Library

X
feed icon rss

Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
Filter
  • Pharmacokinetics  (1)
  • drug metabolism  (1)
  • 1
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of carboplatin administered in combination with the bradykinin agonist Cereport (RMP-7) for the treatment of brain tumours (2000)
    Springer
    Cancer chemotherapy and pharmacology 45 (2000), S. 284-290 
    Details
    ISSN: 1432-0843
    Keywords: Key words Carboplatin ; Pharmacokinetics ; Cereport ; Clinical ; Brain tumour
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Introduction: Cereport (RMP-7) is a novel bradykinin agonist which is being developed as a modulator of the blood–brain barrier (BBB). In order to investigate the pharmacokinetics of carboplatin in combination with Cereport, we performed pharmacological studies in conjunction with early clinical trials. Methods: Pharmacokinetic samples were collected from eight patients in a phase I study (Cereport 100–300 ng/kg) and ten patients in a phase II study (Cereport 300 ng/kg). Pharmacokinetic parameters for carboplatin were compared with respect to the dose of Cereport and with historical controls. Results: Cereport combined with carboplatin was well-tolerated, with mild haematological toxicities consistent with the target area under the concentration–time curve (AUC) of 7 mg/ml*min. Although the clearance of carboplatin was within the range reported for this drug alone, the addition of Cereport resulted in a higher than expected carboplatin AUC. This effect was related to the dose of Cereport in the phase I study (AUC values 104–133% of target, Spearman rank correlation coefficient=0.71, P 〈 0.001). The higher than expected AUC value was confirmed in the phase II study (AUC values 106–189% of target). Conclusions: Co-administration of Cereport with carboplatin may result in a greater than predicted AUC. The mechanism of this possible interaction remains to be determined, although this did not result in any increased toxicity. Thus, the clinical potential of this combination in the treatment of brain tumours warrants further investigation.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002800050042
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 2
    Electronic Resource
    Electronic Resource
    Stereoselectivity in Pharmacokinetics: A General Theory (1991)
    Springer
    Pharmaceutical research 8 (1991), S. 551-556 
    Details
    ISSN: 1573-904X
    Keywords: stereoselectivity ; chirality ; enantiomers ; drug metabolism ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Stereoselectivity in pharmacokinetics may be characterized by a measurable difference between enantiomers in a pharmacokinetic parameter. We propose that pharmacokinetic parameters may be classified according to three levels of organization in the body and that the hybrid character of parameters increases with the level of organization that they represent. At the molecular level are intrinsic metabolite formation clearances and fraction of drug unbound in plasma, reflecting the selectivity of an endogenous macromolecule for the enantiomers of a chiral drug molecule. At the organ level, pharmacokinetic parameters represent the combined effects of stereoselectivity in each of their component parameters within an organ. As a result, these parameters are of intermediate hybrid character. Parameters with the highest degree of hybrid character describe the pharmacokinetic behavior of a drug in the whole body. The stereoselectivity associated with each of the component parameters could either amplify or dampen the resultant stereoselectivity in hybrid parameters. The hypothesis that kinetic differences between enantiomers are inversely correlated with the degree of hybrid character was examined for four drugs: warfarin, verapamil, mephenytoin, and propranolol. By classifying pharmacokinetic parameters according to both the level of organization that they characterize and their hybrid nature, it becomes possible to account for stereoselectivity in drug distribution and elimination.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1015884102663
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...