Methacycline Doxycycline

Chlortetracy dine Oxytetracycline Tetracycline Demeclocy cline Methacycline Doxycycline Minocycline... 

Fig. 1. Tetracycline (1) and its derivatives chlortetracycline (7-chlorotetracycline) (2) oxytetracycline (5-hydroxytetracycline) (3), demeclocycline (6-demethyl-7-chlorotetracycline) (4) methacycline (6-demethyl-6-deoxy-5-hydroxy-6-methylenetetracycline) (5) doxycycline (6a-deoxy-5-hydroxytetracycline) (6) and minocycline (6-demethy1-6-deoxy-7-dimethy1 amino tetracycline) (7). Substituents at positions not specifically...

Fig. 5.7 Tetracycline antibiotics 1, oxytetracycline 2, chlortetracycline 3, tetracycline 4, demethylchlortetracycline 5, doxycycline 6, methacycline 7, clomocycline 8, minocycline 9, thiacycline (a thiatetracycline with a sulphur atom at 6).

Tetracyclines mainly differ in their absorption after oral administration and their elimination. Absorption after oral administration is approximately 30% for chlortetracycline 60-70% for tetracycline, oxytetracycline, demeclocycline, and methacycline and 95-100% for doxycycline and minocycline. Tigecycline is poorly absorbed orally and must be administered intravenously. A portion of an orally administered dose of tetracycline remains in the gut lumen, modifies intestinal flora, and is excreted in the feces. Absorption occurs mainly in the upper small intestine and is impaired by food (except doxycycline and... 

Tetracyclines are classified as short-acting (chlortetracycline, tetracycline, oxytetracycline), intermediate-acting (demeclocycline and methacycline), or long-acting (doxycycline and minocycline) based on serum half-lives of 6-8 hours, 12 hours, and 16-18 hours, respectively. Tigecycline has a half-life of 36 hours. The almost complete absorption and slow excretion of doxycycline and minocycline allow for once-daily dosing. 

The oral dosage for rapidly excreted tetracyclines, equivalent to tetracycline hydrochloride, is 0.25-0.5 g four times daily for adults and 20-40 mg/kg/d for children (8 years of age and older). For severe systemic infections, the higher dosage is indicated, at least for the first few days. The daily dose is 600 mg for demeclocycline or methacycline, 100 mg once or twice daily for doxycycline, and 100 mg twice daily for minocycline. Doxycycline is the oral tetracycline of choice because it can be given as a once-daily dose and its absorption is not significantly affected by food. All tetracyclines chelate with metals, and none should be orally administered with milk, antacids, or ferrous sulfate. To avoid deposition in growing bones or teeth, tetracyclines should be avoided in pregnant women and children less than 8 years of age. 

Fig. 29.8.1 Chromatograms of a blank kidney sample (A), a kidney sample (B) fortified with 4 ppm of oxytetracycline (—), and 250 ppb of each tetracycline (—), and ultraviolet spectra (C) of the corresponding tetracyclines. Peaks OTC, oxytetracycline TC, tetracycline DMTC, demethylchlortetracycline CTC, chlortetracycline MC, methacycline DC, doxycycline. (From Ref. 296.). 

The three tetracyclines most recently marketed were made by a semisynthetic pathway. The first of these were methacycline (6-methylene oxytetracycline) (5), C22H22N2OS. and its reduction product doxycycline (6). C22H24CIN2O2- The latter compound is a potent antibiotic which is well-absorbed and slowly excreted, thus allowing small and infrequent (once or twice a day) dosage schedules. Finally, the most recent addition to the commercial tetracyclines is minocycline (7). C21H27N3O7. which is also well-absorbed and slowly excreted. 

Oxytetracycline (OTC), tetracycline (TC), and chlortetracycline (CTC) are the main representatives of this antibiotic class. In addition, demeclocycline (DMC), doxycycline (DXC), minocycline (MNC), and methacycline (MTC) can be found in food samples. 

Earlier work on the in situ characterisation of rhodium-phosphine/hydrazine complexes was instrumental in the successful outcome of patent litigation between Hovione (Portugal) and Pfizer (USA). Here, we were able to prove conclusively by P, N, and Rh NMR spectroscopies that in the hydrogenation of doxycycline to methacycline, rhodium complexes with N-donor ligands such as 3 and 4 were involved, rather than [RhCl(PPh3)3]." ... 

Demeclocycline, tetracycline, oxytetracycline, minocycline, and doxycycline are available in the United States for systemic use. Chlortetracycline and oxytetracycline are used in ophthalmic preparations. Methacycline is not available. Other derivatives are available in other countries. The more lipophilic drugs, minocycline and doxycycline, usually are the most active by weight, followed by tetracycline. Resistance of a bacterial strain to any one member of the class may result in cross-resistance to other tetracyclines. Bacterial strains with tetracycline minimum inhibitory concentrations (MICs) of < 4 pg/mL are considered susceptible... 

Dihuidi, K. Kucharski, M.J. Roets, E. Hoogmartens, J. Vanderhaeghe, H. Quantitative anedysis of doxycycline and related substances by high-performance liquid chromatography. J.Chromatogr, 1985, 325, 413-424 [column temp 60 bulk tablets capsules simultaneous impurities, methacycline, oxytetracycline]... 

Structural susceptibilities and structure/activity studies have both inspired a large amount of semi-synthetic vrork to find more stable compounds without loss of antibacterial activity. The less active 6p methyl isomer of doxycycline (6) has been derived from oxytetracycline (3 R = OH) by catalytic reduction.. Treatment of (3) with N-chlorosuccinimide followed by hydrofluoric acid gave the chloro compound (X) which upon catalytic reduction afforded doxycycline (6), the 6a compound together with the less active 6p isomer (refs.250, 251) by saturation of the methylene group and removal of chlorine from (X). Reductive treatment of (X) with sodium hydrosulphite produced methacycline (5). The corresponding 5-deoxy analogues have likewise been derived by using tetracycline (3 R = H) in the same reaction sequences. 

Tetracyclines Chlortetracyline, Demeclocycline, Doxycycline, Lymecycline, Methacycline, Minocycline, Oxytetracycline, Rolitetracycline, letracycline, Tigecycline... 

Similar results were found in 16 other patients taking various combinations of phenytoin, carbamazepine, primidone or phenobarbital. The serum doxycycline levels of almost all of them fell below 0.5 micrograms/mL during the 12 to 24 hour period following their last dose of doxycycline 100 mg. Tetracycline, methacycline, oxytetracycline, demeclocycline and chlortetracycline levels were not significantly affected by these antiepilepties. Other studies confirm this interaction between some barbiturates (amobarbital, pentobarbital, phenobarbital) and doxycycline. ... 

An investigation in 10 healthy subjeets given single oral doses of tetracy-elines showed that ferrous sulfate 200 mg decreased the serum antibacterial levels as follows doxycycline 200 mg, 80 to 90% methacycline 300 mg, 80 to 85% oxytetracycline 500 mg, 50 to 60% and tetracycline 500 mg, 40 to 50%. Another study in 2 groups of 8 healthy subjects found that ferrous sulfate 300 mg reduced the absorption of tetracycline and minocycline by 81% and 77%, respectively. ... 

Because of their chelating action, tetracycline drugs are inactivated in the patient s bowel by any dietary calcium or magnesium ions, whether from milk or from antacid medication. Through such mishaps, many patients have lost the potential benefit of these antibiotics. Tetracyclines are usually given orally. Tetracycline, itself, is still much prescribed, but there are also lower-dose forms available demeclocycline and methacycline, and a sub-class of these which require less frequent dosing doxycycline and minocycline. 

Fig. 1 a-h. Chemical structures of the tetracyclines, a tetracycline b oxytetracycline c chlortetracycline d methacycline e demethylchlortetracycline f 6-deoxytetracycline (doxycycline) g minocycline h roli(A -pyrrolidinomethyl)tetracycline... 

The europium(III) methacycline complex 19 can be used for spectrofluori-metric determination of lysozyme [49]. The oxytetracycline and doxycycline complexes are both sensitive to ATP in that their luminescence emission is increased in presence of ATP [50, 51]. In addition, complex 17 can be used to determine heparin and NADP in aqueous solution [52,53]. The detection of these biomolecules occurs by means of an enhanced fluorescence emission. Bile acid quenches the luminescence of Eu " doxycycline in a concentration dependent manner [54]. 

Catalytic uses of ihodacarbaboranes are represented in die stereoselective hydrogenation of methacycline to give doxycycline. The cluster [3,3-( n2,T]3.C7H7CH2)-c/oso-3,l,2-RhC2B9Hii] proves to be an effective catalyst for this xocess. ... 

Figure 5 Separation of tetracyclines on silicagel HPTLC (A) and RP 8 (B) plates (both Merck). A pre-devel-oping with saturated Na2EDTA-solution and activating for 2 h at I30 C Solvent chloroform-methanol-S% aqueous Naa EDTA (65 20 5, lower layer). B Solvent methanol-acetonitrile-0,5 M oxalic acid (1 1 4, pH = 3.0) 0.1-1.0 pg/spot. Abbreviations MI = minocycline, CTC = chlortetracycline, DMC = demeclocycline, TC = tetracycline, DC = doxycycline, MC = methacycline, OTC = oxytetracycline, RTC = rolitetracycline (unstable).

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