Experimental study of tacrolimus immunosuppression on the mode of administration: efficacy of constant intravenous infusion avoiding Cmax

Ishibashi, M; Yoshida, Katsunori; Ozono, Seiichiro; Hirao, Yoshihiko; Takahashi, K; Kawamura, Yuji; Ohara, Kousuke

doi:10.1016/s0041-1345(00)02142-4

Cited by 13 publications

(8 citation statements)

References 9 publications

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“…29 Conversion from twice- to once-daily tacrolimus resulted in reduced hyperglycemia and triglycerides. 30-32 Bias, which cannot be repressed in this pilot study, are older age of patients, alcoholic cirrhosis in medical history and time after transplantation. These parameters might have negatively influenced the 4-TTMT results.…”

Section: Discussionmentioning

confidence: 65%

Cognitive Evaluation in Liver Transplant Patients Under Calcineurin Inhibitor Maintenance Therapy

Heits

Keserovic

Mund

et al. 2017

Transplantation Direct

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BackgroundNeurological disorders due to calcineurin inhibitor (CNI) treatment pose a well-known problem after liver transplantation (LTx). In this study, the impact of CNIs on cognitive functioning during maintenance therapy was analyzed. A possible improvement of cognitive functioning, compliance and health-related quality of life (HRQoL) after conversion to a once-daily tacrolimus formulation was prospectively assessed.MethodsIn a cross-section analysis cognitive functioning of living donors (LD), waiting list patients and LTx patients was tested using a 4 times trail making test (4-TTMT). In a further investigator-initiated trial a possible improvement of cognitive functioning, HRQoL and compliance after conversion to the once-daily tacrolimus formulation was prospectively assessed over 1 year. HRQoL was assessed using an EORTC-QLQ C30 questionnaire and patient’s compliance was assessed by the Basel Assessment of Compliance with Immunosuppressive Medication Scales questionnaire. Correlated data were sex, age, time after surgery, liver disease, model of end-stage liver disease score, creatinine, CNI type, and CNI trough levels.ResultsTwo hundred eleven patients were included in this cross-section analysis. Twenty-seven patients agreed to participate in the investigator-initiated trial. LTx patients completed the 4-TTMT slower than living donor patients and faster than waiting list patients. Patients with twice daily cyclosporine A (CSA) formulation needed longer to finish the 4-TTMT than patients with the once-daily tacrolimus formulation. After drug conversion of a twice-daily CNI formulation to a once-daily tacrolimus formulation, CSA-treated patients needed longer to improve their cognitive functioning. HRQoL and compliance did not improve after drug conversion.ConclusionsPatients with once-daily tacrolimus formulation had a better psychomotor speed than CSA-treated patients. The conversion to once-daily tacrolimus formulation significantly improved cognitive functioning, but had no impact on HRQoL or compliance.

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Section: Discussionmentioning

confidence: 65%

Cognitive Evaluation in Liver Transplant Patients Under Calcineurin Inhibitor Maintenance Therapy

Heits

Keserovic

Mund

et al. 2017

Transplantation Direct

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“…We have hypothesized that the C max may be closely related to its toxicity, and the use of once-daily tacrolimus would be less toxicity by the lower C max (12). In an experimental animal model, avoidance of high peak concentrations has been associated with a reduced incidence of hyperglycemia (19). Mecule et al (20) reported significant reductions in the incidence of hyperglycemia after conversion from Tacrolimus BID to Tacrolimus QD.…”

Section: Discussionmentioning

confidence: 99%

Comparison of Pharmacokinetics and Pathology for Low-Dose Tacrolimus Once-Daily and Twice-Daily in Living Kidney Transplantation

et al. 2013

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“…25,26 Although an elevated C max has been associated with the worsening of glucose control and triglyceride levels, it is possible that despite achieving targeted tacrolimus trough concentrations and similar overall AUC values, increased exposure in the early period after dose administration may contribute to toxicities (e.g., tremor, headache) in some patients. 27,28 Unfortunately, given our inclusion criteria of enrolling only clinically stable patients and the use of a single time point after transplantation, our study did not capture clinical outcomes to test this hypothesis. Further pharmacokinetic studies comparing clinical measurements and individualization of therapy in patients receiving corticosteroid-free regimens may be warranted.…”

Section: Mean ± Sdmentioning

confidence: 99%

Pharmacokinetics of tacrolimus and mycophenolate mofetil in renal transplant recipients on a corticosteroid-free regimen

Greanya

Poulin²,

Partovi

et al. 2012

American Journal of Health-System Pharmacy

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Overall exposure and C(min) values for tacrolimus were similar but C(max) values were higher than those documented in renal transplant patients treated with corticosteroid-based regimens. This may have clinical implications in corticosteroid-free patients experiencing symptoms of tacrolimus toxicity despite trough levels within target ranges. Mycophenolic acid exposure increased with time, but AUC values fell within the range expected for patients receiving concurrent corticosteroids.

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Experimental study of tacrolimus immunosuppression on the mode of administration: efficacy of constant intravenous infusion avoiding Cmax

Cited by 13 publications

References 9 publications

Cognitive Evaluation in Liver Transplant Patients Under Calcineurin Inhibitor Maintenance Therapy

Cognitive Evaluation in Liver Transplant Patients Under Calcineurin Inhibitor Maintenance Therapy

Comparison of Pharmacokinetics and Pathology for Low-Dose Tacrolimus Once-Daily and Twice-Daily in Living Kidney Transplantation

Pharmacokinetics of tacrolimus and mycophenolate mofetil in renal transplant recipients on a corticosteroid-free regimen

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