Minocycline is a semisynthetic tetracycline developed by Lederle in 1972, and marketed under the brand name Minocin .
Minocycline is a broad-spectrum tetracycline antibiotic, and has a broader spectrum than the other members of the group. It is a bacteriostatic antibiotic, classified as a long-acting type. As a result of its long half-life it generally has serum levels 24 times that of the simple water-soluble tetracyclines.
Minocycline is the most lipid-soluble of the tetracycline-class antibiotics, giving it the greatest penetration into the prostate and brain, but also the greatest amount of central nervous system (CNS)-related side effects, such as vertigo.
Minocycline and doxycycline are frequently used for the treatment of acne vulgaris. Both of these closely related antibiotics have similar levels of efficacy, although doxycycline has a slightly lower risk of adverse side effects. Historically, minocycline has been a very effective treatment for acne vulgaris . However, acne that is caused by antibiotic resistant bacteria is a growing problem in many countries . The therapeutic use of minocycline includes the treatment of infections caused by susceptible strains of microorganisms, such as Rocky Mountain spotted fever, typhus fever and the typhus group, Q fever, rickettsial pox and tick fevers caused by Rickettsiae, upper respiratory tract infections caused by Streptococcus pneumoniae and for the treatment of asymptomatic carriers of Neisseria meningitidis.
Minocycline is also used for other skin infections such as MRSA  as well as Lyme disease , using a dosing regimen of twice daily 100 mg. Its activity against Lyme disease is enhanced by its superior ability to cross the blood-brain barrier. It may be used to treat drug resistant acinetobacter infections .
Both minocycline and doxycycline have shown effectiveness in asthma due to immune suppressing effects. Minocycline as well as doxycycline have modest effectiveness in treating rheumatoid arthritis. It is recognized as a Disease-Modifying Anti-Rheumatic Drug by the American College of Rheumatology, which recommends its use as a treatment for rheumatoid arthritis.
Dosage and Administration
Minocycline has been observed to cause a dark discoloration of the thyroid in experimental animals (rats, minipigs, dogs and monkeys). In the rat, chronic treatment with minocycline has resulted in goiter accompanied by elevated radioactive iodine uptake and evidence of thyroid tumor production. Minocycline has also been found to produce thyroid hyperplasia in rats and dogs.
LD50=2380 mg/kg (rat, oral), LD50=3600 mg/kg (mouse, oral).
Uncommon side effects (with prolonged therapy) include skin discolouration and autoimmune disorders that are not seen with other drugs in the class. Minocycline can cause the rare condition of secondary intracranial hypertension which has initial symptoms of headache, visual disturbances, dizziness, vomiting, and confusion. Cerebral edema, as well as autoimmune rheumatoid arthritis are rare side effects to minocycline in some people .
Minocycline may cause upset stomach,
diarrhea, dizziness, unsteadiness, drowsiness, mouth sores, headache and
vomiting. Minocycline increases sensitivity to sunlight. It has also been linked
to cases of lupus. Minocycline can reduce the effectiveness of oral
contraceptives. Prolonged use of minocycline over an extended period of time
can lead to blue-gray skin and blue-gray staining of scar tissue is not
permanent but it can take a very long time for the skin colour to return to
normal; on the other hand a muddy brown skin colour in sun exposed areas is
usually a permanent skin discolouration. Permanent blue discoloration of
gums or teeth discoloration may also occur. Rare but serious side effects
include fever, yellowing of the eyes or skin, stomach pain, sore throat, vision
changes, and mental changes, including depersonalization .
There are no data on the effects of age, sex, changes in body mass, co-morbidity or infection on the pharmacokinetics of minocycline except for a small number of studies carried out in patients with renal impairment and end stage renal disease. Renal impairment and end stage renal disease have little effect on the serum concentrations and serum half-life or AUC of minocycline [24, 25, 30, 31] in both single dose and short multi-dosing studies.
Table 1. Pharmacokinetic of minocycline
Minocycline is almost completely absorbed (95100%) , mainly in the stomach, duodenum and jejunum. Unlike other tetracyclines, food does not appear to have an effect on either the Cmax or AUC . The Cmax increases dose proportionally: 0.65 mg/L after 50 mg, 2.2 mg/L after 150 mg, and 33.6 mg/L after a 200 mg dose [19-22]. Absorption is reduced by iron and antacids containing calcium and magnesium .
There is little data on the volume of distribution of minocycline, values of 80115 L have been reported  or 1.17 L/kg . As with other tetracyclines, there is very little good quality data on tissue penetration. However, a tissue/serum concentration ratio of >10 has been reported for liver and bile; 510 for duodenum, gall bladder and thyroid; and <2 for colon, bladder, prostate, uterus, breast, skin, lymph nodes and veins . No minocycline has been detected in saliva and concentrations of <50% serum in CSF have been reported .
The amount of minocycline recovered in the urine is about 512% of the dose. Faecal elimination accounts for about 2035% of the dose [21, 24, 26, 28]. Renal clearance is about 2.21.2 mL/min .
Up to six metabolites of minocycline have been described, some of which have antibacterial activity and are found in urine. The principal metabolite is 9-hydroxyminocycline; the other two main metabolites are mono-N-demethylated derivatives. Epimerization of minocycline also results in the formation of 4-epiminocycline.
Mechanism of action
Minocycline passes directly through the lipid bilayer or passively diffuses through porin channels in the bacterial membrane. Tetracyclines like minocycline bind to the 30S ribosomal subunit, preventing the binding of tRNA to the mRNA-ribosome complex and interfering with protein synthesis.
Minocycline produced a 1.5 ± 1.0 log kill against S. aureus, 2.0 ± 0.8 log kill against E. coli and +0.3 ± 1.8 log growth with K. pneumoniae. MBCs (mg/ml) are 2-fold higher than the MIC for S. pneumoniae and 24 times the MIC for S. aureus.
Using a hollow fibre in vitro model to simulate free drug serum concentrations of oral minocycline 200 mg/day in man, the 24 hrs antibacterial effect was a 1.8 ± 0.2 log reduction in count by 24 h against MRSA .
CAS number: 10118-90-8 EINECS:
Molecular Formula: C23H27N3O7
Average mass: 457.47641 Da
Monoisotopic mass: 457.184906 Da
Systematic name: (4S,4aS,5aR,12aS)-4,7-Bis(dimethylamino)-3,10,12,12a-tetrahydroxy-1,11-dioxo-1,4,4a,5,5a,6,11,12a-octahydro-2-tetracenecarboxamide
Std. InChI: 1S/C23H27N3O7/c1-25(2)12-5-6-13(27)15-10(12)7-9-8-11-17(26(3)4)19(29)16(22(24)32)21(31)23(11,33)20(30)14(9)18(15)28/h5-6,9,11,17,27,29-30,33H,7-8H2,1-4H3,(H2,24,32)/t9-,11-,17-,23-/m0/s1
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