Pharmacokinetics of mycophenolate mofetil following single-dose intravenous and single- and multiple-dose oral administration and clinicopathologic effects of mycophenolate mofetil following long-term oral administration in healthy horses.
Abstract: To characterize the pharmacokinetics of mycophenolate mofetil (MMF) following single-dose IV or PO administration, characterize the pharmacokinetics of MMF following long-term PO administration, and describe the clinicopathologic effects of long-term MMF administration in horses. Methods: 12 healthy adult horses. Methods: In phase 1, 6 horses received a single IV (2.5 mg/kg) or PO (5 mg/kg) dose of MMF in a randomized balanced crossover assessment (≥ 2-week interval between administrations). In phase 2, 6 other horses received MMF for 60 days (5 mg/kg, PO, q 24 h for 30 days and then 5 mg/kg, PO, q 48 h for an additional 30 days). Results: Following IV (single-dose) or PO (single- or multiple-dose) administration, MMF was rapidly converted to mycophenolic acid. For single-dose PO administration, mean ± SD maximum plasma mycophenolic acid concentration was 1,778.3 ± 441.5 ng/mL at 0.71 ± 0.29 hours. For single-dose IV administration, mean systemic clearance and volume of distribution at steady state were 0.689 ± 0.194 L/h/kg and 1.57 ± 0.626 L/kg, respectively. Following single doses, mean terminal half-life was 3.99 ± 0.865 hours for IV administration and 4.02 ± 1.01 hours for PO administration. The accumulation index following long-term PO administration was 1.0 ± 0.002, and the terminal half-life was 4.59 ± 1.25 hours following the final dose on day 60. None of the horses developed abnormal clinical signs or had any consistently abnormal clinicopathologic findings. Conclusions: Further investigation of the clinical efficacy of long-term MMF treatment of horses with autoimmune diseases is warranted.
Publication Date: 2021-05-26 PubMed ID: 34032479DOI: 10.2460/ajvr.82.6.502Google Scholar: Lookup
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- Journal Article
Summary
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The study investigates how a drug, mycophenolate mofetil (MMF), behaves in the body of healthy horses when administered intravenously or orally in single doses, as well as the effects of long-term oral doses. It found that MMF quickly converts to mycophenolic acid and no consistent abnormal clinical signs or findings were discovered in the horses.
Study Design and Methodology
- The research was carried out in two main phases and utilized 12 healthy adult horses in total.
- In the first phase, 6 of the horses were given a single dose of MMF either intravenously (IV) or orally (PO). The dosage for IV administration was 2.5 mg/kg and for PO administration, it was 5 mg/kg. The administration of MMF for this phase was done in a randomized balanced crossover design, with a pause of at least 2 weeks between each administration.
- In the second phase, the remaining 6 horses were given MMF orally over a continuous period of 60 days, starting with a dosage of 5 mg/kg every 24 hours for the first 30 days, followed by the same dosage every 48 hours for the following 30 days.
Pharmacokinetics of Mycophenolate Mofetil
- The study observed that MMF was rapidly converted to mycophenolic acid following either IV or oral administration.
- For a single dose administered orally, the concentration of mycophenolic acid in plasma was 1,778.3 ± 441.5 ng/mL at 0.71 ± 0.29 hours on average.
- In the case of single-dose IV administration, the average systemic clearance was 0.689 ± 0.194 L/h/kg and the volume of distribution at a steady state was 1.57 ± 0.626 L/kg.
- For both administration methods, the terminal half-life was on average around 4 hours.
- When administered orally over a long period, the accumulation index was almost 1.0 ± 0.002, and the terminal half-life was around 4.59 ± 1.25 hours following the final dose on day 60.
Clinicopathologic Effects of Mycophenolate Mofetil
- None of the horses exhibited any abnormal clinical signs or had consistently abnormal findings, indicating that the drug was well-tolerated.
Conclusions and Recommendations
- The researchers recommended further investigation into the clinical efficiency of long-term MMF treatment in horses suffering from autoimmune diseases based on the findings of this study.
Cite This Article
APA
Knych HK, McKemie DS, Kanarr KL, White SD.
(2021).
Pharmacokinetics of mycophenolate mofetil following single-dose intravenous and single- and multiple-dose oral administration and clinicopathologic effects of mycophenolate mofetil following long-term oral administration in healthy horses.
Am J Vet Res, 82(6), 502-509.
https://doi.org/10.2460/ajvr.82.6.502 Publication
Researcher Affiliations
MeSH Terms
- Administration, Oral
- Animals
- Area Under Curve
- Biological Availability
- Horses
- Immunosuppressive Agents
- Mycophenolic Acid
Citations
This article has been cited 1 times.- Bello K, Lorch G, Kim K, Toribio RE, Yan L, Xie Z, Hill K, Phelps M. Pharmacokinetics and tolerability of multiple-day oral dosing of mycophenolate mofetil in healthy horses. J Vet Intern Med 2023 Sep-Oct;37(5):1907-1916.
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