A PHASE I II EVALUATION OF ORAL L-2-OXOTHIAZOLIDINE-4-CARBOXYLIC ACIDIN ASYMPTOMATIC PATIENTS INFECTED WITH HUMAN-IMMUNODEFICIENCY-VIRUS/

A randomized double-blind, placebo-controlled study was conducted in 3 7 asymptomatic HIV-infected individuals (mean CD4 count 707 cells/mm(3 )) to characterize the safety, pharmacokinetics, and effect on blood t hiols of three dosage levels of a cysteine prodrug, L-2-oxothiazolidin e-4-carboxylic acid (OTC; Procysteine; Clintec Technologies, Deerfield , IL). Single-dose administration of OTC resulted in measurable plasma levels at all dosages, with a mean peak plasma concentration of 734 /- 234 nmol/mL at the highest dosage studied. After 4 weeks of adminis tration three times daily, a statistically significant increase was se en in whole blood glutathione in the 1,500 mg and 3,000 mg dose groups compared with the placebo group. A significant increase in whole bloo d cysteine and peripheral blood mononuclear cell (PBMC) glutathione wa s not seen during the study period. (C)1998 The American College of Cl inical Pharmacology.