A novel tandem mass spectrometry (LC-MS/MS) bio-analytical method was developed and validated for the synchronized quantitation of FINGOLIMOD (FIN) and its active metabolite, FINGOLIMOD-phosphate (FPH), in human whole blood using a unified sample preparation protocol. This method was successfully applied in a bio-equivalence study comparing a 0.5 mg test capsule to the reference product, Gilenya™, in twenty-eight healthy male subjects under fasting conditions. The study employed a randomized, single-dose, two-period, two-treatment, two-sequence crossover design with a seven-week washout period. FIN and its internal standard (IS) were extracted using liquid-liquid extraction, while FPH was isolated from the residual blood via protein precipitation. Quantitative analysis of both analytes was performed using positive electrospray ionization in multiple reaction monitoring mode (+ESI-MRM), with ion transitions of m/z 388.2 → 255.3 (IS: 392.12 → 259.2) for FIN, and m/z 308.4 → 255.3 (IS: 312.4 → 259.3) for FPH. The method was validated over dynamic calibration ranges of 10-800 pg/mL for FIN and 50-5000 pg/mL for FPH, meeting all acceptance criteria of EMEA bioanalytical method validation guidelines. Pharmacokinetic parameters including Cmax and AUC0t were determined for both FIN and FPH and compared between the test and reference formulations. The results confirmed that both products are bio-equivalent.

Multiple sclerosis (MS) is a chronic auto-immune disease. Most therapeutic strategies for treatment of this disease direct immune modulation and control of inflammatory processes. First-line therapeutic agents showed moderate efficacy and frequent side-effects with moderate efficacy in trials. Their parental administration and limited longterm adherence restrict their efficacy compared with second-line therapies. FINGOLIMOD as a second-line therapeutic agent has been shown to reduce annualized relapse rate, risk of disability progression and inflammatory activity of relapsing MS. Safety and efficacy FTY720: Safety and e: cacy issues are the main metrics for judgment of drug efficacy. In this article, we focus on cardiovascular e; ects of FTY720 treatment. E; ect of FTY720 on rate and rhythm, impact of FTY720 on endothelial cells, its atheroprotective effects, its effects on cardiac transplantation outcomes, vascular complications of FTY720, e; ects of FTY720 on endocrine functions and interaction of FTY720 with cardioactive agents are explained in this review article.

Background: While many studies have previously focused on FINGOLIMOD’s effect on immunecells, the effect it has on circulating and local central nervous system platelets (Plts) has not yetbeen investigated. This study will elucidate what effects FINGOLIMOD treatment has on multiplesclerosis (MS) patients’ plasma Plt levels. In addition, it will propose possible reasoning for theseeffects and suggest further investigation into this topic.Methods: This quasi‑experimental study used patients from the Isfahan Multiple Sclerosis Societyto produce a subject pool of 80 patients, including 14 patients who ceased FINGOLIMOD use due tocomplications. The patients had their blood analyzed to determine Plt levels both 1‑month priorto FINGOLIMOD treatment and 1‑month after FINGOLIMOD treatment had been started.Results: The mean level of Plts before initiation of FINGOLIMOD therapy (Plt1) among these MSpatients was 256.53 ± 66.26. After 1‑month of FINGOLIMOD treatment, the Plt level yielded anaverage of 229.96 ± 49.67 (Plt2). This number is significantly lower than the average Plt countbefore treatment (P<0.01).Conclusions: MS patients taking oral FINGOLIMOD treatment may be at risk for side‑effects causedby low Plt levels. This may not be a factor for patients with higher or normal Plt levels. However, a patient with naturally low Plt levels may experience a drop below the normal level and be atrisk for excessive bleeding. In addition to these possible harmful side‑effects, the decreased Pltpopulation may pose positive effects for MS patients.

Background. Renal ischemia-reperfusion injury (IRI) is one of the inevitable complications of surgery. The evidence shows that FINGOLIMOD, with its anti-inflammatory effects, can play a protective role in renal IRI. The main aim of the present study was to investigate the role of FINGOLIMOD against renal IRI in the heart tissue. Methods. Twenty-four male Wistar rats (220±20g) were treated with a single dose of FINGOLIMOD (1mg/kg) by intraperitoneal injection before the induction of kidney IRI. At the end of the reperfusion period, the oxidative stress biomarker (malondialdehyde) and antioxidant biomarkers (catalase, superoxide dismutase, glutathione, glutathione peroxidase, and total antioxidant capacity) were evaluated in the heart tissue. Results. FINGOLIMOD pretreatment could increase cardiac glutathione enzyme activity in the FINGOLIMOD+IR group compared to the IR group, which was not statistically significant (P>0. 05). The level of total antioxidant capacity in the heart tissue was also significantly increased in the FINGOLIMOD+IR group in comparison to the IR group (P<0. 05). Conclusion. FINGOLIMOD was able to prevent oxidative stress damage in the heart caused by kidney IR induction by increasing the level of total antioxidant capacity of the heart tissue. It is suggested that future studies evaluate the effects of this drug in clinical trials. Practical Implications. The total antioxidant capacity of the heart, as a distant organ affected by kidney IRI, is increased following FINGOLIMOD pre-treatment.