Simultaneous succinylacetone-nitisinone measurement in tyrosinemia type I patients and evaluation of the nitisinone therapeutic range

AUTHORS

ABSTRACT

Introduction: in tyrosinemia type I (HT1) accumulation of succinylacetone causes severe hepatic and renal dysfunction and hepatocellular carcinoma; the only drug used for the treatment is nitisinone (NTBC). While succinylacetone measurement from dried blood spots (DBS) is used for the diagnosis, simultaneous measurements of succinylacetone and NTBC are preferred in the treatment follow-up. The aim of this study was to evaluate the results of simultaneous LC-MS/MS determination of succinylacetone and NTBC in HT1 patients. The plasma/DBS ratio and the therapeutic range for NTBC were also determined.
Methods: plasma and DBS samples from HT1 patients were used for succinylacetone and NTBC analyses and LC-MS/MS was used for simultaneous measurements of both parameters.
Results: the plasma/DBS ratio for NTBC was 1.92. The succinylacetone level, which was determined as the treatment goal, was suppressed (<1 µmol/L) with the use of NTBC in 88.6% (101/114) of the cases. However, DBS NTBC level was found above the therapeutic upper limit in 65.8% of these cases.
Conclusion: the suppression rate of succinylacetone, which is one of the treatment targets for HT1, is high (88.6%). However, the recommended therapeutic upper limit for NTBC was exceeded in 65.8% of the patients. It is also important to calculate the plasma/DBS NTBC ratio in laboratories analysing NTBC from DBS and to evaluate the therapeutic range targets according to this ratio. Establishing an individualized dose with a review of the therapeutic target may be considered in longitudinal studies examining clinical outcomes

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