Assessment of alteration in antiviral plasma concentration across dialysis days: computational and analytical study.

Aim: Protein-bound uremic toxins (PBUTs) may displace drugs from the plasma proteins and render them more liable to clearance. This study aims to investigate the possible interplay between PBUTs and directly acting antivirals (DAAs). Methods: PBUT plasma protein binding was compared to those of paritaprevir (PRT), ombitasivir (OMB) and ritonavir (RTV) in silico to assess the possible competitive displacement. The three drugs were LC-MS/MS determined in seven patients across dialysis and non-dialysis days and results were compared. Results & conclusion: Results showed that the PBUT exhibited a lower binding than DAA reducing the liability of their competitive displacement. This was echoed by an unaltered plasma concentration across dialysis days. Results may indicate that PBUT accumulation may have limited effect on disposition of DAA.

Development and Validation of a New LC-MS/MS Analytical Method for Direct-Acting Antivirals and Its Application in End-Stage Renal Disease Patients.

BACKGROUND AND OBJECTIVE: The effectiveness of direct-acting antivirals (DAAs) is not well established in end-stage renal disease (ESRD) patients. Assessment of the plasma concentrations may support understanding of their therapeutic outcomes in this population. The aim of this study is to develop a direct, yet matrix-effect tolerant, analytical method for determining DAAs in the plasma of ESRD patients while maintaining a moderate cost per sample and with an improved analyte extraction recovery. METHODS: In this study, a liquid chromatography-tandem mass spectrometric (LC-MS/MS) method was developed for the analysis of ombitasvir (OMB), paritaprevir (PRT) and ritonavir (RIT) in plasma. Sample preparation was performed using the liquid-liquid extraction (LLE) method. Isocratic separation was performed using a mixture of methanol and 10 mM ammonium acetate (79:21, v/v) followed by MS/MS detection. The method was validated and applied to determine DAAs in the plasma of ESRD patients (n = 7). RESULTS: The developed method was linear (r2 > 0.995), accurate (89.4 ± 7.8 to 108.3 ± 3.0) and precise (% CV 0.9-15.0) and showed improved recovery (> 80) over previously published ones in the range 5-250, 30-1,500, 20-1,000 ng/mL for OMB, PRT and RIT, respectively. Relative matrix effect was absent, and the method accurately determined the three DAAs in real-life samples (n = 7). CONCLUSIONS: An efficient analytical method for the determination of DAAs is presented. The method overcomes the potential analytical response fluctuation in ESRD. The developed method show improved extraction recoveries and is suitable for routine application in developing economies where hepatitis C virus is most prevalent.

Primary ovarian carcinoid: A report of two cases and a decade registry.

OBJECTIVES: This study aims at reporting 2 cases of primary ovarian carcinoid tumor, and providing an adequate registry of such cases and how they were managed. METHODS: 2 female patients with primary ovarian carcinoid were diagnosed and treated in our center. Discussion of their presentation, pathology and treatment is entitled. Also a thorough search of all published registries and case reports of ovarian carcinoid was done with analysis of reported data. RESULTS: 164 cases of primary ovarian carcinoid tumor were detected since 2005 with the predominance of the insular variant. Carcinoid syndrome occurs in nearly 14% of these cases. Most of the cases were treated with hysterectomy. Unfortunately, the prognosis was not documented in most series. CONCLUSION: Primary ovarian carcinoid is a relatively rare disease with an indolent course and excellent outcome. Carcinoid syndrome, especially carcinoid heart disease may worsen the prognosis. Total abdominal hysterectomy with bilateral salpingo-oophorectomy has been commonly used as the treatment of choice of primary ovarian carcinoid tumors.