A phase I/II evaluation of oral L-2-oxothiazolidine-4-carboxylic acid in asymptomatic patients infected with human immunodeficiency virus.
A randomized double-blind, placebo-controlled study was conducted in 37 asymptomatic HIV-infected individuals (mean CD4 count 707 cells/mm3) 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.
Barditch-Crovo
P
P
Department of Medicine, The Johns Hopkins School of Medicine, Baltimore, Maryland, USA.
Noe
D
D
Skowron
G
G
Lederman
M
M
Kalayjian
R C
RC
Borum
P
P
Buier
R
R
Rowe
W B
WB
Goldberg
D
D
Lietman
P
P
D000328:Adult; D019380:Anti-HIV Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D003545:Cysteine / Q000097:blood; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005978:Glutathione / Q000097:blood; D015658:HIV Infections / Q000097:blood* / Q000188:drug therapy; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008875:Middle Aged; D011355:Prodrugs / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D011761:Pyrrolidonecarboxylic Acid; D013844:Thiazoles / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D053778:Thiazolidines
D019380:Anti-HIV Agents; D011355:Prodrugs; D013844:Thiazoles; D053778:Thiazolidines; D005978:Glutathione; D003545:Cysteine; D011761:Pyrrolidonecarboxylic Acid; C029536:2-oxothiazolidine-4-carboxylic acid