Pharmacy 303: Essentials of PHARMACOKINETICS Lecture PDF

Pharmacy 303: Essentials of PHARMACOKINETICS Dion R. Brocks, Ph.D. Medicinal chemists synthesizes a potential new drug Sends it to a world class pharmacologist for testing  A series of new drugs was developed to raise HDL cholesterol by inhibiting an enzyme involved in cholester...

Pharmacy 303: Essentials of PHARMACOKINETICS Dion R. Brocks, Ph.D. Medicinal chemists synthesizes a potential new drug Sends it to a world class pharmacologist for testing  A series of new drugs was developed to raise HDL cholesterol by inhibiting an enzyme involved in cholesterol production Enzyme inhibition experiment In vitro test results Indice Drug 1 Drug 2 Drug 3 IC50 nM 0.01 0.05 1 Emax (%) 100 100 100 Inhibition of enzyme activity is related to intended effect  Indice Drug 1 Drug 2 Drug 3 IC50 nM 0.01 0.05 1 Emax (%) 100 100 100 If given to humans which is expected to be most potent? A.Drug 1 B.Drug 2 C.Drug 3 Efficacy vs. Potency Emax IC50 Efficacy vs. Potency After administration to people In vitro Drug 1 Drug 2 Drug 3 IC50 nM 0.01 0.05 1 iv iv Oral Human iv dose dose dose dose Relative measure ‐ + +++ ++++ of effect WHY? In vitro can differ from in vivo  Pharmacology Meaning of the word Pharmac drugs ‐ ology the study of The study of drugs Pharmacodynamics: the study of the physiological effects of drugs at different concentrations Pharmacokinetics: the study of drug disposition (movement of drug in the body  Pharmacodynamics: What the drug does to the body Pharmacokinetics: What the body does to the drug  Pharmacodynamics: What the drug does to the body Pharmacokinetics: What the body does to the drug These two factors together dictate drug response in the whole body system  Administered Drug in Drug bloodstream PK Drug at Site of Action Drug + Receptor PD Physiological change  PVC's/hour (% of control) -5.5 0 20 40 60 80 100 120 -4 0.5 140 -3 0.5 -2 0.5 -1 0.5 -0 0.5 0 0. 50 1. 50 Time (h) 2. 50 3. 50 4. 50 5. 50 0 1 0.2 0.4 0.6 0.8 1.2 1.4 Serum mexiletine (mg/L) Concentration vs. effect relationships  Administered Drug in Drug bloodstream PK Drug at Site of Action Drug + Receptor Amiodarone Pharmacodynamic Response PD