Linked Life Data

12803575

Source:http://linkedlifedata.com/resource/pubmed/id/12803575

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2003-6-13
pubmed:abstractText
Cytochrome P450 1A2 (CYP1A2) plays an important role in drug metabolism. Provocation with caffeine is used to estimate CYP1A2 activity, but in most tests a long period of caffeine abstinence has to be taken into account. We compared two novel methods with the currently applied test. The pharmacokinetic (PK) parameters of caffeine and paraxanthine were estimated in eight caffeine-taking healthy volunteers by fitting serum concentration-time data to a two-compartment PK model. Then a three-step approach was followed. Step 1: The caffeine administration regimens of three provocation methods, which differ by their periods of abstinence, together with the PK parameters of each volunteer, were entered in a PK simulation program and the molecular ratio of the paraxanthine/caffeine concentration (P/C molratio) of each method was estimated for the individual volunteers. Step 2: For each method a relationship for the population between the caffeine clearance (Clc) and the corresponding P/C molratio was empirically established. Step 3: The true caffeine clearance (Clc tr) of each volunteer, as found by fitting the individual PK curve, was compared for all three methods with the clearance estimated from the individual P/C molratio using the relationship of step 2. The predictive values for Clc of the three methods did not differ significantly from Clc tr. For the three methods the values for bias were 6.7, 4.3 and 3.1%, respectively and for precision they were 12.3, 20.6 and 17.8%. We conclude that the two novel methods of caffeine provocation show good predictive performance for Clc when compared with the conventional method. Abstaining from caffeine for a long period is not necessary to estimate CYP1A2 activity (using the P/C molratio) accurately.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0767-3981
pubmed:author
pubmed:issnType
Print
pubmed:volume
17
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
355-62
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2003
pubmed:articleTitle
Two novel methods for the determination of CYP1A2 activity using the paraxanthine/caffeine ratio.
pubmed:affiliation
Department of Clinical Pharmacy, Academic Medical Centre, University of Amsterdam, Meibergdreef 9, NL 1105 AZ Amsterdam, The Netherlands.
pubmed:publicationType
Journal Article, Clinical Trial, Comparative Study