Pharmacokinetics considerations for gout treatments

Abstract

Colchicine is a drug with a narrow therapeutic-toxicity window. Co-prescription with strong CYP3A4 or P-glycoprotein inhibitors can greatly modify its pharmacokinetics and is to be avoided. Elimination of canakinumab mainly occurs via intracellular catabolism, following receptor mediator endocytosis. Canakinumab appears to be a good alternative for patients with contraindications to colchicine, NSAIDs and corticosteroids. For patients with renal impairment, some authors recommend that the allopurinol maximum dosage should be adjusted to creatinine clearance. If the urate target cannot be achieved, the therapy should be switched to febuxostat, which is appropriate with mild-to-moderate renal failure. Anti-pegloticase antibodies affect the pharmacokinetics of the drug because they increase its clearance, with loss of pegloticase activity.

Consensus Statement Regarding the Efficacy and Safety of Long-Term Low-Dose Colchicine in Gout and Cardiovascular Disease

“…The major source of colchicine pharmacokinetic variance is oral bioavailability, which ranges from 16% to 53% in healthy individuals 10 and reflects both transport and metabolism within the enterocyte. P-glycoprotein (P-gp), also known as multidrug resistance protein (MDR1) or ATP-binding cassette subfamily B member 1 (ABCB1) acts at the site of absorption to secrete colchicine via efflux transport back into the intestinal lumen and plays a similar role in the biliary ductules of the liver and proximal tubule of the kidney.…”

A wild rice-derived peptide R14 ameliorates monosodium urate crystals-induced IL-1β secretion through inhibition of NF-κB signaling and NLRP3 inflammasome activation

“…Although colchicine is a widely used and recommended first line therapy for the treament of gout, undesirable adverse effects have however been reported, including severe diarrhea, vomiting and nausea ( Slobodnick et al, 2018 ; Stewart et al, 2020 ). Additionally, long-term use of colchicine may also lead to serious adverse effects such as renal impairment, myopathy, and rhabdomyolysis ( Fernández-Cuadros et al, 2019 ; Richette, Frazier & Bardin, 2014 ). The fact that the R14 peptide exhibited no hemolytic activity toward normal erythrocytes, this suggested the very low toxicity to the mammalian cells and would surpass the limitation for development of this peptide as future therapeutics.…”

Association Between the Risk of Hyperuricemia and Changes in Branched-Chain Amino Acids Intake Over Twelve Years: A Latent Class Trajectory Analysis From the China Health and Nutrition Survey, 1997–2009

“…The pooled prevalence of HU was 13.3% in mainland China from 2000 to 2014 ( 2 ). HU is considered a risk factor for gout ( 3 ), cardiovascular disease ( 4 ), stroke ( 5 ), diabetes ( 6 ), and hypertension ( 7 ). HU is becoming a great health issue and is arousing more attention.…”