The progression of the nonalcoholic fatty liver disease to nonalcoholic steatohepatitis (NASH) is multifactorial, and there is still a lack of approved medications for its treatment. The study aimed to evaluate the impact of combined treatment with Pentoxifylline and Metformin on biochemical parameters in patients with NASH. Setting: Outpatient hepatology clinic.
A prospective trial was conducted. The first cohort included patients with biopsy-proven NASH, while the second cohort consisted of patients with biopsy-confirmed NAFLD. Blood tests were checked at baseline and every three months. Pentoxifylline at a dosage of 400 mg t.i.d. and Metformin at the dosage of 500 mg t.i.d. were introduced for six months in NASH group. The impact of the treatment was assessed based on biochemical results after combined treatment with low-cost medications.
All 33 NASH patients completed 24 weeks of treatment. We observed significant improvement (p<0.05) of median values after treatment for the following parameters: serum uric acid levels decreased by 51.0 micromol/L, calcium decreased for 0.27 mmoL/L, magnesium showed an increase of 0.11 mmoL/L. Insulin resistance improved as a reduction of HOMA – IR by 1.3 was detected. A significant decrease of median in liver enzymes, alanine aminotransferase, aspartate aminotransferase and gammaglutamyltransferase by 24.0 IU/L, 9.1 IU/L, 10.8 IU/L respectively, was noted.
Pentoxifylline and Metformin may provide possible treatment option in NASH. Some new potential benefit of the therapy in improving liver function whilst decreasing cardiovascular risk was perceived.
Bojana Golubović, Katarina Vučićević, Dragana Radivojević, Sandra Vezmar Kovačević, Milica Prostran and Branislava Miljković
Due to wide intra- and inter-individual pharmacokinetic variability and narrow therapeutic index of sirolimus, the therapeutic drug monitoring (TDM) of sirolimus with detailed biochemical and clinical monitoring is necessary for dose individualization in kidney transplant patients. The purpose of the study was to explore and identify factors that contribute to pharmacokinetic variability by developing and validating a population model using routine TDM data and routinely monitored biochemical and clinical parameters.
The data obtained by routine monitoring of 38 patients over a period of one year from the sirolimus treatment initiation, were collected from patients’ records. Population analysis was performed using the software NONMEM®. The validity of the model was tested by the internal and external validation techniques.
The pharmacokinetic variability was partially explained with patient’s age and liver function. CL/F was found to decrease with age. According to the developed model, sirolimus CL/F decreases by, in average, 37% in patients with aspartate aminotransferase (AST) greater than 37 IU/L. The internal and external validation confirmed the satisfactory prediction of the developed model.
The population modeling of routinely monitored data allowed quantification of the age and liver function influence on sirolimus CL/F. According to the final model, patients with compromised liver function expressed via AST values require careful monitoring and dosing adjustments. Proven good predictive performance makes this model a useful tool in everyday clinical practice.