Oral absorption characteristics and pharmacokinetics of colchicine in healthy volunteers after single and multiple doses

J Clin Pharmacol. 1996 Oct;36(10):874-83. doi: 10.1002/j.1552-4604.1996.tb04753.x.

Abstract

Colchicine is an antimitotic drug used to treat gout and familial Mediterranean fever. Absolute bioavailability, pharmacokinetics, and absorption characteristics of colchicine after single 1.0-mg doses in oral solution or tablet form or 0.5-mg intravenous doses were compared in 6 subjects. This study was combined with 14 days of multiple-dose administration of 1.0-mg colchicine tablets in 6 subjects. Serial blood samples were collected for 48 hours after administration of single doses and for 120 hours after the last dose in the multiple-dose regimen. Plasma colchicine profiles as measured by radioimmunoassay were analyzed using deconvolution and compartmental methods. After intravenous bolus injection of colchicine, the area under the concentration-time curve (AUC) was 61.2 +/- 12.7 ng.hr/mL, steady-state volume of distribution (Vss) was 419 +/- 95 L, systemic clearance (Cl) was 8.5 +/- 1.8 L/hr, and the terminal half-life (t1/2) was 57.8 +/- 10.7 hours. After oral administration in solution form, peak plasma concentrations (Cmax) of 6.50 +/- 1.03 ng/mL were reached at time (tmax) 1.07 +/- 0.55 hours, with a rate of 0.109 +/- 0.024 hr-1 (Cmax/AUC); bioavailability was 47 +/- 14%. Oral tablets yielded similar Cmax, tmax, and Cmax/AUC values, but AUC was significantly lower. Most participants exhibited a secondary peak within 6 hours of administration, possibly in relation to a second absorption site or enterohepatic recirculation. This second absorption process was significantly longer than the first one, and accounted for a similar amount of colchicine absorbed. From the multiple-dose study, a model including an alteration of colchicine absorption due to possible drug-induced gastrointestinal modifications allowed better determination of steady-state plasma concentrations of colchicine.

Publication types

  • Comparative Study

MeSH terms

  • Absorption
  • Administration, Oral
  • Adult
  • Biological Availability
  • Colchicine / administration & dosage
  • Colchicine / blood
  • Colchicine / pharmacokinetics*
  • Gout Suppressants / administration & dosage
  • Gout Suppressants / blood
  • Gout Suppressants / pharmacokinetics*
  • Half-Life
  • Humans
  • Male
  • Middle Aged
  • Radioimmunoassay
  • Solutions
  • Statistics, Nonparametric
  • Tablets

Substances

  • Gout Suppressants
  • Solutions
  • Tablets
  • Colchicine