The mission of the PBL is to implement clinical pharmacology principles and pharmacometrics in academic settings to support drug discovery, drug development and regulatory decisions.

 At PBL we investigate an array of underlying factors that impact drug pharmacokinetics, drug development and drug therapy optimization via employing in vitro, in vivo, in silico and translational approaches.

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PBL was established  in 1986 and is currently located on the 4th floor of a brand new Pharmacy Hall North building (PHN 406, approx. 600 sq. ft within an open floor plan lab). The laboratory is fully equipped with State-of-the-art equipments to perform bioanalysis of drugs in various biological matrices. It includes four fully automated UPLC systems and three HPLC systems with UV and FL detectors. It is well versed in data analysis techniques including pharmacokinetic modeling, physiological based-pharmacokinetic modeling, PK-PD modeling, population PK analyses, simulation analyses and IVIVC modeling. The lab is connected to additional three specialty rooms; a) animal procedure room, room 420, 200 sq. ft. This room is equipped with all necessary equipments to conduct PK experiments (e.g., CO2 tanks, two guillotines, surgical instruments, analytical balance, animal weighing balance and desiccators), b) Cell culture room, N418, 200 sq. ft and, c) GLP room, N416, 200 sq. ft. The GLP room includes UPLC Waters qualified system with both UV and FL detector, Mettler Toledo XS105 dual range analytical balance and a pH meter. The lab also includes two gel electrophoresis systems, two -80ºC freezer, three -20ºC freezer, two Beckman coulter bench top centrifuges, two power homogenizers, two Branson sonicators, DVX-2500 multitube vortexer, Multivap nitrogen evaporator, OHAUS Adventure Pro analytical balance, Denver analytical balance, DS-500 orbital shaker, VWR rocking platform, four VWR analog vortex mixers, UGO basil tail flick apparatus, Milli-Q Advantage A10 system (Millipore), two VWR hotplate stirrers, Metler Toledo pH meter, VWR heat block, ~70 HPLC/UPLC functioning columns, Bio-Rad Econo Pump, 40 calibrated pipets including electronic eppendorf repeater Xstream pipet and electronic eppendorf research pro multichannel pipet, Sanyo incubator and Beckman DV 640 spectrophotometer.

RESEARCH PROJECTS

I. Drugs of Abuse/Pain medications

  • Project 1. Investigate the influence of heat on drug release kinetics from Fentanyl and Nicotine transdermal drug delivery systems (TDS) in humans: Development of IVIVC models (FDA – Funded)

  • Project 2. Investigate metabolism/transporters-mediated pharmacokinetic drug-drug interactions among drugs of abuse and anticancer agents

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  • Project 3. Evaluate the absolute bioavailability/PK and residual drug analysis of fentanyl TDS in humans (FDA/NIPTE- Funded)

 

  • Project 4. Identify chemical enhancer specification requirements for fentanyl TDS (FDA/NIPTE – Funded)

 

  • Project 5: Development of L-THP for management of cocaine addiction: Phase IIa study (NIH – Funded)

 

 

 

 

  • Project 6. Evaluate the bioequivalence of topical FDA approved products in humans using dermato-pharmacokinetic approach (FDA – Funded)

II. Anti-infectives

  • Project 7. Evaluate the dose needed to Achieve Vancomycin AUC/MIC >400 in critically-Ill pediatric patients: Population PK study (NIH – Funded)

 

  • Project 8. Evaluate Meropenem dosage regimens in pediatrics

 

 

  • Project 9. Evaluate Azithromycin to prevent bronco-pulmonary dysplasia PD in Ureaplasma-infected preterm neonates: Population PK study (NIH – Funded)

 

 

 Project Highlight (Project # 2)

 

Drug-transporters

Efflux and Influx Drug Transporters

The majority of the clinically significant drug-drug interactions (DDIs) occur via induction or inhibition of drug metabolizing enzymes (DMEs) and drug transporters (DTs), where perturbation of DMEs and DTs by one agent leads to changes in the systemic exposure and clearance of another and hence affects its therapeutic/toxic level. A large emphasis of my research is devoted to unraveling the role of disposition-controlling genes [e.g., xenobiotic receptors (XRs), DTs and DMEs in mediating PK, pharmacodynamics (PD) and drug-drug interactions (DDIs) of novel and commonly used therapeutic agents especially opioids. Identifying the complete expression spectrum of disposition-controlling genes upon repeated administration of opioids would provide scientific explanations for the staggering number of opioid-related DDIs and would help in optimizing therapeutic doses of concomitantly administered therapeutic agents. We successfully demonstrated that repeated administration of the highly abused opioid, oxycodone, induced a wide array of XRs, DMEs and DTs in various tissues. Expanding on these findings, we are currently studying the impact of these changes on the PK of commonly co-administered therapeutic agents (e.g., anticancer agents, antiretroviral agents). And, we are augmenting this with employing gene mapping analysis to determine signature gene-network for each opioid which not only identify the type of interaction among genes but also identify XRs and transcription factors that are involved in drugs of abuse-mediated induction/suppression of DMEs and DTs. Positive outcome of our research will help in adjusting therapeutic doses and avoiding untoward DDIs.

 

Professional Platforms at PBL

PBL has more than 15 workstations loaded with a number of platforms that are necessary for PK data analyses, statistical analyses, data integration and representation including Nonmem, Phoenix NLME, R, ADAPT5, GraphPad Prism, SigmaPlot, Pirana, Census and Endnote.

 

Main Equipments at PBL

  1. Four fully automated UPLC systems with UV and FL detectors

  2. Three HPLC systems with UV and FL detectors

  3. Four Forma incubators for cell culture work

  4. Two biosafety hoods

  5. Two Nikon TMS inverted microscope

  6. Refrigerated desktop centrifuges

  7. Bio-Rad TC10 automated cell counter

  8. Liquid nitrogen tank with temperature monitor.

  9. Mettler Toledo XS105 dual range analytical balance

  10. Mettler pH meter.

  11. Two gel electrophoresis systems

  12. Two -80ºC freezer

  13. Three -20ºC freezer

  14. Two Beckman coulter bench top centrifuges

  15. Two power homogenizers

  16. Two Branson sonicators

  17. Multivap nitrogen evaporator

  18. Milli-Q Advantage A10 system (Millipore)

  19. Beckman DV 640 spectrophotometer.