The in vitro effect of chloramphenicol (CAP) on ferrochelatase (heme synthetase) activity was tested on bone marrow obtained from patients with and without evidence of CAP toxicity. In the control group of 24 randomly selected patients who had not previously received CAP, inhibition of heme synthesis by CAP (30 μ g/ml) was found in 2 and stimulation in 4 instances. In the majority, i.e. 18 patients, heme synthesis was not influenced by CAP. Studies on bone marrow obtained from 8 patients who tolerated CAP without adverse effects revealed stimulation of heme synthesis in 2 instances and inhibition in none. Transient inhibition of ferrochelatase was found in only 1 out of 4 patients recovering from aplastic anemia caused by CAP. However, inhibition of ferrochelatase was repeatedly observed in samples obtained from 3 out of 5 patients with reversible, sideroblastic anemia due to CAP. The intensity and incidence of in vitro alterations of heme synthesis by CAP increased at higher CAP concentrations (300 μ g/ml). We conclude that a direct, dose-dependent interference of CAP with ferrochelatase may inhibit heme synthesis in vitro and erythroid iron utilization in susceptible individuals.

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