Decreased cyclosporine exposure during the remission of nephrotic syndrome

Medeiros-Domingo, Mara; Pèrez‐Urizar, José; Mejía-Gaviria, Natalia; Ramírez-López, Eduardo; Castañeda‐Hernández, Gilberto; Muñoz, Ricardo

doi:10.1007/s00467-006-0300-6

Cited by 9 publications

(15 citation statements)

References 40 publications

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“…To achieve comparable exposures, children require higher relative CSA doses compared to adults. Such differences are mainly caused by shorter intestinal surface absorption and a higher metabolic rate for CSA in children (14,16),. Therefore, adult studies cannot be applied to children.…”

Section: Discussionmentioning

confidence: 99%

“…Some studies have suggested that edema, hypoproteinemia, and hypercholesterolemia are involved in CSA bioavailability and clearance (13,16). Hypercholesterolemia is particularly important in CSA-PK because the drug is highly lipophilic and binds to blood cells and plasma proteins; the relative distribution depends on the temperature, drug concentration, hematocrit, and plasma lipoproteins (23).…”

Section: Discussionmentioning

confidence: 99%

“…If this is so, then different TDM might be necessary during each of these periods. Furthermore, it is important to find a drug that is effective and safe (13,16). …”

Section: Introductionmentioning

confidence: 99%

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Pharmacokinetics of cyclosporin - a microemulsion in children with idiopathic nephrotic syndrome

Henriques¹,

Matos²,

Vaisbich³

2012

Clinics

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OBJECTIVE:We present a prospective study of a microemulsion of cyclosporin to treat idiopathic nephrotic syndrome in ten children with normal renal function who presented cyclosporin trough levels between 50 and 150 ng/ml and achieved complete remission with cyclosporin. To compare the pharmacokinetic parameters of cyclosporin in idiopathic nephrotic syndrome during remission and relapse of the nephrotic state.METHOD:The pharmacokinetic profile of cyclosporin was evaluated with the 12-hour area under the time-concentration curve (auc0-12) using seven time-point samples. This procedure was performed on each patient during remission and relapse with the same cyclosporin dose in mg/kg/day. The 12-hour area under the time-concentration curve was calculated using the trapezoidal rule. All of the pharmacokinetic parameters and the resumed 4-hour area under the time-concentration curve were correlated with the 12-hour area under the time-concentration curve. ClinicalTrials.gov: NCT01616446.RESULTS:There were no significant differences in any parameters of the pharmacokinetic of cyclosporin during remission and relapse, even when the data were normalized by dose. The best correlation with the 12-hour area under the time-concentration curve was the 4-hour area under the time-concentration curve on remission and relapse of the disease, followed by the 2-hour level after cyclosporin (c2) dosing in both disease states.CONCLUSIONS:These data indicate that the same parameters used for cyclosporin therapeutic monitoring estimated during the nephrotic state can also be used during remission. Larger controlled studies are needed to confirm these findings.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Pharmacokinetics of cyclosporin - a microemulsion in children with idiopathic nephrotic syndrome

Henriques¹,

Matos²,

Vaisbich³

2012

Clinics

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“…Nozu et al (2005) reported that 33% of pediatric nephrotic patients present a late peak absorption and discourage the use of C2 as monitoring tool in this population. Our group has recently reported a decrease in CsA exposure in pediatric patients during remission of nephrotic syndrome, suggesting that the target area under the curve (AUC) cannot be the same throughout the treatment (Medeiros et al 2007). At present, CsA dosing regimens are frequently designed according to pharmacokinetic information-derived transplant recipients.…”

Section: Introductionmentioning

confidence: 97%

Increased cyclosporine bioavailability induced by experimental nephrotic syndrome in rats

Medeiros-Domingo

Pèrez‐Urizar

Pedraza‐Chaverrí

et al. 2007

Can. J. Physiol. Pharmacol.

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Components of whole blood and plasma are highly altered during the presentation of nephrotic syndrome. The present study was aimed to explore the influence of nephrotic syndrome on the pharmacokinetics of cyclosporine (CsA) (10 mg/kg) administered i.v. to control or puromycin-induced nephrotic rats (P-NS). We found an increase in CsA bioavailability in the nephrotic group compared with controls. The area under the curve of blood CsA versus time (AUCiv) increased from 27.7 +/- 5.3 to 60.6 +/- 13.8 mug.h.mL-1 in control and P-NS rats, respectively. The AUCiv augmentation was positively correlated with cholesterol levels. On the other hand, the total body clearance was significantly lower (0.38 +/- 0.06 vs. 0.17 +/- 0.03 L.(kg body mass)-1.h-1) and the volume of distribution at steady state (3.70 +/- 0.52 vs. 2.85 +/- 0.32 L/kg) was significantly smaller in nephrotic rats as compared with control. These pharmacokinetic changes lead to a longer terminal half-life of CsA in P-NS rats (11.8 +/- 1.6 vs. 6.9 +/- 0.91 h). We conclude that the physiopathologic changes induced by the nephrotic syndrome in P-NS animals result in a significant increase in CsA blood exposure by both the decrease in drug distribution and the reduction in elimination rate of CsA.

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“…The incidence of CsAN increases the younger the patient is at start of therapy and the longer the duration is [48]. Performing therapeutic drug monitoring in children with FRNS one has to consider that CsA exposure is lower in remission than during relapse [49] due to hyperlipidemia and consecutive lipid binding of CsA. The functional relevance of this finding toward efficacy and toxicity, however, is unclear.…”

Section: Cyclosporinementioning

confidence: 95%

Treatment of children with frequently relapsing steroid-sensitive nephrotic syndrome: recent trial results

Benz¹,

Toenshoff²,

Weber³

2014

Clinical Investigation

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Despite being an orphan disease idiopathic nephrotic syndrome in children is the most frequent glomerular disease in this age group. A total of 80-90% of children between 2 and 10 years of age respond to corticosteroids, but carry the risk of relapses that may even appear frequently (frequently relapsing nephrotic syndrome, [FRNS]). To avoid repeated courses of corticosteroids and associated drug toxicity in these patients manifold strategies for a corticosteroid-sparing treatment of FRNS exist, but evidence on their efficacy and safety is low. This article discusses the results of recent therapeutic trials on FRNS and their possible impact on existing guidelines. Since the prognosis of steroid-sensitive nephrotic syndrome toward renal function is generally good, not only the efficacy but also the toxicity of different treatment regimens is discussed.

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Decreased cyclosporine exposure during the remission of nephrotic syndrome

Cited by 9 publications

References 40 publications

Pharmacokinetics of cyclosporin - a microemulsion in children with idiopathic nephrotic syndrome

Pharmacokinetics of cyclosporin - a microemulsion in children with idiopathic nephrotic syndrome

Increased cyclosporine bioavailability induced by experimental nephrotic syndrome in rats

Treatment of children with frequently relapsing steroid-sensitive nephrotic syndrome: recent trial results

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