Pharmacokinetics and target attainment of mycophenolate in pediatric renal transplant patients

Martial, Lisa C.; Jacobs, Bart; Cornelissen, Elisabeth A.M.; Haan, A.F.J. de; Koch, Birgit C. P.; Burger, David M.; Aarnoutse, Rob E.; Schreuder, Michiel F.; Brüggemann, Roger J. M.

doi:10.1111/petr.12695

Cited by 15 publications

(20 citation statements)

References 43 publications

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“…One recent study suggests that dosing MMF to achieve a target MPA AUC 12 >35 mg.h/L is likely to lead to better efficacy and outcomes in patients with autoimmune diseases . Other studies set therapeutic targets at AUC 0‐12 h of 30–60 mg.h/L or trough levels ranging between 1.0 and 5.0 μg/mL depending on the condition being treated . The dose used in this study resulted in a comparable exposure to MPA (mean AUC 0‐14 h 32 mg.h/L).…”

Section: Discussionmentioning

confidence: 83%

Pharmacokinetics of Mycophenolic Acid after Intravenous Administration of Mycophenolate Mofetil to Healthy Cats

Slovak

Rivera

Hwang

et al. 2017

Veterinary Internal Medicne

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BackgroundMycophenolate mofetil (MMF), the prodrug of mycophenolic acid (MPA), is becoming increasingly popular as an alternative immunosuppressant in feline medicine. Pharmacokinetic information is not available for cats.ObjectiveThe purpose of this study was to determine whether MMF is biotransformed into the active metabolite MPA and to evaluate the disposition of MPA after a 2‐hour constant rate intravenous (IV) infusion of MMF in healthy cats.AnimalsHealthy cats (n = 6).MethodsThis was a prospective pilot study. All cats were administered MMF at 20 mg/kg every 12 hours over a 2‐hour constant rate infusion for 1 day. The concentrations of MPA and its derivatives in blood were determined using a validated UHPLC–UV method.ResultsAll cats biotransformed MMF into MPA. The mean AUC0‐14 h ranged from 6 to 50 h*mg/L after IV dosing of MMF. Transient large bowel diarrhea was recorded in 2 of 6 cats after medication administration.Conclusion and Clinical ImportanceThe disposition of MPA in plasma was highly variable, which could result in high interindividual variability in the safety and efficacy of treatment with MMF in cats.

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Section: Discussionmentioning

confidence: 83%

Pharmacokinetics of Mycophenolic Acid after Intravenous Administration of Mycophenolate Mofetil to Healthy Cats

Slovak

Rivera

Hwang

et al. 2017

Veterinary Internal Medicne

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“…In cats and dogs, the disposition of MPA seems to be highly variable (Ackermann et al., ; Slovak, Rivera, et al., ), as reported in humans (Le Meur et al., ; Zabotti et al., ; Mok, ). Variability in drug disposition of MPA could result in unpredictable safety and efficacy and explain interindividual variability in drug tolerance (Streicher et al., ; Martial et al., ; Filler, Alvarez‐Elías, McIntyre, & Medeiros, ; Zhang & Chow, ).…”

Section: Introductionmentioning

confidence: 99%

Ex vivo binding of the immunosuppressant mycophenolic acid to dog and cat plasma proteins and the effect of co‐incubated dexamethasone and prednisolone

Morassi

Vélez

Slovak

et al. 2018

Vet Pharm & Therapeutics

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Mycophenolic acid (MPA) has been shown to be promising for the treatment of autoimmune diseases in dogs and cats. In humans, MPA is highly bound to plasma proteins (~97%). It has been recommended to monitor free drug plasma concentrations because the free MPA correlates with its immunosuppressive effect. However, it is unknown if MPA is highly bound to plasma proteins in dogs and cats. The objectives of this study were to determine the extent of plasma protein binding of MPA and evaluate the effect of prednisolone and dexamethasone on the extent of protein binding of MPA in dogs and cats. The extent of plasma protein binding of MPA was determined in plasma collected from clinically healthy adult cats (n = 13) and dogs (n = 14) by combining high-throughput dialysis and ultra-high-liquid chromatography. This study reveals that MPA is highly bound to plasma proteins (>90%) in dogs and cats, mean extent of binding of MPA at 15 μg/ml to plasma proteins being 96% (range, 95%-97%) and 92% (range, 90%-93%) for dogs and cats, respectively. In dog plasma, MPA is primarily bound to albumin. In vitro, prednisolone increased the unbound MPA in dogs (p < .01) but not in cats (p = .07) while dexamethasone had no effect on MPA plasma binding in either species (p > .05). Results of this study provide valuable information for designing future pharmacokinetic and pharmacodynamic studies and also therapeutic monitoring programs for dogs and cats.

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“…methotrexate) and immunosuppressants (e.g. cyclosporine, tacrolimus) [1–3]. The purpose of concentration guided dose adaptation is to maintain drug exposure within predefined targets to ensure adequate efficacy and to decrease the likelihood of adverse events [4].…”

Section: Introductionmentioning

confidence: 99%

“…The purpose of concentration guided dose adaptation is to maintain drug exposure within predefined targets to ensure adequate efficacy and to decrease the likelihood of adverse events [4]. Conventionally, drug concentrations are measured in plasma, serum or whole blood obtained by venous sampling in a specialized healthcare facility [2, 3]. For patients treated on an outpatient basis, regular blood sampling can be challenging.…”

Section: Introductionmentioning

confidence: 99%

Cost Evaluation of Dried Blood Spot Home Sampling as Compared to Conventional Sampling for Therapeutic Drug Monitoring in Children

et al. 2016

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Dried blood spot (DBS) sampling for the purpose of therapeutic drug monitoring can be an attractive alternative for conventional blood sampling, especially in children. This study aimed to compare all costs involved in conventional sampling versus DBS home sampling in two pediatric populations: renal transplant patients and hemato-oncology patients. Total costs were computed from a societal perspective by adding up healthcare cost, patient related costs and costs related to loss of productivity of the caregiver. Switching to DBS home sampling was associated with a cost reduction of 43% for hemato-oncology patients (€277 to €158) and 61% for nephrology patients (€259 to €102) from a societal perspective (total costs) per blood draw. From a healthcare perspective, costs reduced with 7% for hemato-oncology patients and with 21% for nephrology patients. Total savings depend on the number of hospital visits that can be avoided by using home sampling instead of conventional sampling.

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Pharmacokinetics and target attainment of mycophenolate in pediatric renal transplant patients

Cited by 15 publications

References 43 publications

Pharmacokinetics of Mycophenolic Acid after Intravenous Administration of Mycophenolate Mofetil to Healthy Cats

Pharmacokinetics of Mycophenolic Acid after Intravenous Administration of Mycophenolate Mofetil to Healthy Cats

Ex vivo binding of the immunosuppressant mycophenolic acid to dog and cat plasma proteins and the effect of co‐incubated dexamethasone and prednisolone

Cost Evaluation of Dried Blood Spot Home Sampling as Compared to Conventional Sampling for Therapeutic Drug Monitoring in Children

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