- Overview of drug dosing problem
- Problems of scaling up doses from animal systems
- Basing dosing on size, area, weight of recipient
- Vast differences between adults in terms of genetics, metabolism
- Dosing in children – children are NOT smaller adults!
- Pharmacokinetics – drug distribution, metabolism, excretion, breakdown
- Conventional dosing assumes drug goes everywhere in the body
- Targeted therapies – a model for future nanomedical systems?
- From the animal dosing to human clinical trials
- Importance of picking an appropriate animal model system
- Does drug dosing really scale?
- The human guinea pig in clinical trials and beyond
- Some drug dosing methods
- Attempts to scale up on basis of area
- Attempts to scale up on weight/volume
- Attempts to use control engineering principles
- Genetic responses to drug dosing
- All humans are not genomically equivalent!
- Predicting on basis of family tree responses
- SNPs, chips, and beyond…predicting individual drug response
- After the $ 1000 individual genome scan… more closely tailored individual therapies
- Dosing in the era of directed therapies – a future model for nanomedical systems?
- How directed therapies change the dosing equation
- Current generation directed antibody therapies dosing
- Some typical side effects of directed therapies
- Nanomedical systems are the next generation of directed therapies
- Most directed therapies are nonlinear processes
- Current and pending FDA approved directed therapies
- Some examples of how a few directed therapies work
- Complement directed cytotoxicity
- ADCC-mediated adaptive immunity switch
- Antibody-directed enzyme producing therapy
- Other ways of controlling dose locally
- Magnetic field release of drugs
- Light-triggered release of drugs
- Adams, G.P., Weiner, L.M. Monoclonal Antibody Therapy of Cancer. Nature Biotechnology 23(9): 1147- 1157 (2005)
- 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. J. AM. CHEM. SOC. 2007, 129, 9572-9573
- Miller, A.A Body Surface Area in Dosing Anticancer Agents: Scratch the Surface! Journal of the National Cancer Institute, Vol. 94, No. 24, December 18, 2002
- Nigel Baber & Deborah Pritchard Dose estimation for children. Br J Clin Pharmacol 56 , 489–493 2003
Researchers should cite this work as follows:
James Leary (2007), "BME 695N Lecture 14: Challenges of proper drug dosing with nanodelivery systems," https://nanohub.org/resources/3466.
Biomedical Engineering, Room 1083