The Development of the Human Pharmacology Lab–By Peter S.A. Glass, MB, ChB

Peter S.A. Glass, MB, ChBThe 15 years that I spent at Duke hold very special memories for me. I was blessed to have many incredible mentors and the support of a wonderful department and institution. It was an exciting time, and countless new drugs were being introduced in perioperative medicine.

Shortly after my arrival in August of 1984, newly appointed chair Dr. W. David Watkins, persuaded me to perform Phase IV studies on the new drug, alfentanil, by Janssen. While leading this study, I worked closely with chief of the Division of Cardiovascular Anesthesia, Dr. Jerry Reves, and a postgraduate student working closely with him named Dr. James “Jim” Jacobs to utilize a new technology called CACI (Computer Assisted Continuous Infusion) to administer alfentanil.

After completion of the Phase IV alfentanil protocols, Jerry and another close friend and mentor in the department, Dr. Enrico Camporesi, encouraged me to perform a Phase I protocol for a new opiate compound developed by Anaquest. Since it was a Phase I study, we would need a dedicated space where we could conduct human volunteer experiments. The department had access to a significant amount of space in Duke South that had been included as part of Dr. Watkins’ recruitment package. In this space existed a large library, which, after some negotiations, was equipped to become the first Human Pharmacology Laboratory (HPL).

The funding obtained from Anaquest allowed me to hire my first research assistant, Dr. David Shafron. David Martel, who was already on the research staff, also played a vital role. This turned out to be an excellent Phase I study, giving us the ability to accurately identify and describe the initial pharmacokinetics and pharmacodynamics of the compound. Subsequently, Anaquest provided us with other compounds to test for potential clinical value, and several of them were introduced into our model.

Unfortunately, Anaquest never introduced any of their opiate compounds into clinical practice, but through these studies, we dramatically improved our techniques of assessing analgesia and pioneered new technology. The HPL became quite active, and numerous faculty, residents, research assistants, and even visiting faculty joined the group. Shortly thereafter, the HPL became an important site for the development of remifentanil—the lead compound developed by Glaxo, which had its U.S. headquarters in the Research Triangle Park. In fact, the first human administration of this compound took place in Duke Anesthesiology’s HPL.

Grants for these studies helped fund several other clinical pharmacology studies of pharmacokinetic and pharmacodynamic principles, including an important one on the context sensitive half-time, a concept proposed by Dr. Jim Jacobs and myself. Furthermore, this is where we first demonstrated that the bispectral index provided a measure of sedation and loss of consciousness rather than being a measure of anesthesia. Finally, studies in the HPL demonstrated how noxious stimuli would increase the bispectral index value during sedation. This could then be ablated by the administration of opiates, thereby helping to define how the interaction between opiate and sedative provides the state of anesthesia.

A few years before I left Duke in 1999, the clinical research unit was moved into an area in Duke South and Dr. Jacques Somma took over what is now referred to as the HPL II. Under Jacques, the HPL continued to be productive, publishing two important studies on remifentanil and dexmedetomidine. The HPL was instrumental in developing my own career, as well as the careers of many others at Duke who shared my interest in biological and medical sciences. At the same time, it helped develop new compounds and many
important new concepts in pharmacokinetics and pharmacodynamics that we incorporate into the practice of anesthesia and drug delivery today.

Chris KeithThe Development of the Human Pharmacology Lab–By Peter S.A. Glass, MB, ChB