uu.seUppsala University Publications
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
The pharmacokinetics and pharmacodynamics of clevidipine, a new ultrashort-acting calcium antagonist, in different animal species and man
Uppsala University, Medicinska vetenskapsområdet, Faculty of Pharmacy, Department of Pharmacy.
1999 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Clevidipine is a new ultrashort-acting calcium antagonist of the dihydropyridine type developed for reduction and control of blood pressure in connection with cardiac surgery. The aim of this thesis was to characterise the in vitro hydrolysis rate of clevidipine in different biological matrices and the pharmacokinetics and pharmacodynamics in animal species and various human populations. The data analyses were performed in WinNonlin and PPHARM.

Clevidipine is rapidly metabolised in blood and extravascular tissues to an inactive carboxylic acid. The hydrolysis in human blood seems to be mediated primarily by esterase(s) associated with the red blood cells and is temperature dependent. Both clevidipine and the individual enantiomers are more than 99.5% bound to plasma proteins. In all species studied, clevidipine is a high clearance drug with a small volume of distributionand an extremely short half-life. The initial rapid decline following cessation of clevidipine infusion is mainly due to elimination and the resulting context-sensitive half-time in man is approximately 1 minute regardless of the duration of the infusion. The twofold difference between the clevidipine concentration in arterial and venous blood in man during ongoing infusion demonstrates the importance of taking this arteriovenous difference into account in the PK/PD analysis. The reductions in the ratio of mean arterial blood pressure and heart rate in healthy subjects and essential hypertensive patients are similar, although a more pronounced decrease in blood pressure is observed in the latter population. The reduced clearance during cardiopulmonary bypass is probably related to the lower body temperature during this condition. The initial rapid increase in the arterial blood concentrations and the short equilibrium time between the blood and the biophase suggest that clevidipine can berapidly titrated to the desired effect in cardiac surgical patients in whom acute changes in blood pressure frequently occur.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis , 1999. , 64 p.
Series
Comprehensive Summaries of Uppsala Dissertations from the Faculty of Pharmacy, ISSN 0282-7484 ; 198
Keyword [en]
Pharmacy
Keyword [sv]
FARMACI
National Category
Pharmaceutical Sciences
Research subject
Biopharmaceutics
Identifiers
URN: urn:nbn:se:uu:diva-947ISBN: 91-554-4393-1 (print)OAI: oai:DiVA.org:uu-947DiVA: diva2:173015
Public defence
1999-04-09, lecture hall 842, Uppsala Biomedical Centre, Uppsala, 13:15
Available from: 1999-03-19 Created: 1999-03-19Bibliographically approved

Open Access in DiVA

No full text
Buy this publication >>

By organisation
Department of Pharmacy
Pharmaceutical Sciences

Search outside of DiVA

GoogleGoogle Scholar

isbn
urn-nbn

Altmetric score

isbn
urn-nbn
Total: 588 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf