Amin Rostami-Hodjegan
Netherlands Organisation for Applied Scientific Research
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Featured researches published by Amin Rostami-Hodjegan.
Molecular Pharmaceutics | 2017
Christine Wegler; Fabienne Z. Gaugaz; Tommy B. Andersson; Jacek R. Wiśniewski; Diana Busch; Christian Gröer; Stefan Oswald; Agneta Norén; Frederik Weiss; Helen Hammer; Thomas O. Joos; Oliver Poetz; Brahim Achour; Amin Rostami-Hodjegan; Evita van de Steeg; Heleen M. Wortelboer; Per Artursson
Many different methods are used for mass-spectrometry-based protein quantification in pharmacokinetics and systems pharmacology. It has not been established to what extent the results from these various methods are comparable. Here, we compared six different mass spectrometry-based proteomics methods by measuring the expression of clinically relevant drug transporters and metabolizing enzymes in human liver. Mean protein concentrations were in general quantified to similar levels by methods using whole tissue lysates. Methods using subcellular membrane fractionation gave incomplete enrichment of the proteins. When the enriched proteins were adjusted to levels in whole tissue lysates, they were on average 4-fold lower than those quantified directly in whole tissue lysates. The differences in protein levels were propagated into differences in predictions of hepatic clearance. In conclusion, caution is needed when comparing and applying quantitative proteomics data obtained with different methods, especially since membrane fractionation is common practice for protein quantification used in drug clearance predictions.
DMD Fast Forward. 2011;. | 2011
Brahim Achour; Jill Barber; Amin Rostami-Hodjegan
The cytochrome P450 (P450) family of enzymes is a major player in the metabolism of therapeutic drugs available on the market, and the development of novel drugs has to take into account these enzymes in the fate of new drugs. Testing the pharmacokinetic behavior of new drugs in animals is a common part of the drug development process. Pigs are increasingly used for this purpose because of their similarity of enzymatic pattern to humans. In this study, adult Suffolk White pig liver microsomal samples were analyzed using mass-spectrometry-based techniques to identify and relatively quantify the porcine hepatic P450 enzymes. The total corrected microsomal protein content (milligrams of protein per gram of liver tissue) was estimated at 32.6 and 36.2 mg/g liver tissue in two samples, and the main identified liver P450 subfamilies were CYP1A, CYP2A, CYP2C, CYP2D, CYP2E, and CYP3A. Label-free quantification was performed using the exponentially modified protein abundance index, and the highest abundance enzymes were CYP2A19 at 34% and CYP2D25 at 26% of the total identified drug-metabolizing P450 enzymes. The highest abundance subfamilies were CYP2A (34%), CYP2C (16%), CYP2D (26%), and CYP3A (14%). Moreover, primary sequence alignment was used to identify human homologs of the identified porcine P450s. Porcine CYP1A2 and CYP2E1 were shown to be equivalent to human CYP1A2 and CYP2E1, respectively. Porcine CYP2A19 has the highest sequence homology to human CYP2A6 and CYP2A13, and pig CYP2C33v4 and CYP2C49 are the porcine equivalent of human CYP2C9 and CYP2C18, respectively. Both identified pig CYP3A enzymes (CYP3A29 and CYP39) were highly homologous to CYP3A4/5.
In: Drug Metabolism Discussion Group Meeting; 15 Sep 2010-18 Sep 2010; Canterbury, UK. 2010. | 2010
Brahim Achour; Amin Rostami-Hodjegan; Jill Barber
The Gaskell Birthday Symposium – A Celebration of Mass Spectrometry | 2015
Hajar Al Feteisi; Francesco Lanucara; Jill Barber; Amin Rostami-Hodjegan; Brahim Achour
The 9th International BioMedical Transporters Conference | 2015
Matthew D. Harwood; Brahim Achour; Sibylle Neuhoff; Gordon L Carlson; Geoffrey Warhurst; Amin Rostami-Hodjegan
In: The 24th Population Approach Group in Europe (PAGE) Meeting; 02 Jun 2015-05 Jun 2015; Hersonissos, Crete, Greece. 2015. | 2015
Janak Wedagedera; Khaled Abduljalil; Theresa Cain; Brahim Achour; Shriram M. Pathak; Mike Dunlavey; M Jamei; Amin Rostami-Hodjegan
In: DMDG GMP JOINT MEETING; 22 Oct 2014-24 Oct 2014; Espace St Martin, Paris. 2015. | 2015
Hajar Al Feteisi; Brahim Achour; Jill Barber; Amin Rostami-Hodjegan
In: Certara 2015 Scientific Webinar Series; 18 Feb 2015; Simcyp Ltd., Sheffield. 2015. | 2015
Brahim Achour; Amin Rostami-Hodjegan
14th Human Proteome Organization World Congress | 2015
Brahim Achour; Francesco Lanucara; Hajar Al Feteisi; Jill Barber; Amin Rostami-Hodjegan
In: DMDG and GMP Joint Meeting; 22 Oct 2014-24 Oct 2014; Paris, France. 2014. | 2014
Matthew D. Harwood; Brahim Achour; Yann Courbebaisse; Matthew R. Russell; Sibylle Neuhoff; Gordon L Carlson; Geoffry Warhurst; Amin Rostami-Hodjegan