Benet L Z and Galeazzi R L: Noncompartmental Determination of the Steady-State Volume of Distribution, J Pharm Sci 68, 1071–1074, 1979—the Backstory

Abstract

In 1967, as a young assistant professor at Washington State University, I received a call from Dr. Arnold Marcus, then the chair of the Industrial Pharmaceutical Technology Section of the Academy of Pharmaceutical Sciences, who asked if I would serve as a faculty member in the academy’s January 1968 Arden House Conference on Pharmacokinetics. I answered, “Arnold, I don’t know any pharmacokinetics. I never took a course in pharmacokinetics and the little reading that I’ve done in the pharmacokinetics literature is just cursory.” Arnold replied that he was looking for someone with a good mathematical background to critique the approaches then being proposed in the field of pharmacokinetics and to lead the discussion during the last session of the course summarizing the positives and negatives of the approaches being employed, while attempting to hypothesize the future directions of the field. I accepted Arnold’s offer and in late January 1968 traveled from Pullman, Washington to Harriman, New York with a suitcase full of Journal of Pharmaceutical Sciences issues containing pharmacokinetic papers. Obviously this was prior to copy machines and baggage fees. I felt that I learned more about pharmacokinetics than any of the attendees at the conference, and my general impression at that time was that the discipline as practiced was much too complicated mathematically (unnecessarily) to have a major impact on drug therapy. In general the pharmacokinetic parameters in use at that time appeared to have no relationship with useful physiological and pathological processes that would allow a clinician to know how to adjust dosing under the various conditions that a patient would experience.