Physicochemical and Pharmacologic Properties

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 

The nature of the antigenic determinants is still not properly defined, but it is widely believed that the ring system (Welsh 1955) and the substitution patterns 

Allergic reactions to tetracyclines without exposure to sunlight are uncommon, although various other clinical manifestations may be observed. Approximately 

1%-2% of patients receiving the antibiotics and 1% of people in contact with these drugs in industry show an allergic reaction to the tetracyclines (Kleine-Na-TROP 1956 Weinstein and Welch 1958,1959 Schindel 1965 Olson 1966 Moser 1966 Korossy 1976). 

Fawcett and Pepys (1976) reported the case of a patient who developed immediate bronchospasm and an urticarial reaction after ingestion of a commercial combination of three tetracyclines no reactions could be elicited by oral challenge with the different tetracyclines, tartrazine, or the blue coating of the drug, whereas a provocation test with the commercial preparation was positive. Other clinical patterns, such as fixed drug eruptions (Kandil 1969 Delaney 1970 Csonka et al. 1971 Brown 1974 Shimizu and Shimao 1977 Pasricha and Shukla 1979), vascular purpura (Schoenfeld 1964) and a picture similar to systemic lupus erythematosus (SLE) (Sulkowski and Haserick 1964) have also been described. Contact dermatitis seems to be a very rare complication it was, however, observed after contact with oxytetracycline (Dohn 1962 Bojs and Moller 1974) and minocycline. In the latter case subsequent oral therapy with the same drug was followed by a systemic reaction and the sensitivity was confirmed by epicutaneous tests (Shelley and Heaton 1973). 

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Although there are now many different beta-adrenoceptor antagonists, and the number is still increasing, there are only a few important characteristics that distinguish them in terms of their physicochemical and pharmacological properties Upid solubility, cardioselectivity, partial agonist activity, and membrane-stabilizing activity. The characteristics of the currently available compounds are shown in Table 1. 

Based on the plot of the suppressed hydrogens of the molecular under study, the calculation methods of molecular connectivity indices was developed. It has been used in many fields, such as the studies of correlation between structure and physicochemical and pharmacological properties, especially the relationship between structure and retention behavior, and the evaluation of the hydrophobicities of organic compounds by chromatographic methods. 

B. Sulfonamides Including Benzylpyrimidine Sulfonamides L Physicochemical and Pharmacologic Properties... 

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