Clindamycin

Clindamycin is formed by substituting a chlorine atom for the 7-hydroxy substituent of the naturally occurring lincosamide antibiotic lincomy-cin (Fig. 6.9). Both compounds contain the unusual sulfur-containing sugar moiety methyl-thiolincosamide. Clindamycin is used to treat anaerobes, protozoa, and some methicillin resistant S. aureus infections and is applied topically 

Diagnostic tests for clindamycin-induced hypersensitivities have not been widely employed and validated. No clindamycin-specific IgE antibodies have been found nor have any allergenic 

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Lincomycin. The liacomycias and celesticetins are a small family of antibiotics that have carbohydrate-type stmctures. Clindamycin, a chemical modification of lincomycin, is clinically superior. Antibiotics ia this family inhibit gram-positive aerobic and anaerobic bacteria by interfering with proteia biosyathesis. 

Qindamycin, 7(5)-7-chloro-7-deoxyliQcomycin [18323-44-9] (1, R = H, R = Q), also known as Cleocin, first resulted from the reaction of lincomycin and thionyl chloride (54) improved synthetic methods involve the reaction of lincomycin and triphenylphosphine dichloride or triphenylphosphine in carbon tetrachloride (55). Clindamycin is significantly more active than lincomycin against gram-positive bacteria in vitro, and is absorbed rapidly following oral adnainistration. Clindamycin 2-palmitate [36688-78-5], (6, R = R = OC(CH2) 4CH2), 2-palmitate ester of clindamycin, is... 

Antibacterial activity of clindamycin is found both in urine and feces after adrninistration of clindamycin. This activity is a consequence of the presence of both clindamycin and its metaboUte, de- /V-methy1c1indamycin [22431-45-4] (6, R = R = H). Unlike de-/V-methy11incomycin, the de-Ai-methyl analogue is as active in vitro as clindamycin. The analogue has been isolated from the urine of humans who had received clindamycin, and its presence in semm has been detected (65). 

Clindamycin has found use in the treatment of common infections caused by gram-positive cocci It is also efficacious in the treatment of anaerobic infections, including actinomycosis (38). Clindamycin has been shown to be active against strains of P/asmodiumin animals (66—68). 

Cross-resistance between lincomycin and clindamycin is complete (64), and co-resistances of lincomycin also apply to clindamycin. However, the inactivation of clindamycin by clinical isolates of Staphylococcus haemolyticus and Staphylococcus aureus is caused by adenylylation at the 4-position to form clindamycin 4-(5 -adenylate) [29752-38-3] (7) in contrast to the lincomycin 3-(5 -adenylate) [117785-83-8] (8) that forms (26). 

When added to fermentations of Streptomjcespunipalus clindamycin is converted into de-A/-methylclindamycin (6, R = R = H). However, when clindamycin is incubated with Streptomjces armentosus clindamycin sulfoxide [68366-52-9] C gH23ClN20gS, which has low antibacterial activity, is formed... 

Clindamycin 3-phosphate [28708-34-17, antibacterially inactive in vitro, and the ribonucleotides clindamycin 3-(5 -cytidylate) [31186-90-0], clindamycin 3-(5 -adenylate) [31186-91-1], clindamycin 3-(5 -uridylate) [36010-69-2], and clindamycin 3-(5 -guanylate) [36010-70-5], all inactive in vitro, can be generated... 

All of these derivatives protect mice infected with Staphylococcus aureus, however, presumably because of bio transformation into clindamycin (71—73). 

Similar stmcture activity relationships were found in the 4 -alkyl analogues of clindamycin (87). The de- /V-methylclindamycin intermediates including de- /V-methylclindamycin itself, but unlike de-/V-methyllincomycin, are also highly active antibacterially. In addition, they are active in vivo as antknalarial agents (66—68). 

It is estimated (99) that U.S. sales of clindamycin in 1989 were 45 million. Clindamycin was the seventh most widely used of all prescription products in U.S. hospitals (100). Figures are not available for worldwide sales of clindamycin, or for sales of lincomycin, which are virtually all outside the United States. 

The composition of matter patents in the United States issued to The Upjohn Company on clindamycin phosphate and hydrochloride expired at the end of 1986 and in early 1987, respectively. Since then, these compounds have been available genericaHy from more than two dozen companies in the United States alone (101,102). 

Some antibiotics, such as the tetracyclines, tetracycline (7), doxycycline (78), and minocycline (17), chloramphenicol (79), and clindamycin (23) have modest antimalarial properties, but are slow-acting. 

In recent years, many parent dmgs have been converted to esters to generate so-called prodmgs ia order to overcome some undesirable property such as bitter taste, poor absorption, poor solubiUty, and irritation at site of iajection. For example, antibiotics such as chloramphenicol [56-75-7] and clindamycin [18323-44-9] have been derivatized as their palmitate esters ia order to minimise their bitter taste. 

Aminoglycosides Tetracyclines Chloramphenicol Erythromycin Clindamycin Spectinomycin Mupirodn Fusldfc add Inhibition of protein biosynthesis... 

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