Chemical Modification of Clindamycin: Synthesis and Evaluation of Selected Esters

Clindamycin was chemically modified to provide in vivo reversible derivatives that might suitably be utilized in special dosage forms. To improve taste properties, a series of 2- and 3- monoesters and some 2,3-dicarbonate esters of clindamycin were synthesized. A number of highly water-soluble salts were prepared in an attempt to provide an injectable intramuscular preparation with low incidence of pain. The long-chain clindamycin 2-monoesters (palmitate and hexadecylcarbonate) are virtually devoid of the characteristic bitter taste of clindamycin. The water-soluble salts (gluconate and lactobionate) of clindamycin showed no significant improvement over clindamycin in muscle irritation studies. Clindamycin blood levels were determined in dogs following oral administration of some esters. Clindamycin 2-palmitate and clindamycin 2-hexadecylcarbonate exhibited blood levels equivalent to clindamycin hydrochloride. The CD50 results using mice infected with Siaphylococcus aureus showed that several esters possess antibacterial activity equivalent to that of clindamycin hydrochloride.