CLINICAL PHARMACOLOGY
Doxycycline is primarily bacteriostatic and 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 organisms.
The drugs in the tetracycline class have closely similar antimicrobial spectra, and cross resistance among them is common. Microorganisms may be considered susceptible to doxycycline (likely to respond to doxycycline therapy) if the minimum inhibitory concentration (M.I.C.) is not more than 4 mcg/mL. Microorganisms may be considered intermediate (harboring partial resistance) if the M.I.C. is 4 to 12.5 mcg/mL and resistant (not likely to respond to therapy) if the M.I.C. is greater than 12.5 mcg/mL.
Susceptibility Plate Testing: If the Kirby-Bauer method of disc susceptibility is used, a 30 mcg doxycycline disc should give a zone of at least 16 mm when tested against a doxycycline-susceptible strain. A tetracycline disc may be used to determine microbial susceptibility. If the Kirby-Bauer method of disc susceptibility is used, a 30 mcg tetracycline disc should give a zone of at least 19 mm when tested against a tetracycline-susceptible bacterial strain.
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.
Following a 100 mg single dose administered in a concentration of 0.4 mg/mL in a one-hour infusion, normal adult volunteers average a peak of 2.5 mcg/mL, while 200 mg of a concentration of 0.4 mg/mL administered over two hours average a peak of 3.6 mcg/mL.
Excretion of doxycycline by the kidney is about 40 percent/72 hours in individuals with normal function (creatinine clearance about 75 mL/min). This percentage excretion may fall as low as 1 to 5 percent/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.
Hemodialysis does not alter this serum half-life of doxycycline.
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