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Pharmacokinetics & Drug Transport

Delve into the intricate processes of drug transport in pharmacokinetics and its impact on therapy. Understand how absorption, distribution, metabolism, and excretion influence drug concentration and effectiveness.

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Pharmacokinetics & Drug Transport

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  1. 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. TOXIC Drug concentration in blood No Effect Time

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

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

  6. Drug Absorption

  7. Absorption Transport Processes H+ H+ H+ H+ Lumen H+ H+ H+ H+ H+ ATP ATP Passive Facilitated Active Active Blood

  8. Absorption Transport Proteins

  9. Pharmacokinetics GI Liver Systemic Circulation Tissues Distribution Absorption Metabolism Excretion Kidney

  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. Transporters in breast barrier cells Transporters upregulatedduring lactation Transporters upregulatedduring lactation 10* 7 Transporters expressed in LMECs at a level similar or greater than othersecretory tissues  [PE1]Need to fix axis

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

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

  15. 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.

  16. Pharmacokinetics GI Liver Systemic Circulation Tissues Distribution Absorption Metabolism Excretion Kidney

  17. Liver is the site of drug metabolism P450

  18. Hypothermia and pharmacokinetics • 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.

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

  20. Impact of interventions - hypothermia

  21. Relevance for pharmacotherapy

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

  23. Concentration-time curves

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

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