Safety, tolerability, and pharmacokinetic effects of thalidomide in patients infected with human immunodeficiency virus: AIDS Clinical Trials Group 267.
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.
Wohl
David A
DA
Division of Infectious Diseases, University of North Carolina, Chapel Hill, NC 27599, USA. wohl@med.unc.edu
Aweeka
Francesca T
FT
Schmitz
John
J
Pomerantz
Roger
R
Cherng
Deborah Weng
DW
Spritzler
John
J
Fox
Lawrence
L
Simpson
David
D
Bell
Dawn
D
Holohan
M K
MK
Thomas
Steven
S
Robinson
Wayne
W
Kaplan
Gilla
G
Teppler
Hedy
H
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
D019380:Anti-HIV Agents; D013792:Thalidomide