| Cyclosporine pharmacokinetics and variability from a microemulsion formulation--a multicenter investigation in kidney transplant patients. | |
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MedLine Citation:
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PMID: 7940685 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The steady-state pharmacokinetics and tolerability of a microemulsion formulation of cyclosporine (Sandimmune Neoral) were compared with the commercial formulation (Sandimmune) in 55 clinically stable renal allograft recipients. In study period I (2 weeks' duration), patients entered the study on a stable, individualized twice-daily dosage regimen of the commercial formulation. In period II (2 weeks), they were changed over to the microemulsion formulation at the same dose as at study entry. In period III (2 weeks), dose titration was subsequently allowed if necessary to provide comparable steady-state trough concentrations as at study entry. The commercial formulation was reinstituted during period IV (2 weeks). Safety and tolerability were assessed at weekly clinic visits, and the steady-state pharmacokinetics of cyclosporine in whole blood were characterized at the end of each study period. A milligram-to-milligram dose conversion was adequate when making the initial change between formulations in order to maintain steady-state trough concentrations in the target therapeutic range. Concomitant with this conversion, the steady-state peak concentration and area under the curve increased on average by 59% and 30%, respectively, due to absorption-related differences between the formulations. These increases were not associated with an increase in adverse experiences or changes in blood pressure or clinical laboratory parameters over the first four weeks after the change-over. Trough concentrations were more stable and were more strongly correlated with systemic exposure (area under the curve) during treatment with the microemulsion formulation. Intraindividual coefficients of variation in steady-state peak concentration, time to attain the peak, area under the curve, and percent peak-trough fluctuation ranged from 18% to 74% from the commercial formulation. Variability from the microemulsion formulation was significantly less, ranging from 10% to 22%. |
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Authors:
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J M Kovarik; E A Mueller; J B van Bree; S S Flückiger; H Lange; B Schmidt; W H Boesken; A E Lison; K Kutz |
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Publication Detail:
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Type: Clinical Trial; Comparative Study; Journal Article; Multicenter Study |
Journal Detail:
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Title: Transplantation Volume: 58 ISSN: 0041-1337 ISO Abbreviation: Transplantation Publication Date: 1994 Sep |
Date Detail:
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Created Date: 1994-10-31 Completed Date: 1994-10-31 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 0132144 Medline TA: Transplantation Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 658-63 Citation Subset: IM |
Affiliation:
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Sandoz Pharma, Ltd., Basle, Switzerland. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Absorption Adult Aged Cyclosporine / blood, pharmacokinetics* Drug Tolerance Emulsions Female Graft Survival / drug effects Humans Kidney Transplantation* Male Middle Aged Transplantation, Homologous |
| Chemical | |
Reg. No./Substance:
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0/Emulsions; 59865-13-3/Cyclosporine |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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