Deepak Ahire et al. published, “Ultrasensitive quantification of drug-metabolizing enzymes and transporters in small sample volume by microflow LC-MS/MS” in the Journal of Pharmaceutical Sciences on 27th March 2021.
We developed an ultrasensitive method that relies on an optimized sample preparation approach involving acetone precipitation coupled with a microflow-based liquid chromatography-tandem mass spectrometry (μLCMS/ MS) for the DMET quantification using limited sample volume or protein concentration, i.e., liver tissues (1-100 mg), hepatocyte counts (~4000 to 1 million cells), and microsomal protein concentration (0.01-1 mg/ml). The method was applied to quantify DMETs in differential tissue S9 fractions (liver, intestine, kidney, lung, and heart) and cryopreserved human intestinal mucosa (i.e., CHIM). The method successfully quantified >75% of the target DMETs in the trypsin digests of 1 mg tissue homogenate, 15,000 hepatocytes, and 0.06 mg/ml microsomal protein concentration.
Revathi Chapa et al. published, ”Contribution of Uptake and Efflux Transporters to Oral Pharmacokinetics of Furosemide” in ACS Omega on 15th December 2020.
Furosemide tablet formulation exhibits variable pharmacokinetics (PK) with bioavailability ranging from 10 to almost 100%. To explain the variable absorption, we integrated the physicochemical, in vitro dissolution, permeability, distribution, and the elimination parameters of furosemide in a physiologically-based pharmacokinetic (PBPK) model.
Siavosh Naji-Talakar et al. published, “Potential implications of DMET ontogeny on the disposition of commonly prescribed drugs in neonatal and pediatric intensive care units” in Expert Opinion on Drug Metabolism & Toxicology on 1st December 2020.
We reviewed the top 29 small molecule drugs prescribed in neonatal and pediatric intensive care units and compiled the mechanisms of their metabolism and excretion. The ontogeny of Phase I and II drug-metabolizing enzymes and transporters (DMETs), particularly relevant to these drugs, are summarized. The potential effects of DMET ontogeny on the metabolism and excretion of the top pediatric drugs were predicted. The current regulatory requirements and recommendations regarding the safe and effective use of drugs in children are discussed. A few representative examples of the use of ontogeny-informed physiologically-based pharmacokinetic (PBPK) models are highlighted.
Sheena Sharma, Deepak Ahire and Bhagwat Prasad published, “Utility of Quantitative Proteomics for Enhancing the Predictive Ability of PBPK Models Across Disease States”, in the Journal of Clinical Pharmacology on 7th November 2020.
we summarized these data including the available immunoquantification or mRNA levels of DMET proteins (healthy vs disease states) in extrahepatic tissue and discuss the potential applications of DMET abundance data in enhancing the capability of PBPK modeling in predicting drug disposition across disease states. Successful examples of PBPK modeling that integrate differences in DMET proteins between healthy and disease states are discussed.
Congratulations to Nandini Katti for receiving funding from the American College of Clinical Pharmacy Foundation Futures Grants Program for a research project titled, “Association of steroidal urinary metabolites in adolescent polycystic ovary syndrome”.
Abdul Basit et al. published, “Characterization of Differential Tissue Abundance of Major Non-CYP Enzymes in Human“, in Molecular Pharmaceutics on 21st September 2020.
The protein abundances of eighteen non-CYP DMEs (AO, CES1 and 2, ten UGTs, and five SULTs) were quantified across five different human tissues. These differential tissue abundance data can be integrated into physiologically based pharmacokinetic (PBPK) models for the prediction of non-CYP drug metabolism and toxicity in hepatic and extrahepatic tissues.
Haeyoung Zhang, Abdul Basit and Bhagwat Prasad published a book chapter, “Quantifying drug metabolizing enzymes and transporters by LC-MS/MS proteomics” in July 2020.
Book title: Identification and Quantification of Drugs, Metabolites, Drug Metabolizing Enzymes, and Transporters. https://www.sciencedirect.com/book/9780128200186/identification-and-quantification-of-drugs-metabolites-drug-metabolizing-enzymes-and-transporters
Prasad lab members think working from home can’t make them any less productive
Yes, COVID-19 cannot affect our determination to pursue our training, teaching, and research!
Prasad lab initiates COVID-19 Research Collaboration
Anyone interested in a collaboration, please contact Bhagwat Prasad.
PRINCE teleconference meeting held in Prasad lab, WSU Spokane on March 27
The meeting discussed PRINCE 2.0 project with collaborators from Genentech, Gilead, and Merck in a teleconference meeting on March 27.
Prasad lab welcomes Dr Vijay Mettu as a new Research Associate!
Dr Mettu has an experience of 15 years of working in drug discovery programs, and in vitro and in vivo DMPK studies. Previous to joining Prasad lab in WSU Spokane, he has worked as an in vivo lead and DMPK program representative in GlaxoSmithKline Singapore and DMPK manager in Agency for Science, Technology and Research (A*STAR), Singapore.
2020 GRSA Science Bites-3 min Thesis Competition Winner
Sheena Sharma won second prize in the WSU Graduate Research Student Association (GRSA) 2020 3-minute thesis competition. Congrats!
2020 WSU Pharm Sci Best Poster Award
Dr Abdul Basit earned the best poster award in the WSU Pharm Sci poster presentation. Kudos!
The Prasad lab wishes everyone very happy holidays 2019!
Picture courtesy: Dr Abdul Basit
Dr Prasad presented a talk on ‘Quantitative Proteomics in Precision Medicine’ in Pharmacology 2019 meeting, Edinburgh UK (Dec 11-17)
The presentation was held in the session entitled ASPET/BPS Joint Symposium on Precision Medicine: Progress and Challenges.
PRINCE teleconference meeting held in Prasad lab, WSU Spokane on Dec 3
The meeting discussed project progress and specific aims for the coming year with collaborators from Genentech, Gilead and Merck.
Prasad lab research on precision medicine for children got featured in the WSU post
The article talked about the importance of finding the precise dosing for pediatric population to avoid toxicity concerns.
Dr Prasad addressed PharmD and PhD students in an interactive talk on ‘Revolutionizing pharmaceutical development with physiologically based pharmacokinetic systems’ at WSU Spokane
Dr Prasad talked about the emerging importance of PBPK in regulatory submissions and pharmaceutical drug development. The students were motivated to pursue unconventional pharmacy jobs in the future to fill the global need for better health care options.
Prasad lab welcomes Dr Masud Parvez as a new Research Associate!
Dr Parvez has a good experience of working on projects related to transport assays and the prediction of pharmacokinetics in special populations using PBPK modeling. Previous to this, he has worked in Shin lab as a Research Assistant Professor at INJE University, Busan, South Korea.
Dr Prasad presented a talk on ‘Role of UGTs and drug transporters in testosterone disposition’ in the first annual symposium on Development, Disease and Reproduction at Center for Reproductive Biology, WSU Pullman
During this oral presentation, Dr Prasad talked about testosterone homeostasis in the human body.
Dr Prasad presented a webinar on ‘Importance of Quantitative Traning to Address Rigor and Reproducibility in DMPK/PD Research’ in the ISSX Webinar Series
In this webinar, Dr Prasad shared why quantitative training is important for different areas of DMPK/PD discipline through case studies. Particularly, examples justifying how the lack of clear understanding of quantitative methods can affect rigor in DMPK/PD research were illustrated to the attendees.
Successful inauguration of LC-MS facility in Prasad lab
The lab has initiated the facility for LC-MS analysis. Waters Xevo-TQ-XS MS with IonKey source and microflow LC will be used to perform targeted proteomics and metabolomics analysis of DMET proteins and biomarkers. Thermo’s Q-Exactive-HF MS with nano-flow LC will be utilized for untargeted proteomics and metabolomics analysis.
Prasad lab moved to WSU, Spokane, WA
Prasad lab has moved to the College of Pharmacy and Pharmaceutical Sciences (CPPS) at Washington State University, Spokane, WA from the University of Washington, Seattle, WA in 2019. The lab is continuing research projects focusing on prediction of drug disposition using omics-informed PBPK modeling approach.
Prasad lab got featured in the cover page of August 2019 issue of Drug Metabolism and Disposition journal
The featured article talks about kidney cortical transporter expression across species using quantitative proteomics.
PRINCE (Proteomics-based Research Initiative on Non-CYP enzymes) consortium sponsored by Genentech, Gilead and Merck started in WSU
The PRINCE (Proteomics-based Research Initiative for Non-CYP Enzymes) program is a research collaboration between the Prasad lab at Washington State University and the pharmaceutical industry to elucidate role of non-cytochrome P450 (non-CYP) enzymes in disposition, efficacy and toxicity of drugs.
Prasad lab received funding from Bristol Myers Squibb (BMS) on the characterization of mARC (mitochondrial amidoxime reducing complex) protein component
The “mitochondrial Amidoxime Reducing Component” (mARC) is the newly discovered fourth molybdenum enzyme in mammals and is involved in reduction of many N-hydroxylated nucleobases and nucleosides and in lipid metabolism.
Members from Prasad lab brought laurels at 12th International ISSX Meeting, held in Portland, OR (July 28–31)
The award recipients from Prasad lab were:
• First place: Haeyoung Zhang for the poster entitled “Is urinary testosterone glucuronide a potential biomarker for UGT2B17 ontogeny in ages 7 to 18 years?”
• Second place: Revathi Chapa for the poster entitled “Investigating the role of drug transporters in furosemide absorption, food-effect and elimination using a proteomics informed-mechanistic PBPK modeling approach.”
• First place: Naveen Neradugomma and Abdul Basit for the poster entitled “Characterization of differential tissue abundance of major non-CYP enzymes in human.”