Vibramycin Mechanism of Action

Pharmacology: Pharmacodynamics: Doxycycline is primarily bacteriostatic and is thought to exert its antimicrobial effect by the inhibition of protein synthesis. Doxycycline is active against a wide range of gram-positive and gram-negative microorganisms, including: Gram-Negative Bacteria: Acinetobacter species (formerly Mima and Herellea species); Bacteroides species; Bartonella bacilliformis; Brucella species; Calymmatobacterium granulomatis; Campylobacter fetus; Enterobacter aerogenes; Escherichia coli; Francisella tularensis (formerly Pasteurella tularensis); Haemophilus ducreyi; Haemophilus influenzae; Klebsiella species; Moraxella catarrhalis; Neisseria gonorrhoeae; Shigella species; Vibrio cholera (formerly Vibrio comma); Yersinia Pestis (formerly Pasteurella pestis).
Gram-Positive Bacteria: Alpha-hemolytic streptococci (viridans groups); Enterococcus groups (S. faecalis and S. faecium); Streptococcus pneumoniae; Streptococcus pyogenes.
Other Microorganisms: Actinomyces species; Bacillus anthracis; Balantidium coli; Borrelia burgdorferi; Borrelia duttonii; Borrelia recurrentis; Chlamydia psittaci; Chlamydia trachomatis; Clostridium species; Entamoeba species; Fusobacterium species; Leptotrichia buccalis (formerly Fusobacterium fusiforme); Leptospira species; Listeria monocytogenes; Mycoplasma pneumoniae; Plasmodium falciparum (asexual erythrocytic forms only); Propionibacterium acnes; Rickettsiae; Treponema pallidum; Treponema pertenue; Ureaplasma urealyticum.
Pharmacokinetics: Tetracyclines are readily absorbed and are bound to plasma proteins in varying degree. They are concentrated by the liver in the bile, and excreted in the urine and feces at high concentrations and in a biologically active form. Doxycycline is virtually completely absorbed after oral administration. Studies reported to date indicate that the absorption of doxycycline, unlike certain other tetracyclines, is not notably influenced by the ingestion of food or milk.
Following a 200 mg dose, normal adult volunteers averaged peak serum levels of 2.6 mcg/ml of doxycycline at two hours, decreasing to 1.45 mcg/ml at 24 hours. Excretion of doxycycline by the kidney is about 40%/72 hours in individuals with normal renal function (creatinine clearance about 75 ml/min). This percentage excretion may fall to a range as low as 1%-5%/72 hours in individuals with severe renal insufficiency (creatinine clearance below 10 ml/min). Studies have shown no significant difference in serum half-life of doxycycline (range: 18 to 22 hours) in individuals with normal and severely impaired renal function.
Children and Adolescents (2 to 18 years of age).
Population pharmacokinetic analysis of sparse concentration-time data of doxycycline following standard of care intravenous (IV) and oral dosing in 44 pediatric patients (2-18 years of age) showed that allometrically-scaled clearance (CL) of doxycycline in pediatric patients ≥2 to ≤8 years of age (median [range] 3.58 [2.27-10.82] L/h/70 kg, N=11) did not differ significantly from pediatric patients >8 to 18 years of age (3.27 [1.11-8.12] L/h/70 kg, N=33). For pediatric patients weighing ≤45 kg, body weight normalized doxycycline CL in those ≥2 to ≤8 years of age (median [range] 0.071 [0.041-0.202] L/kg/h, N=10) did not differ significantly from those >8 to 18 years of age (0.081 [0.035-0.126] L/kg/h, N=8). In pediatric patients weighing >45 kg, no clinically significant differences in body weight normalized doxycycline CL were observed between those ≥2 to ≤8 years (0.050 L/kg/h, N=1) and those >8 to 18 years of age (0.044 [0.014 0.121] L/kg/h, N=25). No clinically significant difference in CL between oral and IV dosing was observed in the small cohort of pediatric patients who received the oral (N=19) or IV (N=21) formulation alone.
Toxicology: Preclinical Safety Data: Long-term studies in animals to evaluate carcinogenic potential of doxycycline have not been conducted. However, there has been evidence of oncogenic activity in rats in studies with the related antibiotics, oxytetracycline (adrenal and pituitary tumors) and minocycline (thyroid tumors).
Likewise, although mutagenicity studies of doxycycline have not been conducted, positive results in in vitro mammalian cell assays have been reported for related antibiotics (tetracycline, oxytetracyline).
Doxycycline administered orally at dosage levels as high as 250 mg/kg/day had no apparent effect on the fertility of female rats. Effect on male fertility has not been studied.