Doxycycline
DOXYCYCLINE- doxycycline capsule
PharmPak, Inc.
DESCRIPTION
Doxycycline is a broad-spectrum antibacterial synthetically derived from oxytetracycline. Doxycycline capsules USP, 75 mg, and 100 mg contain doxycycline monohydrate equivalent to 75 mg, and 100 mg of doxycycline for oral administration. The chemical designation of the light yellow to pale yellow powder is 2-Naphthacenecarboxamide, 4-(dimethylamino)-1,4,4a,5,5a,6,11,12a-octahydro-3,5,10,12,12a-pentahydroxy-6-methyl-1,11-dioxo-,[4 S -(4a,4a∝,5∝,5a∝,6∝,12a∝,)]-, monohydrate.
Structural formula:
C 22 H 24 N 2 O 8 • H 2 O M.W. = 462.45
Doxycycline has a high degree of lipid solubility and a low affinity for calcium binding. It is highly stable in normal human serum. Doxycycline will not degrade into an epianhydro form.
Inert ingredients: colloidal silicon dioxide; magnesium stearate; microcrystalline cellulose; sodium starch glycolate; and a hard gelatin capsule which contains iron oxide black, iron oxide red, iron oxide yellow, titanium dioxide, gelatin, sodium lauryl sulfate for the 75 mg strength and iron oxide black, iron oxide red, iron oxide yellow, titanium dioxide, FD & C Red # 3, D&C Yellow # 10, gelatin, sodium lauryl sulfate for the 100 mg strength. The capsules are printed with edible ink containing shellac, titanium dioxide, black iron oxide, brown iron oxide and potassium hydroxide for 75 mg and 100 mg strengths.
CLINICAL PHARMACOLOGY
Tetracyclines are readily absorbed and are bound to plasma proteins in varying degrees. They are concentrated by the liver in the bile and excreted in the urine and feces at high concentrations in a biologically active form. Doxycycline is virtually completely absorbed after oral administration.
Following a 200 mg dose of doxycycline monohydrate, 24 normal adult volunteers averaged the following serum concentration values:
Time (hr): | 0.5 | 1.0 | 1.5 | 2.0 | 3.0 | 4.0 | 8.0 | 12.0 | 24.0 | 48.0 | 72.0 |
Conc. | 1.02 | 2.26 | 2.67 | 3.01 | 3.16 | 3.03 | 2.03 | 1.62 | 0.95 | 0.37 | 0.15 (mcg/mL) |
Average Observed Values | |
Maximum Concentration | 3.61 mcg/mL (± 0.9 sd) |
Time of Maximum Concentration | 2.60 hr (± 1.10 sd) |
Elimination Rate Constant | 0.049 per hr (± 0.030 sd) |
Half-Life | 16.33 hr (± 4.53 sd) |
Excretion of doxycycline by the kidney is about 40%/72 hours in individuals with normal function (creatinine clearance about 75 mL/min). This percentage excretion may fall 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.
Hemodialysis does not alter serum half-life.
Microbiology:
Mechanism of Action
Doxycycline inhibits bacterial protein synthesis by binding to the 30S ribosomal subunit. Doxycycline has bacteriostatic activity against a broad range of Gram-positive and Gram-negative bacteria.
Resistance
Cross resistance with other tetracyclines is common.
Antimicrobial Activity
Doxycycline has been shown to be active against most isolates of the following microorganisms, both in vitro and in clinical infections ( see INDICATIONS AND USAGE).
Gram-Negative Bacteria
Acinetobacter species
Bartonella bacilliformis
Brucella species
Campylobacter fetus
Enterobacter aerogenes
Escherichia coli
Francisella tularensis
Haemophilus ducreyi
Haemophilus influenzae
Klebsiella granulomatis
Klebsiella species
Neisseria gonorrhoeae
Shigella species
Vibrio cholera
Yersinia pestis
Gram-Positive Bacteria
Bacillus anthracis
Listeria monocytogenes
Streptococcus pneumoniae
Anaerobic Bacteria
Clostridium species
Fusobacterium fusiforme
Propionibacterium acnes
Other Bacteria
Nocardiae and other
Actinomyces species
Borrelia recurrentis
Chlamydophila psittaci
Chlamydia trachomatis
Mycoplasma pneumoniae
Rickettsiae
Treponema pallidum
Treponema pallidum
subspecies
pertenue
Ureaplasma urealyticum
Parasites
Balantidium coli
Entamoeba species
Susceptibility Testing Methods
When available, the clinical microbiology laboratory should provide cumulative reports of in vitro susceptibility test results for antimicrobial drugs used in local hospitals and practice areas as periodic reports that describe the susceptibility profile of nosocomial and community-acquired pathogens. These reports should aid the physician in selecting the most effective antimicrobial.
Dilution Techniques
Quantitative methods are used to determine antimicrobial minimum inhibitory concentrations (MICs). These MICs provide estimates of the susceptibility of bacteria to antimicrobial compounds. The MICs should be determined using a standardized test method (broth and /or agar). 1,2,4,6,7 The MIC values should be interpreted according to criteria provided in Table 1.
Diffusion Techniques
Quantitative methods that require measurement of zone diameters can also provide reproducible estimates of the susceptibility of bacteria to antimicrobial compounds. The zone size should be determined using a standardized test method. 1,3,4 This procedure uses paper disks impregnated with 30 mcg doxycycline to test the susceptibility of microorganisms to doxycycline. The disk diffusion interpretive criteria are provided in Table 1.
All MedLibrary.org resources are included in as near-original form as possible, meaning that the information from the original provider has been rendered here with only typographical or stylistic modifications and not with any substantive alterations of content, meaning or intent.