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MODEL‐INDEPENDENT PHARMACOKINETICS OF COLCHICINE AFTER ORAL ADMINISTRATION TO HEALTHY VOLUNTEERS
Author(s) -
GIRRE C.,
THOMAS G.,
SCHERRMANN J.M.,
CROUZETTE J.,
FOURNIER P.E.
Publication year - 1989
Publication title -
fundamental and clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.655
H-Index - 73
eISSN - 1472-8206
pISSN - 0767-3981
DOI - 10.1111/j.1472-8206.1989.tb00688.x
Subject(s) - pharmacokinetics , colchicine , oral administration , volume of distribution , urine , ingestion , medicine , half life , pharmacology , distribution (mathematics) , chemistry , mathematics , mathematical analysis
Summary— 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 t 1/2β , AUC, MRT, CI T /F, CI R , V d 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.