Pharmacodynamic Monitoring of Cyclosporin

Awni, Walid M.

doi:10.2165/00003088-199223060-00004

Cited by 32 publications

(12 citation statements)

References 88 publications

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“…The relevance of AUC, maximal concentration (C max ) and trough concentration (C trough ) values for predicting the efficacies and safety is not fully known for all clinically approved immunosuppressants. Therefore, determination of the relationships between PD and PK may improve utility of PK monitoring (14).…”

Section: Barten Et Almentioning

confidence: 99%

Pharmacodynamics of Mycophenolate Mofetil after Heart Transplantation: New Mechanisms of Action and Correlations with Histologic Severity of Graft Rejection

Barten

Gelder

Gummert

et al. 2002

American Journal of Transplantation

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The primary mechanism of action in vivo of mycophenolate mofetil (MMF) is believed to be inhibition of lymphocyte proliferation. We used novel assays of lymphocyte functions (pharmacodynamics, PD) in whole blood collected from rat heart allograft recipients treated with MMF to investigate the mechanisms of action of the active metabolite of MMF, mycophenolate acid (MPA) in vivo. Allograft recipients were treated orally once daily with 3 different doses of MMF. Seven days after transplantation, blood was collected 24 h after the penultimate dose and several timepoints after the last dose, after which grafts were removed for microscopic grading of rejection. Lymphocytes in whole blood samples were mitogen stimulated through calcium-dependent and -independent signaling pathways. Inhibition of PD was measured by lymphocyte proliferation and expression of several surface antigens on T cells, and was calculated as area under the time-inhibition of immune function effect curve (AUE 0ª24 h ). We found that inhibition of lymphocyte proliferation and antigen expression by MPA correlated highly with MMF-dose, MPA level and with the histologic severities of graft rejection (p ∞0.05). In summary, MPA suppressed lymphocyte proliferation and expression of T-cell surface antigens in whole blood collected from MMF-treated allograft recipients, thus demonstrating the multiple mechanisms of suppression of rejection on peripheral blood T cells after MMF treatment.

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Section: Barten Et Almentioning

confidence: 99%

Pharmacodynamics of Mycophenolate Mofetil after Heart Transplantation: New Mechanisms of Action and Correlations with Histologic Severity of Graft Rejection

Barten

Gelder

Gummert

et al. 2002

American Journal of Transplantation

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“…Cyclosporine is a calcineurin inhibitor that was developed for the treatment of many immune-mediated diseases, in particular, for the prevention of allograft rejection after solid organ transplantation [11,12] . Leukocytes and special helper CD4 + lymphocytes are the main therapeutic targets of this drug [13,14] .…”

Section: Introductionmentioning

confidence: 99%

Effect of bifendate on the pharmacokinetics of cyclosporine in relation to the CYP3A4*18B genotype in healthy subjects

Zeng

et al. 2009

Acta Pharmacol Sin

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Aim:To evaluate the potential drug-drug interactions between bifendate and cyclosporine, a substrate of CYP3A4, in relation to different CYP3A4*18B genotype groups. Methods: Eighteen unrelated healthy subjects (six CYP3A4*1*1, six CYP3A4*1/*18B, and six CYP3A4*18/*18B) were selected for this study. After repeated oral administration of a placebo or bifendate (three times daily for 14 d), the wholeblood level of cyclosporine was measured using high performance liquid chromatography-electrospray mass spectrometry (HPLC/ESI-MS). This study was carried out in a two-phase randomized crossover manner. Results: After the treatment with bifendate, the areas under the curve (AUC 0-24 and AUC 0-∞ ) decreased significantly by 9.7%±3.7% (P=0.01) and 19.2%±16.8% (P=0.001) in CYP3A4*1/*1 subjects, 11.3%±9.4% (P=0.03) and 10.5%±9.6% (P=0.043) in CYP3A4*1/*18B subjects, and 40.2%±14.7% (P=0.02) and 37.5%±15.8% (P=0.003) in CYP3A4*18B/*18B subjects. Meanwhile, the decreases in the AUC 0-24 and AUC 0-∞ values in the three groups were significantly different (using one-way analysis of variance, P=0.001 and P=0.001), and the change in the CYP3A4*18B/*18B group was greater than that in the other two groups. The oral clearance of cyclosporine was altered in all the subjects, with substantial increases by 10.2%±4.4% (P=0.004) in CYP3A4*1/*1 subjects, 14.0%±12.0% (P=0.048) in CYP3A4*1/*18B subjects, and 32.4%±21.7% (P=0.013) in CYP3A4*18B/*18B subjects. Conclusion: These results suggest that bifendate decreases the plasma concentration of cyclosporine in a CYP3A4 genotypedependent manner.

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“…They all had heavy proteinuria and suffered from growth retardation due to level or area under the curve (AUC) of CsA [3]. Unfortunately, the absorption of oral CsA varies widely, adverse effects of corticosteroids.…”

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confidence: 99%

Cyclosporin pharmacokinetics following administration of capsules and Neoral in paediatric patients with lupus nephritis

Yang

Chen

et al. 1997

Brit J Clinical Pharma

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Aims Neoral is a new microemulsion form of cyclosporin. Pharmacokinetic reports in children are scarce. Therefore, we performed a pharmacokinetic study between Cyclosporin A (CsA) capsules and Neoral in paediatric patients with lupus nephritis. Methods A single 5 mg kg−1 dose orally of either CsA capsules or Neoral was given to 10 paediatric patients (serum creatinine<1.5 mg dl−1 ). CsA whole blood levels were measured for 24 h post‐dose by h.p.l.c. Results Neoral had a higher Cmax and AUC(Cmax: 943±176 ng ml−1; AUC: 4612±785 ng ml−1 h) than those of the CsA capsules (Cmax: 697±187 ng ml−1; AUC: 3483±873 ng ml−1 h; P<0.05). There was no difference in tmax and t1/2,z between the two groups. Conclusions CsA Neoral had improved absorption and bioavailability, which is similar to what is reported in adults. However, interpatient variability still existed. Careful drug monitoring and dose adjustment should be performed during treatment to avoid nephrotoxicity, especially in lupus nephritis.

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Pharmacodynamic Monitoring of Cyclosporin

Cited by 32 publications

References 88 publications

Pharmacodynamics of Mycophenolate Mofetil after Heart Transplantation: New Mechanisms of Action and Correlations with Histologic Severity of Graft Rejection

Pharmacodynamics of Mycophenolate Mofetil after Heart Transplantation: New Mechanisms of Action and Correlations with Histologic Severity of Graft Rejection

Effect of bifendate on the pharmacokinetics of cyclosporine in relation to the CYP3A4*18B genotype in healthy subjects

Cyclosporin pharmacokinetics following administration of capsules and Neoral in paediatric patients with lupus nephritis

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