Dr. Alan Nies received the BS degree (Chemistry) from Stanford, the MD degree from Harvard, and an Internal Medicine residency at the University of Washington. A Clinical Pharmacology fellowship at the UCSF with Ken Melmon completed his formal training. In San Francisco, Dr. Nies developed an interest in cardiovascular pharmacology. In 1968 he went into the US Army where he was Chief of the section on Clinical Pharmacology at Walter Reed Army Institute of Research where he worked on the development of antimalarial drugs for drug-resistant malaria that was endemic in Viet Nam. The drug mefloquin came out of this program.

In 1970 he joined the Clinical Pharmacology unit at Vanderbilt University that was headed by John Oates. Rising through the ranks from assistant professor to professor at Vanderbilt, Dr. Nies pursued his interest in the clinical pharmacology of the cardiovascular and renal systems. He was particularly interested in the role that the circulation had on pharmacokinetics and particularly how hepatic blood flow influenced a drug’s kinetics. Working with David Shand and later with Bob Branch and Grant Wilkinson, Dr. Nies developed and tested a physiological, clearance-based system of pharmacokinetics that has been extremely useful in understanding and predicting the influence of diseases on kinetics. This effort was greatly aided by the theoretical work of Malcolm Rowland who had been a fellow with Dr. Nies in San Francisco and had published on clearance as a concept in pharmacokinetics. It was during these investigations that the concept of presystemic elimination was developed with propranolol as a model compound. Also the term “intrinsic hepatic clearance” was coined to describe the ability of the liver to metabolize drugs when blood flow was not rate limiting.

Also it was at Vanderbilt that Dr. Nies became introduced to arachidonic acid and its metabolites. Dr. Nies was particularly interested in the cardiovascular and renal implications of this system. Using infusions of arachidonic acid to stimulate prostanoid production and using the non-steroidal antiinflammatory drugs to inhibit prostanoid production, Dr. Nies and colleagues produced evidence that the kidney is particularly vulnerable to changes in this system, particularly when there is volume depletion.

In 1977 Dr. Nies was recruited to head the Division of Clinical Pharmacology at the University of Colorado. The studies on prostaglandins continued with the collaboration of John Gerber. They discovered that prostaglandins were extremely important in modulating the influence of renal vasoconstrictors on the renal blood flow. If the production of prostaglandins was blocked, the vascular effects of norepinephrine, angiotensin and other endogenous vasoconstrictors were markedly enhanced that could result in renal failure. This discovery lead to the understanding of a major adverse effect of the NSAIDs. Additionally, prostaglandin production was found to be of major importance in renal renin production.

Another adverse effect of the NSAIDs was an increase in gastric ulcers. We found that prostaglandins are very important in the stomach to modulate acid production and to couple an increase in gastric acid secretion with an increase in gastric blood flow. Our findings that blocking the production of prostaglandins increased acid production while reducing gastric blood flow gives one explanation for this adverse effect.

In 1992, Dr. Nies was recruited to Merck Research Laboratories to head their Clinical Pharmacology Department. During his 10 years at Merck, Dr. Nies’ responsibility for clinical development increased to include all of clinical research performed worldwide. This experience at a major pharmaceutical company emphasizes the importance of Clinical Pharmacology rigor and expertise in all aspects of clinical drug development. During Dr.Nies’ tenure at Merck, some of the important drugs developed were alendronate (Fosamax), montelukast (Singulair), aprepitant (Emend), ezetemibe (Zetia) and rofecoxib (Vioxx). The work with Vioxx was of particular interest because of the relationship to Dr. Nies’ previous interests with prostaglandins and their influence on gastric and renal function. Early on in its development we established that rofecoxib had no effect gastric prostaglandin synthesis or on platelet function or thromboxane production. However, we were surprised to find that the effects on the kidney were similar to non-selective NSAIDs. Additionally, we found that all COX-2 inhibitors had a major effect on prostacyclin production, which had previously been thought to be under control of COX-1. This raised the possibility that inhibitors selective for COX-2 might disturb the balance at the blood, endothelium interface. Unfortunately, this seems to have been more than a theoretical concern and Vioxx has been withdrawn from the market.

Following his retirement from Merck Research Laboratories, Dr. Nies has been consulting on drug development issues for several companies and has been appointed to the Board of Directors for a Lexicon Genetics, a biotech company in Houston.

During his career, Dr. Nies has participated in many national and international committees and organizations and has received a number of honors including the Harry Gold award and the Oscar B. Hunter award.

Dr. Nies received a PhRMA Foundation Faculty Award in Clinical Pharmacology in 1971.