The maximal tolerable intravenous dosage of pentoxifylline in AIDS patients does not inhibit lipopolysaccharide-stimulated tumor necrosis factor alpha production.
Tumor necrosis factor alpha (TNF-alpha) may be involved in the pathogenesis of metabolic and endocrine changes in HIV infection. Pentoxifylline (PTX) is able to suppress the production of TNF-alpha in vitro. The effect of two dosages of intravenously administered PTX on clinical symptoms and ex vivo LPS-stimulated TNF-alpha production was evaluated in six clinically stable AIDS patients in a saline-controlled study. PTX in a dosage of 1.5 mg/min was tolerated without side effects. PTX in a dosage of 2.1 mg/min resulted in intolerable nausea and necessitated termination of infusion after 30 min. The average plasma concentration of PTX after infusion of 1.5 mg/min for 6 hr was 510+/-56 ng/ml, which is considerably below the concentrations that have been reported to suppress TNF-alpha production in vitro. No effect of PTX infusion (1.5 mg/min) on LPS-stimulated TNF production ex vivo was found. Our conclusion is that the maximally tolerated i.v. dosage of PTX in AIDS patients is 1.5 mg/min. LPS-stimulated ex vivo TNF-alpha production, at the LPS concentrations tested, was not inhibited by the plasma concentration of PTX that could be achieved at this dosage.
Heijligenberg
R
R
Department of Endocrinology and Metabolism, Academic Hospital of Amsterdam University, The Netherlands.
Romijn
J A
JA
Ackermans
M
M
Endert
E
E
Timmer
J G
JG
Sauerwein
H P
HP
D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy* / Q000276:immunology*; D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D004361:Drug Tolerance; D006801:Humans; D066298:In Vitro Techniques; D007275:Injections, Intravenous; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced; D010431:Pentoxifylline / Q000008:administration & dosage* / Q000009:adverse effects; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
D019380:Anti-HIV Agents; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D010431:Pentoxifylline