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Population pharmacokinetic approach to compare oral and i.v. administration of etoposide

by: G. Würthwein, S. Krümpelmann, B. Tillmann, E. Real, P. Schulze-Westhoff, H. Jürgens, and J. Boos

In: Anti-cancer drugs, Vol. 10, Nr. 9 (1999) , p. 807-814.

Abstract

The antitumor effect of etoposide ETO may be related to duration of exposure to a relatively low serum level while myelosuppression may be dependent on peak ETO serum levels. With regard to such therapeutic ranges, duration of exposure to predefined plasma ETO concentration ranges and the related AUC expressed as percent of total AUC, pAUC were used to compare pharmacokinetic profiles after oral and short time i.v. 1 h infusion administration of identical ETO doses 100 mg/m2. Patients included in this study received i.v. 18 patients, short-term infusions or oral 16 patients ETO on different treatment schedules. Plasma ETO concentrations were determined by HPLC and population pharmacokinetic parameters were calculated P-Pharm 1.4. Despite an 'apparent bioavailability' of 59%, oral administration of ETO was associated with the same time of exposure to a predefined 'therapeutic range' of 0.5-3 mg/l and a significantly higher pAUC compared to i.v. administration. By contrast,

BibTeX record

@article{Wurthwein.1999,
  abstract = {The antitumor effect of etoposide (ETO) may be related to duration of exposure to a relatively low serum level while myelosuppression may be dependent on peak ETO serum levels. With regard to such therapeutic ranges, duration of exposure to predefined plasma ETO concentration ranges and the related AUC (expressed as percent of total AUC, pAUC) were used to compare pharmacokinetic profiles after oral and short time i.v. (1 h infusion) administration of identical ETO doses (100 mg/m2). Patients included in this study received i.v. (18 patients, short-term infusions) or oral (16 patients) ETO on different treatment schedules. Plasma ETO concentrations were determined by HPLC and population pharmacokinetic parameters were calculated (P-Pharm 1.4). Despite an 'apparent bioavailability' of 59%, oral administration of ETO was associated with the same time of exposure to a predefined 'therapeutic range' of 0.5-3 mg/l and a significantly higher pAUC compared to i.v. administration. By contrast,},
  added-at = {2010-02-04T16:31:48.000+0100},
  author = {Würthwein, G. and Krümpelmann, S. and Tillmann, B. and Real, E. and Schulze-Westhoff, P. and Jürgens, H. and Boos, J.},
  biburl = {http://www.bibsonomy.org/bibtex/2ce7d51dbbb2a118c3a802a51be590fc1/hruehs},
  interhash = {d7a8d33ae49b7507e6fb2945ffb11ff4},
  intrahash = {ce7d51dbbb2a118c3a802a51be590fc1},
  issn = {0959-4973},
  journal = {Anti-cancer drugs},
  keywords = {& Administration, Adolescent Adult Aged Agents, Antineoplastic Area Availability Biological Child Child, Chromatography, Curve Dose-Response Drug Etoposideadministration Factors Female High Humans Infant Infusions, Intravenous Liquid Male Middle Oral Phytogenicadministration Preschool Pressure Relationship, Time Under dosagebloodpharmacokinetics},
  number = 9,
  pages = {807-814},
  timestamp = {2010-02-04T16:31:48.000+0100},
  title = {Population pharmacokinetic approach to compare oral and i.v. administration of etoposide},
  volume = 10,
  year = 1999
}

Endnote record

%0 Journal Article
%1 Wurthwein.1999
%A Würthwein, G.
%A Krümpelmann, S.
%A Tillmann, B.
%A Real, E.
%A Schulze-Westhoff, P.
%A Jürgens, H.
%A Boos, J.
%D 1999
%J Anti-cancer drugs
%K 
%N 9
%P 807-814
%T Population pharmacokinetic approach to compare oral and i.v. administration of etoposide
%V 10
%X The antitumor effect of etoposide (ETO) may be related to duration of exposure to a relatively low serum level while myelosuppression may be dependent on peak ETO serum levels. With regard to such therapeutic ranges, duration of exposure to predefined plasma ETO concentration ranges and the related AUC (expressed as percent of total AUC, pAUC) were used to compare pharmacokinetic profiles after oral and short time i.v. (1 h infusion) administration of identical ETO doses (100 mg/m2). Patients included in this study received i.v. (18 patients, short-term infusions) or oral (16 patients) ETO on different treatment schedules. Plasma ETO concentrations were determined by HPLC and population pharmacokinetic parameters were calculated (P-Pharm 1.4). Despite an 'apparent bioavailability' of 59%, oral administration of ETO was associated with the same time of exposure to a predefined 'therapeutic range' of 0.5-3 mg/l and a significantly higher pAUC compared to i.v. administration. By contrast,