Background/Purpose: Patients receiving colchicine for prophylaxis of gout flares are at risk for dose-related gastrointestinal toxicity (nausea, vomiting, diarrhea, abdominal pain) if they have pre-existing renal impairment. A published pharmacokinetic study showed that exposure to colchicine (Cmax and AUC) was increased by 1.5 and 2-fold, and the systemic clearance (CL/F) was decreased by 0.5 and 0.4-fold respectively, in patients with moderate and severe renal impairment (eGFR 30-59 mL/min/1.73 m² and 15-29 mL/min/1.73 m², respectively). It is therefore valuable to determine appropriate dosing regimens for various degrees of kidney dysfunction that will maintain colchicine levels within the known narrow therapeutic index of 0.5–3 ng/mL.

Methods: Data from a pharmacokinetic study  with  colchicine oral solution in healthy subjects was used to construct a pharmacokinetic model.  Using the derived pharmacokinetic disposition parameters, simulation of colchicine plasma concentrations was undertaken for various levels of renal impairment for dosing with colchicine oral solution.

Results: When administered the standard colchicine 0.6 mg dose daily, therapeutic levels can be expected to be maintained in patients with mild renal impairment, defined as estimated glomerular filtration rate (eGFR) of 60–89 ml/min/1.73 m². Among patients with moderate renal impairment, the optimal dosage is 0.48 mg (4 mL) of colchicine oral solution daily. Among patients with severe renal impairment, the recommended dosage is 0.3 mg (2.5 mL) of colchicine oral solution daily. No dosage adjustment is expected to be needed for patients with mild renal impairment.  However, without dosage reduction, patients with moderate and severe renal impairment would have excursions to toxic levels for 5% and 16% of the dosing interval, respectively. Administering a lower dose such as 0.3 mg daily, by splitting the conventional 0.6 mg tablet could result in plasma colchicine levels in subtherapeutic range towards the end of dosing interval.  

Conclusion: Colchicine oral solution (0.12 mg/mL) offers  a convenient option for appropriate dosing in patients with moderate to severe renal impairment or with concurrent use of most interacting medications.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/prophylaxis-of-gout-flares-in-patients-with-renal-impairment-dosing-adjustments-with-colchicine-oral-solution-informed-by-a-pharmacokinetic-model/