Absorption, Distribution and Excretion
Spiramycin is not completely absorbed. Oral bioavailability is 30-39%. Spiramycin is absorbed more slowly than erythromycin. Its pKa value is high (7.9), likely due to its high ionization in the acidic environment of the stomach. The fecal-biliary route is the primary route of excretion. The secondary route is the renal-urinary route. Spiramycin has a wide tissue distribution. Its volume of distribution exceeds 300 liters, and its concentrations in bones, muscles, respiratory tract, and saliva are higher than in serum. Spiramycin reaches higher concentrations in tissues such as the lungs, bronchi, tonsils, and sinuses. 80% of the administered dose is excreted via bile, making the fecal-biliary route the most important. Enterohepatic circulation may also occur. Only 4% to 14% of the administered dose is cleared via the renal-urinary route. Spiramycin is well absorbed in the human body after oral administration. In healthy young adult males, after oral administration of 15-30 mg/kg body weight, peak plasma concentrations are reached within 3-4 hours, with plasma concentrations ranging from 0.96-1.65 mg/L. Following intravenous administration (7.25 mg/kg body weight), a larger volume of distribution (Vdss 5.6 L/kg) was observed, indicating extensive tissue distribution. Biotransformation appears to be unimportant. Bile excretion is the primary route of excretion; only 7-20% of the oral dose is excreted in the urine. Spiramycin is known to achieve high tissue/serum concentration ratios in lung, prostate, and skin tissues. Spiramycin can cross the placenta and enter the fetus. After daily administration of 2 g of the antibiotic, the concentrations in maternal serum, umbilical cord blood, and placenta were 1.19 μg/mL, 0.63 μg/mL, and 2.75 μg/mL, respectively. When the maternal dose was increased to 3 g daily, these concentrations were 1.69 μg/mL, 0.78 μg/mL, and 6.2 μg/mL, respectively. Based on these results, the concentration ratio of umbilical cord blood to maternal serum was approximately 0.5. Furthermore, at these doses, the concentration of spiramycin in the placenta was approximately 2-4 times that in maternal serum. ...Spiramycin is secreted into milk. Infants nursed by mothers who received 1.5 g of spiramycin daily for three consecutive days had a serum spiramycin concentration of 20 μg/mL. This concentration exhibits antibacterial activity. Spiramycin is a macrolide antibiotic effective against most microorganisms isolated from the milk of mastitis-affected cows. This study investigated the distribution of spiramycin in plasma and milk after intravenous, intramuscular, and subcutaneous injections. Twelve healthy dairy cows were single-dose spiramycin injections at doses of 30,000 IU/kg via the three routes described above. Plasma and milk samples were collected after injection. The concentration of spiramycin in plasma was determined by high-performance liquid chromatography (HPLC), and the concentration of spiramycin in milk was determined using microbiological methods. Following intravenous administration, the mean residence time of spiramycin in breast milk (20.7 ± 2.7 h) was significantly longer than that in plasma (4.0 ± 1.6 h) (P < 0.01). The mean breast milk/plasma concentration ratio was calculated to be 36.5 ± 15 based on the area under the concentration-time curve. To determine the bioequivalence of the two extravascular administration routes, several pharmacokinetic parameters were investigated. Intramuscular or subcutaneous administration resulted in nearly 100% absorption, demonstrating bioequivalence to the extravascular route, although significant differences were observed in absorption rate, maximum plasma concentration, and time to peak concentration between the two routes. There was no difference in spiramycin excretion in breast milk between the two extravascular routes, but the latter was not bioequivalent in terms of maximum plasma concentration in breast milk. However, the two routes were bioequivalent for the duration during which spiramycin concentrations in breast milk exceeded the minimum inhibitory concentration (MIC) for various pathogens causing breast infections. Plasma protein binding ranged from 10% to 25%. Following oral administration of 6 million units, peak plasma concentration was 3.3 μg/mL 1.5 to 3 hours later; the half-life was approximately 5 to 8 hours. Even when plasma concentrations decreased to low levels, tissue concentrations remained high. For more complete data on the absorption, distribution, and excretion of spiramycin (13 in total), please visit the HSDB record page.
Metabolism/Metabolites
Spiramycin is metabolized less readily than some other macrolide antibiotics. Its metabolic processes have not been fully studied. It is primarily metabolized in the liver to its active metabolite. In cattle, a metabolite called neospiramycin, a norcarboxylic acid derivative, is produced. 14–28 days after administration, neospiramycin concentrations in muscle and kidneys were slightly higher than spiramycin; the concentrations of neospiramycin and spiramycin in muscle were approximately equal. Spiramycin is metabolized in the liver to its active metabolite; most is excreted via bile, and approximately 10% is excreted via urine.

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Biological Half-Life
Intravenous injection: Young adults (18 to 32 years): Approximately 4.5 to 6.2 hours. Older adults (73 to 85 years): Approximately 9.8 to 13.5 hours. Oral administration: 5.5 to 8 hours; Rectal administration in children: 8 hours.
The half-life of a 6 million oral dose is approximately 5 to 8 hours.

Protein Binding

Low protein binding levels (10-25%).

[1]. Hydroxylation and hydrolysis: two main metabolic ways of spiramycin I in anaerobic digestion. Bioresour Technol. 2014 Feb;153:95-100.

Spiramycin is a macrolide antibiotic primarily acting as an inhibitor, active against Gram-positive cocci and bacilli, Gram-negative cocci, Legionella, Mycoplasma, Chlamydia, certain types of spirochetes, Toxoplasma gondii, and Cryptosporidium. Spiramycin is a 16-membered ring macrolide compound, first discovered in Streptomyces ambofaciens in 1952. Oral formulations have been available since 1955, and injectable formulations since 1987. Resistant bacteria include Enterobacteriaceae, Pseudomonas, and fungi. Spiramycin is a macrolide compound, initially discovered in Streptomyces ambofaciens, possessing antibacterial and antiparasitic activity. Although its specific mechanism of action is not fully elucidated, spiramycin may inhibit protein synthesis by binding to the 50S subunit of bacterial ribosomes. This drug can also prevent placental transmission of toxoplasmosis, the mechanism of which may differ from previous methods, but this is not yet clear. Drug Indications Macrolide antibiotics are used to treat various infections. Mechanism of Action The mechanism of action of macrolide antibiotics remains controversial. Spiramycin is a 16-membered ring macrolide antibiotic that binds to the bacterial 50S ribosomal subunit in a 1:1 stoichiometric ratio, thereby inhibiting ribosome translocation. This antibiotic effectively inhibits the binding of both donor and acceptor substrates to the ribosome. Its primary mechanism of action is through promoting the dissociation of peptidyl-tRNA from the ribosome during ribosome translocation.

C43H74N2O14

843.052660000001

842.514

24916-50-5

5289394

Off-white to light yellow solid powder

1.21g/cm3

913.7ºC at 760mmHg

134-137ºC

506.4ºC

2.325

4

16

11

59

1370

19

C[C@@H]1C/C=C/C=C/[C@@H]([C@@H](C[C@@H]([C@@H]([C@H]([C@@H](CC(=O)O1)O)OC)O[C@H]2[C@@H]([C@H]([C@@H]([C@H](O2)C)O[C@H]3C[C@@]([C@H]([C@@H](O3)C)O)(C)O)N(C)C)O)CC=O)C)O[C@H]4CC[C@@H]([C@H](O4)C)N(C)C

ACTOXUHEUCPTEW-CEUOBAOPSA-N

InChI=1S/C43H74N2O14/c1-24-21-29(19-20-46)39(59-42-37(49)36(45(9)10)38(27(4)56-42)58-35-23-43(6,51)41(50)28(5)55-35)40(52-11)31(47)22-33(48)53-25(2)15-13-12-14-16-32(24)57-34-18-17-30(44(7)8)26(3)54-34/h12-14,16,20,24-32,34-42,47,49-51H,15,17-19,21-23H2,1-11H3/b13-12+,16-14+/t24-,25-,26-,27-,28+,29+,30+,31-,32+,34+,35+,36-,37-,38-,39+,40+,41+,42+,43-/m1/s1

2-[(4R,5S,6S,7R,9R,10R,11E,13E,16R)-6-[(2S,3R,4R,5S,6R)-5-[(2S,4R,5S,6S)-4,5-dihydroxy-4,6-dimethyloxan-2-yl]oxy-4-(dimethylamino)-3-hydroxy-6-methyloxan-2-yl]oxy-10-[(2R,5S,6R)-5-(dimethylamino)-6-methyloxan-2-yl]oxy-4-hydroxy-5-methoxy-9,16-dimethyl-2-oxo-1-oxacyclohexadeca-11,13-dien-7-yl]acetaldehyde

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)

DMSO : ~100 mg/mL (~118.62 mM)

Solubility in Formulation 1: ≥ 2.5 mg/mL (2.97 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.5 mg/mL (2.97 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
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.

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Solubility in Formulation 3: ≥ 2.5 mg/mL (2.97 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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