See references below for related reading.

9.1      Overview of drug dosing problem
9.1.1    Problems of scaling up doses from animal systems
9.1.2    Basing dosing on size, area, weight of recipient
9.1.3    Vast differences between adults in terms of genetics, metabolism
9.1.4    Dosing in children – children are NOT smaller adults!
9.1.5    Pharmacokinetics – drug distribution, metabolism, excretion, breakdown
9.1.6    Conventional dosing assumes drug goes everywhere in the body
9.1.7    Targeted therapies – a model for future nanomedical systems?

9.2      From the animal dosing to human clinical trials
9.2.1    Importance of picking an appropriate animal model system
9.2.2    Does drug dosing really scale?
9.2.3    The human guinea pig in clinical trials and beyond

9.3      Traditional drug dosing methods
9.3.1    Attempts to scale up on basis of area
9.3.2    Attempts to scale up on weight/volume
9.3.3    Attempts to use control engineering principles

9.4      Genetic responses to drug dosing
9.4.1    All humans are not genomically equivalent!
9.4.2    Predicting on basis of family tree responses
9.4.3    SNPs, chips, and beyond…predicting individual drug response
9.4.4    After the $ ???? individual genome scan… more closely tailored individual therapies

9.5      Dosing in the era of directed therapies – a future model for nanomedical systems?
9.5.1    How directed therapies change the dosing equation
9.5.2    Current generation directed antibody therapies dosing
9.5.3    Some typical side effects of directed therapies
9.5.4    Nanomedical systems are the next generation of directed therapies

9.6      Most directed therapies are nonlinear processes!
9.6.1    Meaning of nonlinear processes
9.6.2    Some examples of how a few directed therapies work
9.6.3    Side effects of “directed therapies”

9.7      Other ways of controlling dose locally
9.7.1    Magnetic field release of drugs
9.7.2    Light-triggered release of drugs

Adams, G.P., Weiner, L.M. "Monoclonal Antibody Therapy of Cancer". Nature Biotechnology 23(9): 1147- 1157 (2005)

Baber, N., Pritchard, D. "Dose estimation for children". British Journal of Clinical Pharmacology 56: 489–493, 2003

Bailey, J.M., Haddad, W.M. "Paradigms, Benefits, and Challenges: Drug Dosing Control in Clinical Pharmacology". IEEE Control Systems 35-51, April 2005

McCoy, C.P., Rooney, C., Edwards, C.R., Jones, D.S., Gorman, S.P. "Light-Triggered Molecule-Scale Drug Dosing Devices". Journal of the American Chemical Society 99: 9572-9573, 2007.

Miller, A.A "Body Surface Area in Dosing Anticancer Agents: Scratch the Surface!" Journal of the National Cancer Institute 94(24):1822-1823, 2002

Wajima, T., Yano, Y. Fukumura, K., Oguma, T., "Prediction of Human Pharmacokinetic Profile in Animal Scale Up Based on Normalizing Time Course Profiles". Journal of Pharmaceutical Sciences 93(7):1890 – 1900, 2004

"Targeted Cancer Therapies". National Cancer Institute

Thomas, C.R., Ferris,D.P., Lee,J-H, Choi,E. Cho, M.H., Kim, E.S., Stoddart, J.F., Shin, J-S, Cheon,J., Zink, J.I. “Noninvasive Remote-Controlled Release of Drug Molecules in Vitro Using Magnetic Actuation of Mechanized Nanoparticles” Journal of the American Chemical Society 132: 10623–10625 (2010).

Researchers should cite this work as follows:

• James Leary (2011), "BME 695L Lecture 9: Challenges of Proper Drug Dosing with Nanodelivery Systems ," https://nanohub.org/resources/12262.

  BibTex | EndNote

1. course lecture
2. drug delivery
3. nanomedicine