PHARMACOKINETICS OF THE CONVENTIONAL AND MICROEMULSION FORMULATIONS OF CYCLOSPORINE IN PANCREAS-KIDNEY TRANSPLANT RECIPIENTS WITH GASTROPARESIS1

2 hr) was 150% higher after the novel formulation. The coefficient of variation in AUC (0-->2 hr) for both formulations was comparable (37% after the microemulsion and 40% after the standard formulation). The median time at which blood CsA levels exceeded the preceding trough level by 20% was 30 min (range: 30 -> 718 min) after the standard formulation. With approximately the same average dose, the AUCss tau after the microemulsion was 81% higher than the standard formulation, while predose and 12-hr trough levels were similar. The average maximal CsA plasma level after the microemulsion was 396 ng/ml (95% CI: 71-722 ng/ml) higher than after the standard formulation. The median time at which the highest blood levels were observed was 90 min (range: 150 -> 718 min) after the standard formulation. The time profiles of the CsA metabolites followed those of the parent compound. The microemulsion resulted in a higher systemic exposure to CsA than the standard formulation in pancreas-kidney transplant patients with diabetic gastroparesis, but substantial variability in blood concentrations remained. -->
ISSN: 0041-1337
DOI: 10.1097/00007890-199608270-00006
Přístupová URL adresa: https://explore.openaire.eu/search/publication?articleId=doi_________::9d0f6993d3182c9306680792220e86a9
https://doi.org/10.1097/00007890-199608270-00006
Přírůstkové číslo: edsair.doi...........9d0f6993d3182c9306680792220e86a9
Autor: Rik C. Schoemaker, F. J. Van Der Woude, J. Burggraaf, J.W. van der Pijl, Adam F. Cohen, N. Srivastava, J Denouël
Rok vydání: 1996
Předmět:
Zdroj: Transplantation. 62:456-462
ISSN: 0041-1337
DOI: 10.1097/00007890-199608270-00006
Popis: Cyclosporine (CsA) is an immunosuppressive drug requiring dose individualization and regular control due to its highly variable pharmacokinetics. Since gastroparesis may influence the absorption of CsA, a randomized cross-over study was performed to assess the pharmacokinetics and tolerability of a novel microemulsion CsA formulation in comparison with the standard CsA dosage form in six stable pancreas-kidney transplant recipients with scintigraphically proven gastroparesis. The absorption of CsA was investigated during three 2-hr study days during each treatment period, and a full pharmacokinetic profile was done for each formulation. No adverse events or differences in tolerability/safety parameters between the treatments were found. The average AUC (0-->2 hr) was 150% higher after the novel formulation. The coefficient of variation in AUC (0-->2 hr) for both formulations was comparable (37% after the microemulsion and 40% after the standard formulation). The median time at which blood CsA levels exceeded the preceding trough level by 20% was 30 min (range: 30 -> 718 min) after the standard formulation. With approximately the same average dose, the AUCss tau after the microemulsion was 81% higher than the standard formulation, while predose and 12-hr trough levels were similar. The average maximal CsA plasma level after the microemulsion was 396 ng/ml (95% CI: 71-722 ng/ml) higher than after the standard formulation. The median time at which the highest blood levels were observed was 90 min (range: 150 -> 718 min) after the standard formulation. The time profiles of the CsA metabolites followed those of the parent compound. The microemulsion resulted in a higher systemic exposure to CsA than the standard formulation in pancreas-kidney transplant patients with diabetic gastroparesis, but substantial variability in blood concentrations remained.
Databáze: OpenAIRE
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