title: Colchicine disposition in human leukocytes after single and multiple oral administration.
abstract: Inasmuch as leukocytes were reported to be an active pharmacologic compartment, colchicine disposition was determined in plasma, granulocytes, and mononuclear cells in healthy volunteers after 1 mg oral single and multiple doses. After the single dose, maximal colchicine concentration was observed at 1 hour in plasma and 47 hours later in leukocytes. This delay was confirmed by the slow accumulation of colchicine by lymphocytes in culture. In the multiple-dose study, mean granulocyte colchicine concentration (20 to 53 ng/10(9) cells) were twofold higher than in mononuclear cells (9 to 24 ng/10(9) cells). Mean predicted colchicine multiple-dose granulocyte and mononuclear cell concentrations were 2.5-fold and ninefold higher, respectively, than those measured. After the last dose, colchicine decreased, with half-life values between 41 and 46 hours for leukocytes and 49 hours for plasma. This study validates leukocytes as a microcompartment whose kinetics correlates with colchicine biologic effects.
authors.affiliation: INSERM U26, Hôpital Fernand Widal, Paris, France.
authors.forename: O N
authors.initials: ON
authors.lastname: Chappey
authors.forename: E
authors.initials: E
authors.lastname: Niel
authors.forename: J L
authors.initials: JL
authors.lastname: Wautier
authors.forename: P P
authors.initials: PP
authors.lastname: Hung
authors.forename: M
authors.initials: M
authors.lastname: Dervichian
authors.forename: D
authors.initials: D
authors.lastname: Cattan
authors.forename: J M
authors.initials: JM
authors.lastname: Scherrmann
mesh_terms: D000284:Administration, Oral; D000328:Adult; D002478:Cells, Cultured; D003078:Colchicine / Q000008:administration & dosage / Q000097:blood*; D006098:Granulocytes / Q000378:metabolism; D006207:Half-Life; D006801:Humans; D007962:Leukocytes / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008214:Lymphocytes / Q000378:metabolism; D008297:Male; D008875:Middle Aged
chemical_list: D003078:Colchicine