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A Phase I/II Evaluation of Oral L‐2‐Oxothiazolidine‐4‐Carboxylic Acid in Asymptomatic Patients Infected with Human Immunodeficiency Virus
Author(s) -
BarditchCrovo Patricia,
Noe Dennis,
Skowron Gail,
Lederman Michael,
Kalayjian Robert C.,
Borum Peggy,
Buier Rose,
Rowe W. Bruce,
Goldberg Dennis,
Lietman Paul
Publication year - 1998
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1002/j.1552-4604.1998.tb04435.x
Subject(s) - asymptomatic , prodrug , placebo , pharmacokinetics , dose , pharmacology , peripheral blood mononuclear cell , medicine , oral administration , whole blood , bioavailability , glutathione , pharmacodynamics , chemistry , gastroenterology , in vitro , biochemistry , pathology , alternative medicine , enzyme
A randomized double‐blind, placebo‐controlled study was conducted in 37 asymptomatic HIV‐infected individuals (mean CD4 count 707 cells/mm 3 ) to characterize the safety, pharmacokinetics, and effect on blood thiols of three dosage levels of a cysteine prodrug, L‐2‐oxothiazolidine‐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 administration three times daily, a statistically significant increase was seen 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 blood cysteine and peripheral blood mononuclear cell (PBMC) glutathione was not seen during the study period.