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Pharmacokinetics

The absorption of demeclocycline is slower than that of tetracycline. The time to reach the peak concentration is about 4 hours. After a 150 mg oral dose of demeclocycline tablet, the mean concentrations at 1 hour and 3 hours are 0.46 and 1.22 µg/mL (n = 6), respectively, The serum half-life ranges between 10 and 16 hours. When demeclocycline hydrochloride is given concomitantly with some dairy products, or antacids containing aluminum, calcium, or magnesium, the extent of absorption is reduced by more than 50%. Demeclocycline hydrochloride penetrates well into various body fluids and tissues. The percent of demeclocycline hydrochloride bound to plasma protein is about 40% using a dialysis equilibrium method and 90% using an ultra-filtration method. Demeclocycline hydrochloride, like other tetracyclines, is concentrated in the liver and excreted into the bile where it is found in much higher concentrations than in the blood. The rate of demeclocycline hydrochloride renal clearance (35mL/min/1.73 m²) is less than half that of tetracycline. Following a single 150 mg dose of demeclocycline hydrochloride in normal volunteers, 44% (n = 8) was excreted in urine and 13% and 46%, respectively, were excreted in feces in two patients within 96 hours as active drug.

Microbiology

The tetracyclines are primarily bacteriostatic and are thought to exert their antimicrobial effect by the inhibition of protein synthesis. The tetracyclines, including demeclocycline, have a similar antimicrobial spectrum of activity against a wide range of gram-negative and gram- positive organisms. Cross-resistance of these organisms to tetracyclines is common.

Demeclocycline has been shown to be active against most strains of the following microorganisms, both in vitro and in clinical infections as described in the INDICATIONS AND USAGE section.

AEEROBIC GRAM-POSITIVE MICROORGANISMS:

Bacillus anthracis
Listeria monocytogenes                                                 
Staphylococcus aureus
Streptococcus pneumoniae

AEROBIC GRAM-NEGATIVE MICROORGANISMS:

Bartonella bacilliformis
Brucella species
Calymmatobacterium granulomatis
Campylobacter fetus
Francisella tularensis
Haemophilus ducreyi
Haemophilus influenzae
Neisseria gonorrhoeae
Vibrio cholerae
Yersinia pestis

Because many strains of the following groups of gram-negative microorganisms have been shown to be resistant to tetracyclines, culture and susceptibility testing are especially recommended;

Acinobacter species
Enterobacter aerogenes
Escherichia coli
Klebsiella species
Shigella species

OTHER MICROORGANISMS:

Actinomyces israelii
Borrelia recurrentis
Chlamydia psittaci
Chlamydia trachomatis
Clostridium species
Entamoeba mobs
Fusobacterium fusiforme
Mycoplasma pneumoniae
Propionibacterium acnes
Rickettsiae
Treponema pallidum subspecies pallidum
Treponema pallidum subspecies pertenue
Ureaplasma urealyticum
Shigella species

OTHER MICROORGANISMS:

Actinomyces israelii
Borrelia recurrentisChlamydia psittaci
Chlamydia trachomatis
Clostridium species
Entamoeba species
Fusobacterium fusiforme
Mycoplasma pneumoniae
Propionibacterium acnes
Rickettsiae
Treponema pallidum subspecies pallidum
Treponema pallidum subspecies pertenue
Ureaplasma urealyticum

Susceptibility Tests

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 procedure. Standardized procedures are based on a dilution method (broth or agar) or equivalent with standardized inoculum concentrations and standardized concentrations of demeclocycline hydrochloride or tetracycline powder.¹ The MIC values should be interpreted according to the following criteria;

For organisms other than Haemophilus species, Neisseria gonorrhoeae and Streptococcus species:²

A report of "Susceptible" indicates that the pathogen is likely to be inhibited by usually achievable concentrations of the antimicrobial compound in blood. 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 usually achievable concentrations of the antimicrobial compound in the blood are unlikely to be inhibitory and that other therapy should be selected,

Standardized susceptibility test procedures require the use of laboratory control microorganisms to control the technical aspects of the laboratory procedures. Standard demeclocycline or tetracycline powder should provide the following MIC values;2

Diffusion Techniques

Quantitative methods that require measurement of zone diameters also provide reproducible estimates of the susceptibility of bacteria to antimicrobial compounds. One such standardized procedure requires the use of standardized inoculum concentrations.² This procedure uses paper disks impregnated with 30-µg tetracycline (as a class disk) or a 30-µg demeclocycline hydrochloride disk to test the susceptibility of microorganisms to demeclocycline. Reports from the laboratory providing results of the standard single-disk susceptibility test with either a 30-µg tetracycline-class disk or a 30-µg demeclocycline disk should be interpreted according to the following criteria: For organisms other than Haemophilus species, Neisseria gonorrhoeae and Streptococcus species:²

Interpretation should be as stated above for results using dilution techniques, Interpretation involves correlation of the diameter obtained in the disk test with the MIC for demeclocycline hydrochloride or tetracycline.

As with standardized dilution techniques, diffusion methods require the use of laboratory control microorganisms to control the technical aspects of the laboratory procedures. For the diffusion technique, the 30-µg demeclocycline hydrochloride disk or the 30-µg tetracycline-class disk should provide the following zone diameters in these laboratory test quality control strains:²

Animal Pharmacology And Animal Toxicology

Hyperpigmentation of the thyroid has been produced by members of the tetracycline class in the following species: in rats by oxytetracycline, doxycycline, tetracycline P04 and methacycline; in mini pigs by doxycycline, minocycline, tetracycline POa. and methacydine; in dogs by doxycycline and minocycline in monkeys by minocycline,

Minocycline, tetracycline P04, methacycline, doxycycline, tetracycline base, oxytetracycline HCI, and tetracycline HCI were goitrogenic in rats fed a low iodine diet. This goitrogenic effect was accompanied by high radioactive iodine uptake. Administration of minocycline also produced a large goiter with high radioiodine uptake in rats fed a relatively high iodine diet.

Treatment of various animal species with this class of drugs has also resulted in the induction of thyroid hyperplasia in the following: in rats and dogs (minocycline), in chickens (chlortetracycline), and in cats and mice (oxytetracycline). Adrenal gland hyperplasia has been observed in goats and rats treated with oxytetracycline.

REFERENCES

1.  National Committee for Clinical Laboratory Standards. (2000). "Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically. Approved standard M7-A5 and informational supplement M100-S10." National Committee for Clinical Laboratory Standards, Wayne, PA.

2.  National Committee for Clinical Laboratory Standards. (2000). "Performance standards for antimicrobial disk susceptibility tests. Approved Standard m²-A7," National Committee for Clinical Laboratory Standards, Wayne, PA.

3.  National Committee for Clinical Laboratory Standards. (2002). "Performance standards for antimicrobial susceptibility testing. Twelfth informational supplement. M100-S12." National Committee for Clinical Laboratory Standards, Wayne, PA.

Last reviewed on RxList: 6/18/2008
This monograph has been modified to include the generic and brand name in many instances.