Pharmacokinetics / bioavailability of colchicine in healthy male volunteers

Abstract

In a randomized 2-way cross-over study with twelve healthy male volunteers, two colchicine preparations (tablets, A vs. oral solution, B) were tested. The preparations were administered as single doses of 1 mg; prior to and up to 72 h after medication blood samples were collected and the plasma colchicine concentrations determined. Additionally urine samples were collected at 0-2, 2-4, 4-6, 6-8, 8-10, 10-24, 24-48, 48-72 and 72-96 h intervals. The colchicine plasma and urine concentrations were determined by a newly developed and validated RIA method. The mean area under the plasma concentration-time curve (AUC-1, AUC-3) was calculated as 23.95 +/- 12.10 (AUC-1) and 26.73 +/- 12.75 (AUC-3) h.ng/ml after application of A and 28.01 +/- 14.74 (AUC-1) and 31.57 +/- 16.58 (AUC-3) h.ng/ml after application of B, respectively. Mean peak plasma concentrations of 4.15 +/- 2.35 (A) and 4.88 +/- 3.90 (B) ng/ml were reached at 1.15 +/- 0.38 (A) and 1.13 +/- 0.42 (B) h after application. The mean terminal half-lives accounted for 9.31 +/- 3.98 (A) and 10.57 +/- 5.53 (B) h. The mean total clearance (Cl/F) and volume of distribution (V/F) were found to be 40.12 +/- 20.87 (A) and 46.58 +/- 24.65 (B) l/h and 472.59 +/- 196.46 (A) and 624.89 +/- 304.09 (B) l, respectively. The mean total amount excreted in urine (Ae) was 172.66 +/- 91.51 (A) and 174.85 +/- 63.53 (B) micrograms.(ABSTRACT TRUNCATED AT 250 WORDS)

Rapid and sensitive liquid chromatography–tandem mass spectrometry method for the quantitation of colchicine in human plasma

“…The mean maximum concentration (C max ) was 6.0 ± 3.4 ng/ml occurring at (t max ) 1.6 ± 0.7 h. The mean plasma elimination half-life was 16.5 ± 4.1 h and the mean area under the plasma concentration-time curve 44.1 ± 18.9 ng h/ml. The C max and t max values were similar to those reported in literature [14,15].…”

“…was infused into the mass spectrometer using a syringe pump. Optimized parameters were as follows: curtain gas, gas 1 and gas 2 (nitrogen) 15 …”

Pharmacokinetics and absolute bioavailability of colchicine after i. v. and oral administration in healthy human volunteers and elderly subjects

“…The latent period of absorption ranged from 10 to 15 min in the two groups, corresponding to the lag-time found by Thomas et al [12] of about 10 min in nine healthy male volunteers. Maximal plasma concentrations found in our study for healthy volunteers are in good agreement with those determined by Achtert et al [18] for the same oral dose in 12 healthy volunteers [4.15 (2.35) ng.ml-1]. Therefore, higher peak plasma colchicine concentrations were observed in elderly subjects despite the absolute bioavailability of colchicine in tablet form being about 45 % in both groups.…”

Colchicine‐Containing Plants

“…17 Analysis of toxicokinetics data during colchicine poisoning indicates that the ingestion of large amounts of colchicine does not delay gastrointestinal absorption. The absorption of colchicine from the gastrointestinal tract is rapid with peak plasma concentrations occurring about 1 -1.5 hours after administration.…”

“…17 Renal clearance increases moderately in patients ingesting large doses of colchicine. 17 Renal clearance increases moderately in patients ingesting large doses of colchicine.…”