Toxicity, Biological Activity, and Pharmacokinetics of TXU (Anti-CD7)-Pokeweed Antiviral Protein in Chimpanzees and Adult Patients Infected with Human Immunodeficiency Virus

• Published in: The Journal of pharmacology and experimental therapeutics 1999-12, Vol.291 (3), p.1301-1307
• Main Authors: Fatih M. Uckun, Kelly Bellomy, Karen O'Neill, Yoav Messinger, Trista Johnson, Chun-Lin Chen
• Format: Article
• Language: English
• Subjects: Adult; Animals; Anti-HIV Agents - administration & dosage; Anti-HIV Agents - pharmacokinetics; Anti-HIV Agents - therapeutic use; Area Under Curve; CD4-CD8 Ratio - drug effects; CD56 Antigen - immunology; Female; Follow-Up Studies; Half-Life; HIV Infections - blood; HIV Infections - drug therapy; HIV Infections - virology; HIV-1 - drug effects; Humans; Immunoconjugates - administration & dosage; Immunoconjugates - pharmacokinetics; Immunoconjugates - therapeutic use; Male; Middle Aged; Pan troglodytes; Plant Proteins - administration & dosage; Plant Proteins - pharmacokinetics; Plant Proteins - therapeutic use; Ribosome Inactivating Proteins, Type 1; Viral Load; Virus Replication - drug effects
• ISSN: 0022-3565; 1521-0103
• DOI: 10.1016/S0022-3565(24)35240-1

The purpose of the present study was to evaluate the toxicity and pharmacokinetics of TXU (anti-CD7)-pokeweed antiviral protein (PAP) in human immunodeficiency virus (HIV)-infected chimpanzees and adult patients. At a total dose of 100 μg/kg, TXU-PAP did not cause severe (grade ≥ 3) toxicity in any of the four HIV type 1 (HIV-1)-infected or two healthy chimpanzees. The only side effects were a transient elevation of the liver enzyme alanine aminotransferase between days 2 and 14 without a concomitant rise in total bilirubin levels and a decrease in the serum albumin levels between days 1 and 5 without any concomitant weight gain or peripheral edema. TXU-PAP showed favorable pharmacokinetics in chimpanzees with a plasma elimination half-life of 5.1 to 12.0 h and a systemic clearance of 5.8 to 15.1 ml/h/kg. At 2 months after initiation of the TXU-PAP infusions, the HIV-1 burden was reduced to below-detection levels in three of the four chimpanzees, and in the remaining chimpanzee, the HIV burden was