title: A simple method for comparing enzymatic capecitabine activation in various mono- and combination chemotherapies.
abstract: Before being able to develop a pharmacodynamic effect, a number of drugs have to be activated by enzymes, which are known to be potentially influenced by manifold factors, leading to a possible alteration of their activity behaviour. Based on capecitabine, we report a simple and rapid method for the estimation and comparison of the so-called 'apparent enzyme activity' (R), not only intra- (different dose levels) but also inter-schedule, to contribute to therapeutic success. Dividing the area under the curve (AUC) of the product by the AUC of the precursor generates a factor which indicates the apparent activity of the enzyme involved in the biotransformation of a compound. Our own data as well as data from the literature was used to calculate those R levels revealing that the formation of 5'-DFUR - the immediate precursor of 5-fluorouracil - was not affected by concomitant medication within the dosing range investigated. Calculated hypothetical means of R for carboxylesterase (1.49 ± 0.66) and for cytidine deaminase (1.17 ± 0.65) were obtained. Additionally, it is important to note that the method described in this report is of general use and not limited to chemotherapeutic agents, as soon as enzymes are involved in drug activation.
authors.affiliation: Division of Clinical Pharmacy and Diagnostics, University of Vienna, Vienna, Austria.
authors.forename: Philipp
authors.initials: P
authors.lastname: Buchner
authors.forename: Azra
authors.initials: A
authors.lastname: Sahmanovic
authors.forename: Veronika
authors.initials: V
authors.lastname: Schreiber
authors.forename: Nairi
authors.initials: N
authors.lastname: Baroian
authors.forename: Christian
authors.initials: C
authors.lastname: Dittrich
authors.forename: Martin
authors.initials: M
authors.lastname: Czejka
mesh_terms: D061067:Antibodies, Monoclonal, Humanized / Q000493:pharmacokinetics; D000970:Antineoplastic Agents / Q000493:pharmacokinetics*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000493:pharmacokinetics; D000068258:Bevacizumab; D002166:Camptothecin / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D000069287:Capecitabine; D043182:Carboxylesterase / Q000378:metabolism*; D003564:Cytidine Deaminase / Q000378:metabolism*; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D004789:Enzyme Activation; D000069347:Erlotinib Hydrochloride; D005472:Fluorouracil / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D006801:Humans; D000077146:Irinotecan; D009944:Organoplatinum Compounds / Q000493:pharmacokinetics; D000077150:Oxaliplatin; D011799:Quinazolines / Q000493:pharmacokinetics
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D011799:Quinazolines; D000077150:Oxaliplatin; D003841:Deoxycytidine; D000068258:Bevacizumab; D000069287:Capecitabine; D000077146:Irinotecan; D000069347:Erlotinib Hydrochloride; D043182:Carboxylesterase; D003564:Cytidine Deaminase; D005472:Fluorouracil; D002166:Camptothecin