Bone marrow depression thiamphenicol

However, the use of CAP was soon restricted after its association with bone marrow depression and aplastic anemia. The underlying biochemical lesion is still obscure, and adequate animal models are lacking. Since thiamphenicol, a CAP analogue where the nitro function has been replaced by a MeSC>2 -group, has never been associated with aplastic anemia, Yunis and coworkers suggested that the p-n il.ro group of CAP may be involved in the development of aplastic anemia129,130. 

Thiamphenicol is a semi-synthetic derivative of chloramphenicol. It can cause reversible bone marrow depression, but fatal aplastic anemia has not been reported in humans. Oral bioavailability in pre-ruminant calves is 60%. It is somewhat less lipid- and somewhat more water-soluble than chloramphenicol and therefore crosses cell membranes less readily. Hepatic metabolism is limited, and elimination is primarily as parent drug in the urine. Limited published data indicate that it has a high distribution volume in ruminants. It has been used in feed in pigs and chickens, but such usage is now limited. 

Thiamphenicol can also be the cause of serious bone marrow damage (Keiser et al. 1972 Kaltwasser et al. 1974). The incidence of bone marrow depression, on the other hand, is lower, with an obvious dose dependence and reversibility (Beck 1975). Neurotoxicity, gastrointestinal disturbances, and alopecia are further adverse reactions to thiamphenicol (Manten 1975). 

Nine cases of bone marrow depression following the application of thiamphenicol have been observed in a hospital in France. In 5 of the patients the damage appeared to be reversible, but in 4 of them the neutropenia contributed to the fatal development of the infections (33 -). 

Thiamphenicol is a synthetic chloramphenicol analogue with a molecular structure that appears to preserve tlie antibacterial properties, decrease markedly the metabolism by the liver, enhance kidney excretion, and eliminate tlie occurrence of aplastic anemia, although it is probably more liable to cause dose-dependent reversible depression of the bone marrow (15). These properties make it preferable in certain cases to chloramphenicol (36, 37). 

---