This study included 11 patients with cystic fibrosis and 11 age-matched healthy volunteers. All subjects received a single oral dose of dicloxacillin 500 mg, dicloxacillin 500 mg combined with probenecid (an organic anion transport inhibitor) 1 g, or dicloxacillin 500 mg combined with cyclosporine (a P-glycoprotein inhibitor) 5 mg/kg; each dose was administered 48 hours apart with a washout period. On each study day, subjects received a bolus dose of 456 mg of iotalamate meglumine as a marker of glomerular filtration rate. Blood and urine samples were collected continuously for up to 6 hours after each dose. Pharmacokinetics of dicloxacillin and iotalamate were determined using both atrioventricular and non-atrioventricular models. Quantitative polymerase chain reaction (qPCR) was performed on peripheral blood mononuclear cells to detect the expression of multidrug resistance gene 1 (MDR1) messenger RNA (mRNA). ABCB1 genotyping was performed to determine the presence of single nucleotide polymorphisms (exons 21 and 26). In healthy subjects and patients with cystic fibrosis, combination therapy with probenecid significantly reduced dicloxacillin renal clearance compared to dicloxacillin alone, while combination therapy with cyclosporine did not result in a significant change; there was no significant difference in renal clearance between the two groups. No correlation was found between MDR1 mRNA expression and dicloxacillin renal clearance. Compared to subjects with the CT genotype, subjects with the ABCB1 exon 26 TT polymorphism showed a significantly increased renal excretion of dicloxacillin. There was no significant difference in the pharmacokinetics of dicloxacillin between patients with cystic fibrosis and healthy volunteers. The renal clearance of dicloxacillin was significantly reduced in the presence of probenecid, but not in the presence of cyclosporine, suggesting that the rate-limiting step in dicloxacillin renal tubular secretion is organic anion transporter-mediated uptake, rather than P-glycoprotein inhibition. For more complete data on absorption, distribution, and excretion of dicloxacillin (22 items total), please visit the HSDB record page.

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Metabolism/Metabolites
Dicloxacillin is partially metabolized into active and inactive metabolites. In one study, following a single oral dose of 500 mg dicloxacillin, 10% of the absorbed drug was hydrolyzed to microbiologically inactive penicillic acid. Dicloxacillin also undergoes minor hydroxylation to form a microbiologically active metabolite, which appears to be slightly less active than dicloxacillin itself.

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Biological Half-Life
The elimination half-life of dicloxacillin is approximately 0.7 hours.
...In hemodialysis patients, the elimination rate of dicloxacillin (T_1/2: 129 minutes) was consistent with the extrarenal elimination rate in healthy subjects...
...Following a single oral dose of 0.25-2.0 g of dicloxacillin sodium, the maximum plasma drug concentration (C_max) and the area under the concentration-time curve (AUC_{0-10 hr}) both increased proportionally to the dose. The mean elimination half-life (t_1/2) was 1.38-1.71 hours...
The half-life of dicloxacillin in the serum of adults with normal renal function is 0.6-0.8 hours. A study in children aged 2-16 years showed that the mean serum half-life of the drug was 1.9 hours.
The half-life of dicloxacillin in the serum of patients with impaired renal function is slightly prolonged; it has been reported that the serum half-life in patients with severe renal impairment is 1-2.2 hours.

Hepatotoxicity
No serum enzyme elevations were observed during dicloxacillin treatment, but it was associated with rare, clinically significant cholestatic hepatitis. The typical onset time is 1 to 6 weeks, and the serum enzyme elevation pattern is usually cholestatic, but mixed-type cases have also been reported (Case 1). Liver injury typically presents as jaundice and pruritus. Fever, rash, and eosinophilia may also occur, but are less pronounced, and autoantibodies are rarely detected. Flucloxacillin (also known as fluoxacillin) and cloxacillin (two oral isoxazolidinyl penicillins with similar structure and activity to dicloxacillin, but never approved for use or marketing in the United States) also more frequently cause similar liver injury. Similar cholestatic hepatitis usually occurs within 1 to 6 weeks of starting treatment, and this can also occur with other penicillin classes. Probability Score: B (Very likely but rare, a cause of clinically significant liver injury).

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Effects during pregnancy and lactation
◉ Overview of medication use during lactation
Limited information suggests that dicloxacillin concentrations in breast milk are very low and are not expected to have adverse effects on breastfed infants. It is commonly used to treat mastitis in breastfeeding women. There are reports that penicillin-type drugs occasionally disrupt the infant's gut microbiota, leading to diarrhea or thrush, but these effects have not been fully assessed. Dicloxacillin can be used in breastfeeding women.
◉ Effects on breastfed infants
No relevant published information was found as of the revision date.
◉ Effects on lactation and breast milk
No relevant published information was found as of the revision date.

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Protein binding
Bindes with serum proteins, primarily albumin.

[1]. In vitro activity effects of combinations of cephalothin, dicloxacillin, imipenem, vancomycin and amikacin against methicillin-resistant Staphylococcus spp. strains. Ann Clin Microbiol Antimicrob. 2006 Oct 12;5:25.

[2]. Intra- and extracellular activities of dicloxacillin against Staphylococcus aureus in vivo and in vitro. Antimicrob Agents Chemother. 2010 Jun;54(6):2391-400.

[3]. Discovery of MRSA active antibiotics using primary sequence from the human microbiome. Nat Chem Biol. 2016 Dec;12(12):1004-1006.

Dicloxacillin is a penicillin antibiotic with the structure 6-aminopenicillanic acid, where one amino hydrogen atom is replaced by a 3-(2,6-dichlorophenyl)-5-methyl-1,2-oxazol-4-yl]formyl group. It is an antibacterial drug. It is a penicillin compound and also a dichlorobenzene compound. It is the conjugate acid of dicloxacillin (1-). It is one of the penicillin antibiotics resistant to penicillinase. Dicloxacillin is a penicillin antibiotic. Dicloxacillin is an oral second-generation penicillin antibiotic used to treat bacterial infections caused by penicillinase-resistant Staphylococcus aureus. Dicloxacillin has been associated with rare, clinically significant cases of specific liver injury. The effects of dicloxacillin in bovine (Bos taurus) have been reported, and relevant data are available. Dicloxacillin is a broad-spectrum, semi-synthetic β-lactam penicillin antibiotic with bactericidal and anti-β-lactamase activity. Dicloxacillin binds to penicillin-binding proteins (PBPs) located on the inner membrane of bacterial cell walls. It also inhibits the cross-linking of peptidoglycan (an important component of the bacterial cell wall). This leads to the inhibition of bacterial cell wall synthesis, ultimately resulting in cell lysis.
A penicillin antibiotic resistant to penicillinase.

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Indications
For the treatment of infections caused by penicillinase-producing Staphylococcus aureus sensitive to this drug.

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Mechanism of Action
Dicloxacillin exerts its bactericidal effect on penicillin-sensitive microorganisms during the active reproductive phase of bacteria. All penicillin antibiotics inhibit bacterial cell wall biosynthesis. Dicloxacillin inhibits the third and final stage of bacterial cell wall synthesis by binding to specific penicillin-binding proteins (PBPs) located within the bacterial cell wall. Cell lysis is subsequently mediated by bacterial cell wall autolysins, such as autolysins; dicloxacillin may interfere with the action of autolysin inhibitors.

C19H17CL2N3O5S

470.33

469.026

3116-76-5

Dicloxacillin Sodium hydrate;13412-64-1;Dicloxacillin-13C4

18381

Typically exists as solid at room temperature

1.6±0.1 g/cm3

692.4±55.0 °C at 760 mmHg

372.5±31.5 °C

0.0±2.3 mmHg at 25°C

1.691

3.02

2

7

4

30

746

3

CC1=C(C(N[C@@H]2C(N3[C@H](C(C)(S[C@H]23)C)C(O)=O)=O)=O)C(C4=C(Cl)C=CC=C4Cl)=NO1

YFAGHNZHGGCZAX-JKIFEVAISA-N

InChI=1S/C19H17Cl2N3O5S/c1-7-10(12(23-29-7)11-8(20)5-4-6-9(11)21)15(25)22-13-16(26)24-14(18(27)28)19(2,3)30-17(13)24/h4-6,13-14,17H,1-3H3,(H,22,25)(H,27,28)/t13-,14+,17-/m1/s1

(2S,5R,6R)-6-[[3-(2,6-dichlorophenyl)-5-methyl-1,2-oxazole-4-carbonyl]amino]-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid

Dicloxacilline Dicloxacilina Dicloxacillin

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.)