A Pharmacokinetic Study of Colchicine With an Oral Contraceptive

• Maximum Plasma Concentration of Norethindrone With Colchicine at Steady State (Cmax, ss) [ Time Frame: Day 21 of each cycle - plasma concentrations were drawn prior to the morning dose (0 hour) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 (prior to pm colchicine/placebo dose), and 24 hours post-dose. ] [ Designated as safety issue: No ]
  
• Maximum Plasma Concentration of Norethindrone With Placebo at Steady State (Cmax, ss) [ Time Frame: Day 21 of each cycle - plasma concentrations were drawn prior to the morning dose (0 hour) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 (prior to pm colchicine/placebo dose), and 24 hours post-dose. ] [ Designated as safety issue: No ]
  
• Maximum Plasma Concentration of Ethinyl Estradiol With Colchicine at Steady State (Cmax, ss) [ Time Frame: Day 21 of each cycle - plasma concentrations were drawn prior to the morning dose (0 hour) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 (prior to pm colchicine/placebo dose), and 24 hours post-dose. ] [ Designated as safety issue: No ]
  
• Maximum Plasma Concentration of Ethinyl Estradiol With Placebo at Steady State (Cmax, ss) [ Time Frame: Day 21 of each cycle - plasma concentrations were drawn prior to the morning dose (0 hour) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 (prior to pm colchicine/placebo dose), and 24 hours post-dose. ] [ Designated as safety issue: No ]
  
• Maximum Plasma Concentration of Colchicine With Norethindrone/Ethinyl Estradiol at Steady State (Cmax, ss) [ Time Frame: Day 21 of each cycle - plasma concentrations were drawn prior to the morning dose (0 hour) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 (prior to pm colchicine/placebo dose), and 24 hours post-dose ] [ Designated as safety issue: No ]
  
• Area Under the Concentration Versus Time Curve From Time 0 to Time t [AUC(0-t)] for Norethindrone With Colchicine [ Time Frame: Day 21 of each cycle - plasma concentrations were drawn prior to the morning dose (0 hour) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 (prior to pm colchicine/placebo dose), and 24 hours post-dose. ] [ Designated as safety issue: No ]
  
• Area Under the Concentration Versus Time Curve From Time 0 to Time t [AUC(0-t)] for Norethindrone With Placebo [ Time Frame: Day 21 of each cycle - plasma concentrations were drawn prior to the morning dose (0 hour) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 (prior to pm colchicine/placebo dose), and 24 hours post-dose. ] [ Designated as safety issue: No ]
  
• Area Under the Concentration Versus Time Curve From Time 0 to Time t [AUC(0-t)] Ethinyl Estradiol With Colchicine [ Time Frame: serial pharmacokinetic plasma concentrations were drawn prior to dose administration (0 hour) and at 0.33, 0.67, 1, 1.33, 1.67, 2, 2.33, 2.67, 3, 3.33, 3.67, 4, 4.5, 5, 5.5, 6, 7, 8, 10, 14, 18, 24, 36, and 48 hours after drug administration. ] [ Designated as safety issue: No ]
  
• Area Under the Concentration Versus Time Curve From Time 0 to Time t [AUC(0-t)] for Ethinyl Estradiol With Placebo [ Time Frame: Day 21 of each cycle - plasma concentrations were drawn prior to the morning dose (0 hour) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 (prior to pm colchicine/placebo dose), and 24 hours post-dose. ] [ Designated as safety issue: No ]
  
• Area Under the Concentration Versus Time Curve From Time 0 to Time t [AUC(0-t)] for Colchicine With Norethindrone/Ethinyl Estradiol [ Time Frame: Day 21 of each cycle - plasma concentrations were drawn prior to the morning dose (0 hour) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 (prior to pm colchicine/placebo dose), and 24 hours post-dose ] [ Designated as safety issue: No ]
  

This study will evaluate the effect, if any, of twice daily dosing of colchicine 0.6 mg at steady state on the steady state pharmacokinetic profile of ethinyl estradiol and norethindrone (Ortho-Novum 1/35). It will also evaluate the effects, if any, of steady state ethinyl estradiol and norethindrone on colchicine at steady state. Finally, this study will assess the safety and tolerability of concurrent use of colchicine and an estrogen/progesterone-containing oral contraceptive. Following an optional single cycle run-in period in which subjects taking other oral contraceptives are switched to Ortho-Novum 1/35, 30 healthy adult female volunteers of child bearing age (18-45 years old) will be randomized in a double blind crossover fashion to receive each of two ethinyl estradiol and norethindrone dosing regimens in sequence. During each of the two dosing periods, subjects will receive one ethinyl estradiol and norethindrone tablet on the mornings of Days 1-7 of their cycles. On days 8-21, subjects will receive twice daily doses of either colchicine (0.6 mg capsule twice daily with breakfast and dinner) or the placebo (one capsule twice daily with breakfast and dinner), according to their randomization schedule, along with one ethinyl estradiol and norethindrone tablet. Subjects will receive the alternate dosing regimen in Cycle 2. Blood samples will be drawn at times sufficient to determine the steady state pharmacokinetics of ethinyl estradiol and norethindrone with and without steady state colchicine. In addition, during the cycle in which active colchicine is given, the effect of steady state ethinyl estradiol and norethindrone on steady state colchicine will be evaluated. Subjects will be monitored for adverse effects throughout the study via query and spontaneous reporting. Additionally baseline 12 lead EKG and vital signs will be compared to those obtained at time points throughout the study period.