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

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.

Drug concentration in blood Time

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

Drug Absorption

Drug Absorption

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

Absorption Transport Proteins

Liver Systemic Circulation Tissues Kidney Metabolism DistributionAbsorption Excretion GI Pharmacokinetics

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

Breast Physiology Modified from Breastfeeding (1994) by RA Lawrence

[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

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

Information for prescription drugs? All Marketed Drugs n = 1625

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.

Liver Systemic Circulation Tissues Kidney Metabolism DistributionAbsorption Excretion GI Pharmacokinetics

Liver is the site of drug metabolism P450

 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

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

Impact of interventions - hypothermia

Relevance for pharmacotherapy

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

Concentration-time curves

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