title: Model-independent pharmacokinetics of colchicine after oral administration to healthy volunteers.
abstract: The pharmacokinetics of colchicine were studied after oral administration of three doses (0.5, 1.0 and 1.5 mg) to nine healthy male volunteers according to randomized cross-over design. Plasma and urine samples were collected during 48 h after ingestion, and assayed for colchicine levels by a specific and highly sensitive radio-immunoassay. Pharmacokinetic parameters t1/2 beta, AUC, MRT, CIT/F, CIR, Vd area/F) were calculated by model-independent methods and compared across doses by multiway analysis of variance. Terminal half-life (15.5-19.2 h), mean residence time (15.7-20.3 h), oral systemic (32.2-40.3 l/h) and renal (3.9-4.7 l/h) clearances, and oral volume of distribution (11.4-14.9 l/kg) did not differ significantly between doses, whereas the area under the concentration-time curve was proportional to dose. Our results show that: 1. within the dose range studied (0.5-1.5 mg), the pharmacokinetics of colchicine are linear; 2. monitoring colchicine levels up to 48 hours yields much larger estimates of terminal half-life and volume of distribution than previously reported from considerably shorter studies.
authors.affiliation: Unité de Pharmacologie Clinique, Hôpital Fernand Widal, Paris, France.
authors.forename: C
authors.initials: C
authors.lastname: Girre
authors.forename: G
authors.initials: G
authors.lastname: Thomas
authors.forename: J M
authors.initials: JM
authors.lastname: Scherrmann
authors.forename: J
authors.initials: J
authors.lastname: Crouzette
authors.forename: P E
authors.initials: PE
authors.lastname: Fournier
mesh_terms: D000284:Administration, Oral; D000328:Adult; D003078:Colchicine / Q000008:administration & dosage / Q000493:pharmacokinetics*; D006207:Half-Life; D006801:Humans; D008297:Male; D008954:Models, Biological
chemical_list: D003078:Colchicine