Raman Venkataramanan, PhD

Raman Venkataramanan, PhD

718 Salk Hall School of Pharmacy
3501 Terrace Street
Pittsburgh, PA 15261

Liver-Related Work

Clinical and Research Interests: I am a basic and clinical pharmacologist. I have 35 years of experience performing preclinical and clinical pharmacological studies. We have developed and validated various assay methods to measure drug levels to personalize drug therapy in different patient populations, through a better understanding of the pharmacokinetics and pharmacodynamics. We currently work with liver, kidney, lung, small bowel, and bone marrow transplant patients and pregnant subjects. Our studies evaluate the metabolic and transport capacity of liver and kidney in these patient populations. Our studies are focused on the impact ischemia and reperfusion injury on liver function; impact of hepatic regeneration on drug metabolizing capacity of the liver; and impact of pregnancy on drug metabolic and transport capacity in patients. We use human hepatocyte cultures (two dimensional and three dimensional cultures) and in vitro hepatic microsomal studies to mechanistically understand regulation of drug metabolism in the liver. Our studies are funded through industrial grants and grants from NICHD and NIH. I also supervise the therapeutic drug monitoring laboratory section in the special chemistry division of UPMC.   
Ongoing Research Studies:
  1. NICHD: Optimization of Drug Dosing in Pregnant Women through research and Education – Impact of Pregnancy on Buprenorphine Pharmacokinetics and Pharmacodynamics – Clinical: This study proposes to address a pressing need in Obstetric Pharmacology related to buprenorphine treatment of opioid-addicted women. This proposal will determine the pharmacokinetics of buprenorphine and determine if there is a better way to gauge dosing based on objective and physiological parameters of satiety. We will also determine which maternal, placental or fetal factors impact the risk of Neonatal Abstinence Syndrome. 
  2. NICHD:  Optimization of Drug Dosing in Pregnant Women through research and Education – Basic/Translational Investigations on Buprenorphine – Basic Science: Our proposed basic/translational studies will complement the clinical study proposed and provide mechanistic information and data that cannot be normally obtained in pregnant women. We will study: (1) the effect of pregnancy on how buprenorphine in metabolized using pregnant rats and isolated livers from pregnant rats; (2) how buprenorphine alters various endogenous chemicals in the brain and hence the response to buprenorphine. Since patients are on chronic therapy with buprenorphine and placenta tends to accumulate a lot of buprenorphine, we will evaluate the impact of buprenorphine on various enzymes and proteins in the placenta of pregnant women on buprenorphine in comparison to those not on buprenorphine. In addition, we will study the ability of the fetal liver to metabolize any buprenorphine that crosses the placenta. We plan to use computer simulations to predict what will happen to exposure of buprenorphine in the mother and fetus at various time points during pregnancy. Collectively our studies will help optimize dosing of buprenorphine in pregnant women and minimize non-adherence to this important treatment option.          
  3. NICHD: Optimization of Drug Dosing in Pregnant Women through research and Education -Feasibility and Safety of Vaginal Administration of 17-hydroxyprogesterone Caproate  – Pilot:  In this pilot study we are proposing to develop and test a vaginal formulation of 17-hydroxyprogesterone caproate (17-OHPC) to prevent preterm delivery. We postulate that the vaginal preparation will be better tolerated than injections and will be as effective if not more so.
  4. NIH: All-Human Microphysical Model of Metastasis Therapy: Successful eradication of metastatic disease remains a challenge in reducing mortality from solid tumors. In this study, we will evaluate the functional capacity of the liver in the presence of cancer cells, by evaluating the metabolic and transporter functions of the hepatocytes.
  5. Industry: Remodulin to prevent I/R injury of liver grafts: In this study we are evaluating the protective effect of Remodulin in minimizing I/R injury of the liver in liver transplant patients.
  6. NICHD-T-32: Training in basic and Clinical Pharmacology in Pregnancy.

Research Service: Our laboratory is equipped to perform in vitro hepatocyte culture work, isolated liver perfusion studies and in vivo animal studies. The special chemistry lab in the CLB (Pathology) supports various research studies. We offer assays for several drugs and vitamins in this lab. We also provide consultation for preclinical and clinical drug study designs. For details please contact me at the email address above.

 

Professor
Pharmaceutical Sciences and Department of Pathology