title: Safety, tolerability, and pharmacokinetic effects of thalidomide in patients infected with human immunodeficiency virus: AIDS Clinical Trials Group 267.
abstract: Thalidomide is used to treat human immunodeficiency virus (HIV)-associated conditions, including aphthous ulcers and wasting syndrome. The safety, tolerability, and pharmacokinetics of a formulation of thalidomide with improved bioavailability in HIV-infected persons was examined in a placebo-controlled, dose-escalating phase 1 study. Subjects with CD4 cell counts of 200-500 cells/mm(3) were enrolled and randomized 3:1 in groups of 12 to receive 50, 100, or 150 mg of thalidomide or matching placebo. Two subjects who received 150 mg of drug and 2 subjects assigned placebo experienced dose-limiting toxicity. Concentrations of thalidomide in the blood increased with escalating dose, but the time to maximum concentration and clearance did not differ across dose cohorts. Previous suggestions of autoinduction of drug metabolism were not confirmed by this study. At the doses studied, thalidomide was tolerated well and had linear pharmacokinetics.
authors: Division of Infectious Diseases, University of North Carolina, Chapel Hill, NC 27599, USA. wohl@med.unc.edu
authors: David A
authors: DA
authors: Wohl
authors: Francesca T
authors: FT
authors: Aweeka
authors: John
authors: J
authors: Schmitz
authors: Roger
authors: R
authors: Pomerantz
authors: Deborah Weng
authors: DW
authors: Cherng
authors: John
authors: J
authors: Spritzler
authors: Lawrence
authors: L
authors: Fox
authors: David
authors: D
authors: Simpson
authors: Dawn
authors: D
authors: Bell
authors: M K
authors: MK
authors: Holohan
authors: Steven
authors: S
authors: Thomas
authors: Wayne
authors: W
authors: Robinson
authors: Gilla
authors: G
authors: Kaplan
authors: Hedy
authors: H
authors: Teppler
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000009:adverse effects*; D018791:CD4 Lymphocyte Count; D004311:Double-Blind Method; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D008297:Male; D016032:Randomized Controlled Trials as Topic; D013792:Thalidomide / Q000009:adverse effects* / Q000493:pharmacokinetics
chemical_list: D019380:Anti-HIV Agents; D013792:Thalidomide