Abstract
Recent reports have demonstrated improvement in the clinical status and hemoglobin levels with use of intravenous arginine butyrate in patients with homozygous β-thalassemia and sickle cell disease. To allow optimalization of therapy, we conducted pharmacokinetic studies in nine patients, five with sickle cell disease and four with β-thalassemia, treated with continuous intravenous infusion of arginine butyrate. The disappearance of the drug after discontinuation was characterized by a biphasic elimination with an initial rapid phase followed by a slower phase. Redistribution was noted in five of the patients after 11.2 ± 4.0 min. The short half life was the result of both rapid clearance rate of 93.6 ± 31.9 ml/kg/min and small Vc (0.21 ± 0.26 l/kg) and Vss (0.31 ± 0.37 l/kg). While preliminary results of the effectiveness of arginine butyrate are encouraging with a rise of γ-globin mRNA and F reticulocytes in some patients, the rapid elimination of this agent will probably limit its current use to administration by continuous infusion.
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