Relationship Between Colchine Plasma Level and Frequency of Familial Mediterranean Fever Attacks

Background Colchicine is the mainstay of Familial Mediterranean Fever (FMF) treatment that reduces the frequency of attacks and prevents amyloidosis in the majority of patients. Colchicine, despite its narrow therapeutic window, is a well-tolerated oral drug that is rapidly absorbed by the gastrointestinal tract. However not all patients respond to colchicine and the response is not universal at the same doses. Therefore some patients require higher doses of colchicine to suppress their attacks. Objectives To investigate the relationship between colchicine plasma level and clinical response to colchicine in FMF patients. Methods Forty FMF patients with normal renal and hepatic functions, receiving colchicine regularly (steady state dose for at least 3 months with good -compliance) were enrolled to study in a 6 month-period. Blood samples were collected 30 minutes before the next colchicine dose. Colchicine plasma levels have been measured by using the device consecutive high performance liquid chromatography-mass spectrometry (LCMS-MS). Internal standard was added to plasma and the solution was extracted with ether:dichlormethane. Organic phase was evaporated to dryness under nitrogen. The residue dissolved in methanol was injected into the system. Quantitation was based on monitoring precursor ion and product ion for colchicine m/z 400.2 u003e310.3, and for internal standart colchicine- d3 m/ z 403.3u003e359.2. The assay was linear for colchicine over the range of 0.25-8 ng/ ml, r 2 is 0.997. Results Of the 40 patients, 24 were receiving 1.5 mg/day and 16 were receiving 2 mg/day. The mean plasma colchicine concentration of the entire cohort was 1.097±0.42 ng/mL and was within the therapeutic range (0.5-3 ng/mL). The mean plasma colchicine concentrations of patients who were on 1.5 mg/day (1.05 ng/mL) and 2 mg/day (1.17 ng/mL) colchicine treatment were not significantly different ( P =0.40). Plasma colchicine concentrations were positively correlated with daily oral colchicine dose. Before colchicine treatment, the mean attack number was 24.9±3.2/year and t after colchicine treatment was 1.6±0.4/ year ( P P =0.43). Optimal clinical response (decrease in the frequency of attacks) was found at oral doses of 1.5-2 mg/day, corresponding to plasma levels of approximately 1.097±0.42 ng/ml. Conclusions These data indicate that colchicine plasma levels correlate with daily oral doses of colchicine. FMF patients receiving 1.5 mg/day and 2 mg/day colchicine doses have similar plasma colchicine concentrations and also similar decrease in attack frequency. To evaluate the role of colchicine metabolism and plasma concentrations on the different dose requirements for optimal suppresion of attacks and on the colchicine-refractory FMF, further data is currently being studied by our group. Disclosure of Interest None declared