1967–1978: The Riegelman Chairship
After serving two years as department chair, Jere Goyan, PhD, assumed the deanship of the School of Pharmacy in 1967. Sidney Riegelman, PhD, was named chair of the Department of Pharmacy, serving for 11 years. Riegelman, a world-renowned leader and one of the founders of the discipline of pharmacokinetics, is recognized for creating a pharmacokinetics program considered among the top two or three programs in the world ever since. Building upon the expertise in pharmacokinetics among the faculty members he inherited (Donald Sorby, Berton Ballard, and Thomas Tozer), he recruited his former postdoctoral fellow, Malcolm Rowland, PhD, in 1967 and Leslie Z. Benet, PhD, in 1969 (Benet received his doctorate at UCSF in 1965, under Goyan’s mentorship). In 1973, they founded the first journal in the discipline, the Journal of Pharmacokinetics and Biopharmaceutics (today the Journal of Pharmacokinetics and Pharmacodynamics), with Riegelman as editor and Benet and Rowland as associate editors. Other faculty members with pharmacokinetics training who joined the department under Riegelman’s leadership included Svein Øie, PhD; C. Anthony Hunt, PhD; Betty-ann Hoener, PhD; and Peter Veng-Pedersen, PhD.
Ninth Floor Project: Beginnings of the Clinical Pharmacy program
In 1966, Riegelman, Sorby, and Goyan, together with Chief Pharmacist Owyang, were the senior-level driving forces in establishing a radical experimental program in which pharmacists would optimize therapy outcomes by monitoring the drug therapy of patients on the ninth-floor surgical ward of UCSF Moffitt Hospital. This created an environment in which physicians, nurses, and other health care professionals had the opportunity to discuss drug uses and prescriptions directly with pharmacists.
This was the celebrated Ninth Floor Project—established in conjunction with the departments of surgery and nursing—in which pharmacy students, residents, and faculty members were trained to work at patients’ bedsides to help administer drugs and to become actively involved in treatment decisions. This pilot project set the stage for what became known as the UCSF Clinical Pharmacy Program. The leadership of Department of Pharmacy faculty members provided the clout that allowed the fledgling Division of Clinical Pharmacy to implement its patient-oriented program and to become the world leader in the transformation of pharmacy practice.
As part of this thrust, the department established a clinical pharmacokinetics laboratory in 1974 and recruited Wolfgang Sadee, PhD, to be the director of analytical services. This lab provided measurements of patient samples for narrow therapeutic index drugs (including digoxin and theophylline), facilitating rational adjustments in the dosage regimens of individual patients. Further, the collected bank of data thus generated provided the basis for an innovative case-study course in clinical pharmacokinetics, established by Thomas Tozer and Michael E. Winter, PharmD. Winter served as the director of clinical pharmacokinetic consulting services for the laboratory.
During Riegelman’s tenure as chair, the department formed a close collaboration with the newly created Division of Clinical Pharmacology in the Department of Medicine (under the leadership of Kenneth L. Melmon, MD, and Howard F. Morrelli, MD). Pharmacy faculty members Riegelman, Rowland, Benet, and Tozer held joint appointments in the Division of Clinical Pharmacology, resulting in a large fraction of UCSF Clinical Pharmacology fellows being mentored by Department of Pharmacy faculty members and conducting research studies in their labs. The department also strengthened the Pharmaceutical Technology Laboratory with the recruitment of James E. Tingstad, PhD, from the Upjohn Company (presently Pfizer).
Major departmental scientific contributions (1967–1978)
- Introduced clearance concepts to pharmacokinetics and clinical medicine and defined intrinsic clearance as a parameter distinct from blood flow and protein binding in a model that quantitatively characterized drug elimination.
- Emphasized the necessity of considering multi-compartment pharmacokinetic models to satisfactorily define and predict drug disposition.
- Quantitated the importance of a variety of pathologic and environmental conditions in characterizing the pharmacokinetics of lidocaine and theophylline, requiring drug-dosing modifications to maximize efficacy and minimize toxicity. These early studies served as the template for such analyses.
- Demonstrated the power of physiologically based pharmacokinetic (PBPK) modeling to predict mechanistically the pharmacokinetics of drugs, using lidocaine as an example.
- Predicted hepatic first-pass drug loss following oral dosing using the “well-stirred” and “parallel tube” models of hepatic elimination.
- Published seminal paper on solid dispersions.