Add time:09/03/2019         Source:sciencedirect.com

Decreased enzymatic production of cysteine in premature and newborn infants may limit the synthesis of glutathione. Unfortunately, cysteine supplementation is limited by associated toxicity and product instability. Procysteine™ (l-2-oxothiazolidine-4-carboxylate) is a prodrug of cysteine that is inert until metabolized to cysteine intracellulary, thus stimulating glutathione synthesis. The potential toxicities of cysteine and Procysteine™ were compared in two studies with neonatal rats (10 per group; 3 ± 1 days of age) after a single intravenous administration. In one study, acute high dosage survivorship was compared for approximately equimolar cysteine dosages of l-cysteine and Procysteine™. Mortality at 7 days after single intravenous dosages of l-cysteine at 1.52 or 1.14 g/kg or Procysteine™ at 1.80 or 1.35 g/kg was 80, 50, 10 and 0%, respectively. Clinical pathology parameters and body and organ weights were compared in a second study, following a moderate dosage of Procysteine™ or equimolar or lower dosages of lcysteine. No differences were observed in clinical pathology parameters nor body or organ weights at 14 days following single intravenous dosages of l-cysteine at 369, 185 or 37 mg/kg or Procysteine™ at 450 mg/kg. Also, Procysteine™ solutions were considerably more stable than l-cysteme solutions (months vs. hours, respectively). These studies indicated that cysteine supplementation in infants may be enhanced by Procysteine™ administration.

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