Cyclosporin pharmacokinetics following administration of capsules and Neoral in paediatric patients with lupus nephritis

Fu, Li-Wen; Yang, Lizhi; Chen, W. P.; Lin, Chinsu

doi:10.1046/j.1365-2125.1997.00634.x

Cited by 11 publications

(7 citation statements)

References 3 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The pharmacokinetic profile seems to be more stable in individual patients and the interpatient variability is decreased with Neoral as compared to Sandimmun. The results obtained in the present study in stable pediatric patients with steroid-dependent nephrotic syndrome are comparable to those obtained in stable pediatric patients with renal or liver transplants, as well as in patients with systemic lupus erythematosus [1][2][3][4]. In these studies, the use of Neoral results in an earlier peak concentration, with a higher Cmax and a higher AUC, while the trough levels are similar with both formulations.…”

Section: Methodssupporting

confidence: 84%

A pharmacokinetic study of Neoral in childhood steroid-dependent nephrotic syndrome

Niaudet¹,

Reigneau

Humbert

2001

Pediatric Nephrology

View full text Add to dashboard Cite

Seven children with steroid-dependent nephrotic syndrome who were on stable remission under Sandimmun therapy were switched to Neoral at the same dosage. During the 4-month follow-up period, two patients relapsed, due to poor compliance in one of them. Serum creatinine remained stable in all patients. Pharmacokinetic profiles were performed at day 0 while on Sandimmun and 4 weeks after conversion to Neoral. Following conversion to Neoral, the peak concentration occurred earlier (2+/-1.4 h vs 3.9+/-2.4 h), and the maximum concentration (677+/-386 ng/ml vs 488+/-265 ng/ml) and the area under the curve (3,082+/-1,536 ng/ml/h vs 2,201+/889 ng/ml/h) were higher. We conclude that Neoral results in an increased bioavailability of cyclosporine (CsA) as compared to Sandimmun in patients with steroid-dependent nephrotic syndrome in remission.

show abstract

Section: Methodssupporting

confidence: 84%

A pharmacokinetic study of Neoral in childhood steroid-dependent nephrotic syndrome

Niaudet¹,

Reigneau

Humbert

2001

Pediatric Nephrology

View full text Add to dashboard Cite

show abstract

“…Table provides the tabulation of the reported C max and AUC values from the various patient studies and healthy subject clinical pharmacology studies reported in the literature . The prediction of AUC values for cyclosporine was performed using the regression equation:

A U C - italiccyclosporine = italicCmax - italicCyclosporine \times 3.9965 prefix+ 384.5

and the appropriate fold differences were computed (Table ).…”

Section: Resultsmentioning

confidence: 99%

Therapeutic drug monitoring of cyclosporine and area under the curve prediction using a single time point strategy: appraisal using peak concentration data

Srinivas¹

2015

Biopharm & Drug Disp

View full text Add to dashboard Cite

There is an ongoing debate on the use of a single concentration time point C2 for therapeutic drug monitoring (TDM) and exposure prediction for cyclosporine. The objective of the present work was to evaluate the relationship between the peak concentration (Cmax ) versus area under the curve (AUC) for cyclosporine. Using published data from renal transplant patients from an 8-12 week study with two formulations, a simple linear regression model represented by AUC - cyclosporine = Cmax - Cyclosporine × 3.9965 + 384.5 (r = 0.9647; p < 0.001) was developed. Using the regression equation, predictions of AUC from the reported Cmax data were performed; the fold difference between observed vs predicted AUC was computed and the root mean square error for the prediction was calculated. While all but one of the predicted AUCs were contained within a 0.5-2-fold difference (99.1%), a greater proportion of the AUC values were predicted within a narrower range of 0.75 to 1.5-fold difference (78.2%), suggesting the utility of Cmax as the right surrogate for predicting the AUC for cyclosporine with a correlation coefficient of 0.8698 (n = 126; p < 0.001) and a RMSE of 26.2%. Since the time to Cmax generally varies from 1 to 2 h, although the results validate the use of C2, there may be an opportunity to explore the suitability of C1 or C1.5 in a prospective study for the purpose of TDM and AUC prediction of cyclosporine.

show abstract

“…The original corn oil formulations of CsA (Sandimmune) have recently been supplanted by a micro-emulsion formulation (Neoral) [5], which seems to demonstrate greater and more consistent bioavailability [5][6][7][8]. The absorption curves of Neoral differ from those of Sandimmune by an earlier and greater peak concentration, namely shorter T max and higher C max [8][9][10]. In addition, in adults the Neoral concentration-time pharmacokinetic (Pk) curves display less inter-and intra-individual variability as compared to Sandimmune [11][12][13][14].…”

Section: Introductionmentioning

confidence: 99%

Reduced variability of Neoral pharmacokinetic studies in pediatric renal transplantation

Portman¹,

Meier-Kriesche²,

Swinford

et al. 2000

Pediatric Nephrology

View full text Add to dashboard Cite

In adult renal transplant recipients the Neoral area under the curve (AUC) displays less inter- and intra-individual variability than Sandimmune, and those renal transplant recipients with reduced intra-individual variability of the AUC have a lower risk for chronic rejection. As variability of Neoral pharmacokinetic (Pk) parameters has not been investigated in pediatric renal transplant recipients, we retrospectively analyzed 453 Pk profiles in 14 pediatric patients who were switched from Sandimmune to Neoral and compared the inter- and intra-individual variability of the Pk profiles on both formulations. After the switch, we observed less inter- and intra-individual variability of AUC, the 2-h concentration, and the oral clearance. As clearance with both formulations is supposedly equal, the significantly lower intra-individual variability of oral clearance is most likely an effect of less variable absorption. While the lower inter-individual variability of the Pk parameters suggests increased success in keeping cyclosporine concentrations on target, the lower intra-individual variability leads to the hypothesis that with Neoral, a lower incidence of chronic rejection might be achieved.

show abstract

Cyclosporin pharmacokinetics following administration of capsules and Neoral in paediatric patients with lupus nephritis

Cited by 11 publications

References 3 publications

A pharmacokinetic study of Neoral in childhood steroid-dependent nephrotic syndrome

A pharmacokinetic study of Neoral in childhood steroid-dependent nephrotic syndrome

Therapeutic drug monitoring of cyclosporine and area under the curve prediction using a single time point strategy: appraisal using peak concentration data

Reduced variability of Neoral pharmacokinetic studies in pediatric renal transplantation

Contact Info

Product

Resources

About