Tetracyclines demethylchlortetracycline

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).

Administration of 100 mg doxycycline, in the absence of foods, led to almost complete absorption from the gut and a peak blood level of 1-8 Mg/ml two hours after ingestion. Three times this dose was required.to produce a similar blood level in four hours in the case of 300 mg demethylchlortetracycline. The plasma half-life (after single dose) was 15 hours in the case of doxycycline and 12 hours for demethylchlortetracycline. This means that the half-life of doxycycline is seven hours longer than that of tetracycline. 

The presence of tetracyclines in urine and plasma can be readily and sensitively determined (321). Doxycycline, tetracycline, oxytetracycline, demethylchlortetracycline, and jnethacycline analyses were found to be highly sensitive to the pH of the medium (322). Determination of amino-... 

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 possible effects of such modifications are of several kinds, some not directly concerned with therapeutic efficacy. In its new form the antibiotic may be more stable, more soluble, more palatable (chloramphenicol palmitate), better absorbed (erythromycin estolate), or less irritant to the tissues (polymyxin methane sulfonate). Some of the most far-reaching effects produced by a minor structural change are seen in demethylchlortetracycline, which, as compared with tetracycline, is more stable, antibacterially more active, and much more slowly excreted. 

The most important drugs with sensitizing effects are listed in Table 4. Tetracyclines, in particular demethylchlortetracycline, are commonly responsible for photodermatitis. However, this action does not have any immunological basis, but depends on a phototoxic effect (Harder et al. 1961 Maibach et al. 1967), similar to that produced by psoralens, certain dyes, cadmium sulphide, etc. 

The tetracyclines are a group of antibiotics with the same basic chemical structure they are derivatives of the naphthacene ring system. Compounds of the series differ in the composition of the side chains (Fig. 1). These antibiotics derived from different Streptomyces species show closely related spectra of bacteriostatic properties, with the exception of minocycline, which is very effective against most Staphylococcus strains resistant to other tetracyclines. Absorption, metabolism, and excretion of the different tetracyclines vary, however. After oral application, tetracycline, oxytetracycline, and chlortetracycline are absorbed to a much lesser degree than demethylchlortetracycline, methacycline, or the almost entirely absorbed minocycline. Maximum blood levels are found 2-6 h after oral intake and immediately in the case of intravenous infusion. Half-lives between 8 and 15 h were reported. The tetracyclines diffuse readily across the vascular barrier and are found in various tissues such as the liver, spleen, bone marrow, kidney, skin, and lungs as well as the peritoneal and pericardiac cavities. The tetracyclines are also able to... 

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... 

Simultaneous chlortetraQrcline, demethylchlortetracycline, methaQrcline, oxytetracycline, tetracycline... 

Tetracyclines are widely used in honeybee culture for preventing foul brood of honeybees. Therefore a TLC method for residue analysis of the tetracylines OTC, TC, CTC, DC, methacycline, demethylchlortetracycline, and minocycline in honey was established (50). In this method 25 g of... 

From starting line iso-tetracycline, epi-tetra-cycline, epi-chlortetracycline, iso-chlortetracyc-line, tetracycline, hydroxytetracycline, demethylchlortetracycline, chlortetracycline, anhydrotetracycline, anhydrochlortetracycline Ref. 

ED 1369 is a point-blocked mutant derived from a demethylchlortetracycline-producing parent and is thus also blocked for the C-6-methylation step (J. R. D. McCormick et al., 1965b). It makes no tetracycline antibiotic. 

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