1. U N I V E R S I T Y O F K E N T U C K Y - C O L L E G E O F P H A R M A C Y Pharmacokinetics & Drug Transport Philip E. Empey, Pharm.D., Ph.D., BCPS Assistant Professor, Department of Pharmacy and Therapeutics 805 Salk Hall, School of Pharmacy University of Pittsburgh

2. Pharmacokinetics  The study of the time course of a drug in the body and the biological and chemical processes affecting absorption, distribution, metabolism, and excretion.

3. Drug concentration in blood Time

4. Liver Systemic Circulation Tissues Kidney Metabolism DistributionAbsorption Excretion GI Pharmacokinetics: ADME

5. Drug Absorption http://www.nlm.nih.gov/medlineplus/

6. Drug Absorption

7. Absorption Transport Processes ATP H+H+ H+H+ H+H+ H+H+ H+H+ H+H+ H+H+ H+H+ H+H+ FacilitatedActive Passive

8. Absorption Transport Proteins

9. Liver Systemic Circulation Tissues Kidney Metabolism DistributionAbsorption Excretion GI Pharmacokinetics

10. Transport proteins in other organs  Some drugs are transported, some act to inhibit these processes leading to drug interactions! Penicillin/probenecid & quinidine/digoxin  Some physiological conditions or diseases change transporter gene expression

11. Breast Physiology Modified from Breastfeeding (1994) by RA Lawrence

12. [PE1] Need to fix axis Transporters in breast barrier cells Transporters upregulated during lactation Transporters expressed in LMECs at a level similar or greater than other secretory tissues 10* 7 Transporters upregulated during lactation

13. US breastfeeding trends Ryan, et al. 2002 Ross Labs (Abbott) Breastfeeding Statistics

15. Information for prescription drugs? All Marketed Drugs n = 1625

16. Research techniques  Collect breast milk, measure transporter gene expression.  Compare drug concentrations in milk and blood in humans and animals.  Grow breast cells in culture and measure drug transport.  Develop models to help predict which drugs accumulate in breast milk.

18. Liver Systemic Circulation Tissues Kidney Metabolism DistributionAbsorption Excretion GI Pharmacokinetics

19. Liver is the site of drug metabolism P450

20.  Patients in a coma after heart attack now are having their body temperature lowered as a therapy, also being tested for spinal cord injury and trauma. Hypothermia and pharmacokinetics

21. Impact of interventions - hypothermia Hypothermic circulatory arrest, NIH Clinical Center, 1955

22. Impact of interventions - hypothermia

23. Relevance for pharmacotherapy

24. Animal experiments  Test the effects of hypothermia on drug metabolism when given after heart attack

25. Concentration-time curves

26. Children with brain injuries  Measure drug concentrations in the brain and the blood to see cold temperature effect.