RBA in Healthy Adults
Parameter
GLOPERBA, 0.6 mg
(0.12 mg/mL, 5 mL)
Fasted (N=34)
GLOPERBA, 0.6 mg
(0.12 mg/mL, 5 mL)
Fed (N=34)
Cmax (ng/mL) 2.16 (0.87) 1.68 (0.39)
AUC0-t (h∙ng/mL) 18.59 (4.64) 17.20 (4.23)
AUC0-inf (h∙ng/mL) 19.90 (4.74) 18.47 (4.29)
Tmax (h) (Min-Max) 1.00 (0.50: 2.00) 2.00 (1.00: 4.00)
t1/2 (h) 31.04 (5.99) 30.54 (5.22)
Distribution
The mean apparent volume of distribution(Vz/F) of GLOPERBA in healthy adults was approximately1420 L. Colchicine binding to serum protein is reported to be low (39%) primarily due to albuminregardless of concentration.
Colchicine crosses the placenta (plasma levels in the fetus are reported to be approximately 15% of thematernal concentration) [see Use in Specific Populations (8.1)]. Colchicine also distributes into breast milkat concentrations similar to those found in the maternal serum [see Use in Specific Populations (8.2)].
MetabolismIn vitro studies using human liver microsomes have shown that CYP3A4 is involved in the metabolism ofcolchicine to 2-O-demethylcolchicine (2-DMC) and 3-O-demethylcolchicine (3-DMC). Glucuronidation isalso believed to be a metabolic pathway for colchicine.
Elimination
The mean elimination half-life of GLOPERBA in healthy adults is 31 hours (± 6 hours). In a publishedstudy in healthy adults approximately 40 to 65% of a single 1-mg oral dose of colchicine was reported to berecovered unchanged in urine. Enterohepatic recirculation and biliary excretion are postulated to play a rolein colchicine elimination. Colchicine is also a substrate of P-gp, and P-gp efflux is postulated to play animportant role in colchicine disposition.
Specific Populations
There is no difference between men and women in the pharmacokinetic disposition of colchicine.
Pediatric Patients: Pharmacokinetics of colchicine were not eva luated in pediatric patients.
Geriatric Patients: Pharmacokinetics of GLOPERBA have not been determined in elderly patients. Apublished report described the pharmacokinetics of a 1-mg oral colchicine tablet dose in four elderly womencompared to six young healthy males. The mean age of the four elderly women was 83 years (range 75 to93), mean weight was 47 kg (38 to 61 kg) and mean creatinine clearance was 46 mL/minute (range 25 to75 mL/minute). Mean peak plasma levels and AUC of colchicine were two times higher in elderly subjectscompared to young healthy males. It is possible that the higher exposure in the elderly subjects was due todecreased renal function.
Patients with Renal Impairment: Pharmacokinetics of colchicine in patients with mild and moderate renalimpairment is not known. A published report described the disposition of colchicine (1 mg) in young adultmen and women patients who had end-stage renal disease requiring dialysis compared to patients withnormal renal function. Patients with end-stage renal disease had 75% lower colchicine clearance (0.17 vs.
0.73 L/hr/kg) and prolonged plasma elimination half-life (18.8 hours vs. 4.4 hours) as compared to subjectswith normal renal function [see Use in Specific Populations (8.6)].
Patients with Hepatic Impairment: Published reports on the pharmacokinetics of intravenous colchicine inpatients with severe chronic liver disease, as well as those with alcoholic or primary biliary cirrhosis, andnormal renal function suggest wide inter-patient variability. In some subjects with mild to moderatecirrhosis, the clearance of colchicine is sig |
