Improving the ex vivo stability of drug ester compounds in rat and dog serum: Inhibition of the specific esterases and implications on their identity |
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| Authors: | Matthias Koitka,Joachim Hö chel,Hille Gieschen,Hans-Hubert Borchert |
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| Affiliation: | 1. INSERM U850, Université de Limoges, Faculté de Médecine, 2 rue du Dr Marcland, 87025 Limoges, France;2. Bayer Schering Pharma AG, Drug Metabolism and Pharmacokinetics, Muellerstrasse 170-178, 13342 Berlin, Germany;3. Freie Universität Berlin, Institut für Pharmazie, Kelchstrasse 31, 12169 Berlin, Germany |
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| Abstract: | ![]()
In drug development, it has been noticed that some drug compounds, especially esters, are unstable in serum samples ex vivo. This can lead to a substantial underestimation of the actual drug concentration. |
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| Keywords: | α2M, α2-macroglobulin AC, affinity chromatography AChE, acetylcholinesterase ACN, acetonitrile albumin-AC, affinity chromatography for removal of albumin APMSF, 4-amidinophenylmethanesulfonyl fluoride hydrochloride BCA, bicinchoninic acid BChE, butyrylcholinesterase BNPP, bis(p-nitrophenyl) phosphate sodium salt CaCl2, calcium dichloride dihydrate cDNA, complementary deoxyribonucleic acid CE, carboxylesterase ChE, cholinesterase EDTA, ethylenediamine tetraacetic acid disodium salt dihydrate EGTA, ethyleneglycol-bis(2-aminoethylether)-tetraacetic acid IEC, anion-exchange chromatography irinotecan, 7-ethyl-10-[4-(1-piperidino)-1-piperidino]carbonyloxycamptothecin, also referred to as CPT-11 LC-ESI-MS, liquid chromatography&ndash electrospray ionization&ndash mass spectrometry MALDI-TOF-MS, matrix-assisted laser desorption ionization&ndash time of flight&ndash mass spectrometry MPA, methylprednisolone aceponate NaCl, sodium chloride NaF, sodium fluoride NCBI, National Center for Biotechnology Information (Bethesda, USA) NPA, 4-nitrophenyl acetate PAF-AH, platelet-activating factor acetylhydrolase PCR, polymerase chain reaction Pefabloc® SC, 4-(2-aminoethyl-)benzenesulfonyl fluoride hydrochloride PON, paraoxonase PON-AC, affinity chromatography for isolation of PON1-containing fractions SDS-PAGE, sodium dodecyl sulfate-polyacrylamide gel electrophoresis SEC, size-exclusion chromatography TBA, tetrabutylammonium bromide TBS, Tris buffered saline TFA, trifluoroacetic acid TLCK, N-α-tosyl-l-lysine chloromethylketone hydrochloride Tris, tris(hydroxymethyl)aminomethane Tris&ndash HCl, tris(hydroxymethyl)aminomethane hydrochloride UV&ndash vis, ultraviolet&ndash visible spectroscopy |
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