Efficacy and safety of tacrolimus versus mycophenolate mofetil as induction treatment and low-dose tacrolimus as treatment for lupus nephritis: a meta-analysis

Lee, Young Ho; Song, Gwan Gyu

doi:10.1007/s00393-022-01313-2

Cited by 1 publication

(1 citation statement)

References 32 publications

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“…Voclosporin achieved a complete renal response rate of 43% in lupus trials [ 3 ]. Even as an induction therapy, the multitargeted treatment of lupus nephritis with voclosporin and mycophenolate proved equivalent to tacrolimus and mycophenolate [ 16 ]. For the most dramatic form of acute kidney disease, that is, rapidly progressive glomerulonephritis, protocols containing voclosporin still must be investigated and compared to the established regimes [ 32 ].…”

Section: Conclusion and Practical Consequencesmentioning

confidence: 99%

Clinical Pharmacokinetics and Pharmacodynamics of Voclosporin

Abdel-Kahaar

Keller

2023

Clin Pharmacokinet

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Voclosporin is an approved option for the long-term treatment of lupus nephritis. We aimed to provide a narrative review of the pharmacokinetics and pharmacodynamics of voclosporin. In addition, we derived values for pharmacokinetic and pharmacodynamic parameters by graphical analysis of published diagrams. Compared with cyclosporin, low-dose voclosporin is associated with a lower nephrotoxicity risk and, compared to tacrolimus, with a lower diabetes risk. After repetitive dosing of 23.7 mg twice daily and at target trough concentrations of 10–20 ng/mL, the dominant or effect-indicative half-life is estimated at 7 hours. Compared with the pharmacodynamics of cyclosporin, the potency of voclosporin is stronger, with a lower concentration CE 50 of 50 ng/mL already producing the half-maximum immunosuppressive effect. The Hill coefficient can be predicted to be low at H = 1.3, indicating a concentration-dependent effect on the immune system. The corresponding effect bisection time of 10 hours allows for dosing every 12 hours. Accordingly, the trough concentration will be above the threshold concentration that produces 5% of the maximum effect of 5.2 ng/mL for immunosuppression but below both the predicted threshold of 30 ng/mL for nephrotoxicity and the predicted threshold of 40 ng/mL for new-onset diabetes. The pharmacokinetic and pharmacodynamic properties suggest the use of low-dose voclosporin combined with mycophenolate and low-dose glucocorticoids for immunosuppressive maintenance therapy.

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Section: Conclusion and Practical Consequencesmentioning

confidence: 99%