Doxycycline [HSA-Biotin]

Doxycycline, which appears as yellow crystals at room temperature, is clinically a tetracyclic antibiotic and has good clinical effects. Tetracyclines are α-tetracene derivatives. The key to the different biological properties of these drugs lies in the different substituents at the 5, 6, and 7 positions of the tetracycline core. Compared with similar drugs, doxycycline hydrochloride has better lipid solubility due to its different 5 and 6 substituents in the tetracycline core, which greatly improves the penetration ability through biological membranes, rapid absorption and wide distribution in the body, and its antibacterial properties The activity is also enhanced, showing that it can produce a bactericidal effect on bacteria. Therefore, the use of doxycycline hydrochloride can also reduce the occurrence of drug-resistant strains, while showing no obvious cross-resistance with natural tetracyclines, and the elimination half-life t1/2β of metabolism in the body is as long as 15~22 hours, and its persistence the therapeutic effect is better. Doxycycline's mechanism is the same as that of tetracycline, mainly interfering with protein synthesis of sensitive bacteria. It can specifically bind to the 30S subunit of bacterial ribosomes at the A position, thereby inhibiting the connection of aminoacyl-tRNA at this position and preventing the elongation of the peptide chain; doxycycline can also change the permeability of bacterial cell membranes, it causes the leakage of nucleotides and other important components in cells, thereby inhibiting the replication of bacterial DNA. Doxycycline is effective against Staphylococcus aureus, Streptococcus pneumoniae, Streptococcus pyogenes, Neisseria gonorrhoeae, meningococci, Escherichia coli, Aerobacter aerogenes, Shigella, Yersinia, Listeria monocytogenes, etc. It has strong antibacterial activity and has certain effects on rickettsia, mycoplasma, chlamydia, actinomycetes, etc. The antibacterial spectrum is basically the same as that of tetracycline and oxytetracycline. Both internal and external antibacterial effects are stronger than those of tetracycline. Microorganisms have close cross-resistance to doxycycline, tetracycline, oxytetracycline, etc.

Figure 1. Experimental and therapeutic use of doxycycline carries the risk of altering mitochondrial function and organismal physiology. (Source: Chatzispyrou IA,et al., 2015)

Carcinogenicity: SD rats were orally administered 20, 75 and 200 mg/kg for 2 consecutive years. As a result, 200 mg/kg caused uterine polyps in female rats. No relevant tumors were seen in male animals in the 200mg/kg group. Genotoxicity: CHO/HGPRT mutation test and micronucleus test were negative. Reproductive toxicity: Orally administered to SD rats ≥50 mg/kg/d (equivalent to 10 times the human daily clinical dose based on body surface area), it can reduce sperm motility and concentration, cause sperm morphology abnormalities, and increase the risk of implantation. Doxycyclinet causes reproductive toxicity at all doses. Although this product damaged the fertility of rats, its effect on human fertility is unclear.

Doxycycline is completely absorbed after oral administration and can absorb more than 90% of the administered dose. Plasma concentrations are almost the same for oral and parenteral administration. Take 100 mg orally, and the peak plasma concentration is about 1.8 to 2.9 mg/L. After absorption, the drug is widely distributed in various tissues and body fluids, with a distribution volume of approximately 0.7L/kg. Due to its high fat solubility, doxycycline has strong penetration into tissues. The drug concentration in thoracic duct lymph, peritoneal effusion, intestinal tissue, eye and prostate tissue is high, about 60% to 75% of the blood concentration, the drug concentration in bile can reach 10 to 20 times the blood concentration; higher drug concentrations can also be reached in breast milk; doxycycline can also be distributed in the liver, spleen, bone marrow, bones, In dentin and enamel. The protein binding rate of doxycycline in the body is 80% to 95%, and the elimination half-life is 12 to 22 hours. The half-life is not significantly prolonged in patients with renal impairment. The drug is mainly metabolized and inactivated in the liver and excreted in the urine through glomerular filtration. When renal function is damaged, the excretion of doxycycline from the gastrointestinal tract increases and becomes the main metabolic pathway. Doxycycline is not removed by dialysis.

Vibramycin