Description:

The present study aimed to explore the effects of cimetidine on ciclosporin population pharmacokinetics and initial dose optimization in aplastic anemia patients. Aplastic anemia patients were used to establish a population pharmacokinetic model by the nonlinear mixed effect, and concentrations of ciclosporin were simulated by Monte Carlo method. With the same weight, the ciclosporin clearance rates were 0.387:1 in patients with or without cimetidine, respectively. In the measured ciclosporin concentrations, compared to aplastic anemia patients without cimetidine, ciclosporin concentrations were higher in patients with cimetidine (P < 0.01). Further research found that at the same body weight and same dose, ciclosporin concentrations in aplastic anemia patients with cimetidine were indeed higher than those in patients without cimetidine (P < 0.01). The initial recommended ciclosporin dose for patients without cimetidine was 7mg/kg splited into two doses for weight of 40-60kg, and 6mg/kg splited into two doses for weight of 60-100kg. The patients with cimetidine were recommended to take 3mg/kg ciclosporin splited into two doses for weight of 40-100kg. It was the first time to explore the effects of cimetidine on ciclosporin population pharmacokinetics and initial dose optimization in aplastic anemia patients. Patient’s coadministration of cimetidine may need low ciclosporin dose.

Several HLA allele associations with aplastic anemia have been reported around the world. However, due to a lack of such association studies in the Indian population, the current study looked at the frequency of HLA class I (A, B, and C loci) and II (DRB1 and DQB1 loci) with aplastic anemia to see if there was an association between the HLA allele and the disease. A total of 49 aplastic anemia patients (cases) and 100 healthy participants (controls) were included in the study. All of these samples were HLA typed for HLA-A,-B -C,-DRB1, and DQB1 loci using a polymerase chain reaction sequence-specific oligonucleotide probe approach. A positive association of HLA-DRB1*15:02 (p =0.00001269, OR=4.275), was found with AA. Whereas HLA-C*07:01 (p = 0.0017318, OR = 0.179) and HLA-DQB1*02:01 (p =0.00017033, OR = 0.371) were found to be negatively associated. Our findings are the first to show an association between class I and II HLA alleles and aplastic anemia in the Indian population, and they can be used to further investigate aplastic anemia studies.

A 65-year-old man with no severe aplastic anemia received rabbit anti-thymocyte globulin and cyclosporine and partially responded. Six months after the initiation of treatment, he was diagnosed with stage IV angioimmunoblastic T-cell lymphoma and received chemotherapy. PET/CT scan analysis indicated a complete response. However, he showed sustained myelosuppression and was diagnosed with relapse of aplastic anemia. He did not respond to cyclosporine, eltrombopag or methenolone. Fifteen months after eltrombopag administration, he developed MDS with t (3; 21) (q26.2; q22). Patients should be monitored carefully for the emergence of not only-7/del (7q) but also 3q26 abnormalities, including t (3; 21) (q26.2; q22), during and after eltrombopag treatment.

Severe Aplastic Anemia (SAA) is a life-threatening bone marrow failure disease. Allogeneic hematopoietic stem cell transplantation from a Matched Sibling Donor (MSD-HSCT) and intensive immunosuppressive therapy (IST) are 2 major comparable treatments for SAA. As the addition of eltrombopag (EPAG) to standard IST therapy has greatly improved the survival prognosis of SAA, whether MSD-HSCT or IST/EPAG is the better choice has become a matter of debate. A study was performed involving 99 patients with newly diagnosed acquired SAA from 5 medical centers, including 48 MSD-HSCT cases and 51 IST/EPAG cases, which consisted of rabbit antithymocyte globulin or porcine-antilymphocyte globulin, cyclosporine plus eltrombopag.

With Regards

sarfania
Journal Coordinator
Global Journal of Research and Review