Following a single dose of Minocin 200 mg administered intravenously to 10 healthy male subjects, serum concentrations of minocycline ranged from 2.52 to 6.63 mcg/mL (average 4.18 mcg/mL) at the end of infusion and 0.82 to 2.64 mcg/mL (average 1.38 mcg/mL) after 12 hours. In a group of 5 healthy male subjects, serum concentrations of minocycline ranged from 1.4 to1.8 mcg/mL at the end of the dosing interval following administration of Minocin 100 mg every 12 hours for three days. When Minocin 200 mg once daily was administered for three days, serum concentrations of minocycline were approximately 1 mcg/mL at 24 hours. The serum elimination half-life of minocycline following administration of either Minocin 100 mg every 12 hours or 200 mg once daily was not significantly different and ranged from 15 to 23 hours.
The serum elimination half-life of minocycline ranged from 11 to 16 hours in subjects with hepatic impairment (n=7) and 18 to 69 hours in subjects with renal impairment (n=5). In comparison, the serum elimination half-life of minocycline ranged from 11 to 17 hours following a single dose of oral minocycline 200 mg in healthy subjects (n=12).
Microbiology
Mechanism of Action
The tetracyclines are primarily bacteriostatic and are thought to exert their antimicrobial effect by the inibition of protein synthesis. The tetracyclines, including minocycline, have a similar antimicrobial spectrum of activity against a wide range of Gram-positive and Gram-negative bacteria. Cross-resistance of these bacteria to tetracyclines is common.
List of Microorganisms
Minocycline has been shown to be active against most isolates of the following bacteria, both in vito and in clinical infections as described in the INDICATIONS AND USAGE section:
Gram-positive Bacteria
Bacillus anthracis
Listeria monocytogenes
Staphylococcus aureus
Streptococcus pneumoniae
Gram-negative Bacteria
Bartonella bacilliformis
Brucella species
Klebsiella granulomatis
Campylobacter fetus
Francisella tularensis
Vibrio cholerae
Yersinia pestis
Acinetobacter species
Enterobacter aerogenes
Escherichia coli
Haemophilus influenzae
Klebsiella species
Neisseria meningitidis
Shigella species
Other Microorganisms
Actinomyces species
Borrelia recurrentis
Chlamydophila psittaci
Chlamydia trachomatis
Clostridium species
Entamoeba species
Fusobacterium nucleatum subspecies fusiforme
Mycobacterium marinum
Mycoplasma pneumoniae
Propionibacterium acnes
Rickettsiae
Treponema pallidum subspecies pallidum
Treponema pallidum subspecies pertenue
Ureaplasma urealyticum
Susceptibility Test Methods
When available, the clinical microbiology laboratory should provide the results of in vitro susceptibility test results for antimicrobial drugs used in resident hospitals to the physician as periodic reports that describe the susceptibility profile of nosocomial and community-acquired pathogens. These reports should aid the physician in selecting an antibacterial drug for treatment.
Dilution Techniques
Quantitative methods are used to determine antimicrobial minimal inhibitory concentrations (MICs). These MICs provide estimates of the susceptibility of bacteria to antimicrobial compounds. The MICs should be determined using a standardized method (broth or agar) or equivalent with standardized inoculum concentrations and standardized concentrations of tetracycline or minocycline powder.1,2 The MIC values should be interpreted according to the criteria provided in Table 1.
Diffusion techniques
Quantitative methods that require measurement of zone diameters also provide reproducible estimates of the susceptibility of bacteria to antimicrobial compounds. The zone size provides an estimate of the susceptibility of bacteria to antimicrobial compounds. The zone size should be determined using a standardized method.2,3 This procedure uses paper disks impregnated with 30 mcg tetracycline or 30 mcg minocycline to test the susceptibility of microorganisms to minocycline. The disk diffusion interpretive criteria are provided in Table 1.
a Organisms that are susceptible to tetracycline are also considered susceptible to minocycline. However, some organisms that are intermediate or resistant to tetracycline may be susceptible to minocycline.
b The current absence of resistance isolates precludes defining any result other than “susceptible”. If isolates yielding MIC results other than susceptible, they should be submitted to a reference laboratory for further testing.
A report of “Susceptible” indicates that the antimicrobial drug is likely to inhibit growth of the microorganism if the antimicrobial compound reaches the concentrations usually achievable at the site of infection. A report of “Intermediate” indicates that the result should be considered equivocal, and, if the microorganism is not fully susceptible to alternative, clinically feasible drugs, the test should be repeated. This category implies possible clinical applicability in body sites where the drug is physiologically concentrated or in situations where high dosage of drug can be used. This category also provides a buffer zone which prevents small uncontrolled technical factors from causing major discrepancies in interpretation. A report of “Resistant” indicates that the antimicrobial drug is not likely to inhibit growth of the microorganism, if the antimicrobial drug reaches the concentrations usually achievable at the site of infection; other therapy should be selected.
Quality Control
Standardized susceptibility test procedures require the use of laboratory controls to monitor and ensure the accuracy and precision of supplies and reagents used in the assay, and the techniques of the individuals performing the test 1,2,3. Standard tetracycline (class compound) or minocycline powder should provide the following range of MIC values noted in Table 2. For the disc diffusion technique, using the 30 mcg tetracycline or 30 mcg minocycline disk, the criteria in Table 2 should be achieved.
