Absorption and urinary excretion of chloramphenicol and 2 analogues, thiocymetin and U-15, 442 in normal men.

Abstract

SummaryComparison of absorption and urinary recovery of chloramphenicol and 2 of its derivatives, Thiocymetin and U-15,442, has been carried out following administration of single oral doses of 500 mg each in 6 healthy human volunteers. Similar peak concentrations of these drugs were noted in serum but they were achieved later after the dose of Thiocymetin. At 25 hours slight antibiotic activity was still discernible with the 2 derivatives, but not with chloramphenicol. In view of the superior antimicrobial activity of chloramphenicol the 2 derivatives are considered to be inferior to the parent compound in producing antimicrobial activity in serum. In contrast, much higher urinary recoveries were achieved with the 2 derivatives than with chloramphenicol. In the case of Thiocymetin urinary recovery was so great as to more than offset its inferior antimicrobial activity; this was not the case with U-15,442. The high recovery of active Thiomycetin in urine suggests that it is inactivated more slowly or by a...