ఫార్మాస్యూటికా అనలిటికా ఆక్టా

నైరూప్య

Urinary Excretion Levels of MMX-Mesalazine as a Tool to Assess Non-Adherence

Tessa EH Romkens, Jody Salomon, Wilbert HM Peters, David M Burger, Frank Hoentjen and Joost PH Drenth

Objective: 5-Amino salicylicacid (5-ASA) is the cornerstone of ulcerative colitis treatment, with (assessment of) non-adherence as a challenge. Multi-matrix release (MMX)-mesalazine has the advantage of once-daily (OD) dosing. Primarily we assessed urinary (NAc-) 5-ASA excretion, as measured by High-Performance Liquid Chromatography (HPLC), in order to monitor nonadherence, in healthy volunteers taking MMX-mesalazine. Secondly, we established urinary (NAc-)5-ASA cut-off levels for (partial) nonadherence. Method: We studied 25 healthy adult volunteers who used MMX-mesalazine 2400 mg OD (days 1-4), followed by 1200 mg twice daily (BID) (days 8-11), separated by a drug-free interval of 3 days. Daily morning urine spot samples were collected. The cut-off level for adherence was set at the lowest steady state (NAc-)5-ASA urinary concentration level. Results: Stability of urinary 5-ASA and NAc-5-ASA, stored at room temperature during 24 hours was 96.4 ± 8.3% and 96.4 ± 4.1%. Recovery of urinary 5-ASA and NAc-5-ASA was 114.3 ± 10.4% and 107.5 ± 6.4%. The limit of detection and quantification were 1.1 ug/ml and 3.5 ug/ml for NAc-5-ASA and 0.4 ug/ml and 1.3 ug/ml for 5-ASA. The maximal 5-ASA within-run and between-run relative SD were 10.4% and 12.5%. The cut-off level for non-adherence was determined at 9.67 (OD) and at 15.39 (BID) mg/mmol (NAc-) 5-ASA per mmol creatinine. Conclusion: HPLC is a feasible, sensitive and reproducible method to measure urinary (NAc-) 5-ASA excretion in volunteers taking MMX-mesalazine. This study establishes urinary (NAc-) 5-ASA cut-off levels for MMX-mesalazine non-adherence that may be useful in clinical practice and future trials.