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ORIGINAL RESEARCH article
Front. Vet. Sci.
Sec. Veterinary Pharmacology and Toxicology
Volume 11 - 2024 |
doi: 10.3389/fvets.2024.1444586
Progression of cyclosporine A-blood levels in experimental cats receiving a high dosed treatment protocol
Provisionally accepted
Sarah Rösch
1*
Anna Frommeyer
1*
Jenny Schulte Bocholt
1*
Denis Grote-Koska
2
Korbinian Brand
2
Reinhard Mischke
1*- 1 Small Animal Clinic, University of Veterinary Medicine Hanover Foundation, Hannover, Germany
- 2 Institute of Clinical Chemistry, Hannover Medical School, Hannover, Germany
Background: Cyclosporine A (CsA) is used as a steroid sparing or alternative immunosuppressing agent in cats with various immune-mediated diseases such as immune-mediated hemolytic anemia. Daily treatment dosages of 5–20 mg/kg have been described. Interindividual variations in CsA blood levels are known to occur. To determine when steady state conditions are reached and thus the earliest advisable time for monitoring CsA blood levels during the course of treatment, a prospective experimental study was conducted in six healthy adult domestic short hair cats. Materials and Methods: Cats were treated with an oral dosage of 7 mg/kg CsA q 12 hours for 10 days. On days 1, 2, 3, 5, 7, and 10 after the start of CsA administration (i.e. after 1, 3, 5, 9, 13, and 19 CsA administrations), EDTA blood was collected to measure the CsA level 12 hours after the CsA administration (trough values) using high-performance liquid chromatography coupled to mass spectrometry (HPLC-MS/MS). Results: Statistical analysis revealed a significant increase in mean CsA blood levels up to day 5 (2050 ± 964.2 ng/ml [mean ± SD], 832–3203 ng/ml [minimum–maximum]; repeated measures ANOVA: P = 0.0021), while values on days 5 and 7 did not differ significantly from CsA concentrations on day 10. CsA concentrations showed marked interindividual variability. Conclusions: CsA blood levels reached steady state on day 5 of high dosages of CsA q 12 hours (i.e. after 9 CsA administrations), indicating that this early time point is suitable for monitoring blood levels in clinical patients. Results confirmed the well-known remarkable interindividual variability of CsA, indicating the need for treatment monitoring. The assessed treatment regime resulted in significantly higher mean CsA trough levels than the target range for immunosuppressive therapy (200–600 ng/ml).
Keywords: Ciclosporin, Drug Monitoring, LC-MS/MS, Calcineurin inhibitor, systemic 24 immunosuppressant, Oral, drug, therapeutic blood level
Received: 05 Jun 2024; Accepted: 13 Sep 2024.
Copyright: © 2024 Rösch, Frommeyer, Schulte Bocholt, Grote-Koska, Brand and Mischke. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Sarah Rösch, Small Animal Clinic, University of Veterinary Medicine Hanover Foundation, Hannover, 30559, Germany
Anna Frommeyer, Small Animal Clinic, University of Veterinary Medicine Hanover Foundation, Hannover, 30559, Germany
Jenny Schulte Bocholt, Small Animal Clinic, University of Veterinary Medicine Hanover Foundation, Hannover, 30559, Germany
Reinhard Mischke, Small Animal Clinic, University of Veterinary Medicine Hanover Foundation, Hannover, 30559, Germany
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