Topic 6 Pharmacokinetics and Drug Metabolism · Drug candidate pharmaceutics are critical: ADME •Absorption •Distribution •Metabolism •Excretion. Drug candidate pharmaceutics
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Topic 6 Pharmacokinetics andDrug Metabolism
Chapter 8 Patrick
Drug candidate pharmaceutics are critical:ADME
• Absorption• Distribution• Metabolism• Excretion
Drug candidate pharmaceutics are critical:Drug Administration route-
1. Oral
2. Mucous membranes1. Rectal2. Oral (buccal)
3. Topical-transdermal4. Inhaled5. Injected
1. Intravenous2. Intramuscular3. Subcutaneous4. Intrathecal-spinal5. Intraperotoneal
Drug candidate pharmaceutics are critical:Formulations
1. Pills, capsules2. Liquid3. Patch4. Liposome/micelle
Pharmaceutics
TherapeuticWindow mustbe maintainedby dosing
TherapeuticWindow mustbe maintainedby dosing
Pharmaceutics
AbsorptionDrug Absorption, Metabolism and Excretionhttp://www.cc.nih.gov/training/training/principles/schedule.html
1. Acid-base properties
2. Hydrophobicity/Functional groups
3. Size
Drug molecule factors affecting absorption anddistribution
Lipinski’s rules for lousy drug absorption:1. MW>5002. H-bond donors>53. H-bond acceptors>104. log Partition coefficient > 5
i.e. octanol /water > 100,000:1
Absorption
A “good” drug
A “lousy” drug: insulin
Distribution:Serum Albumin, Thedistributor of non polar drugs
Seeing distribution: e.g.fluconazole
PET scan of 18F fluconazole
Metabolism/excretionOxidationPhase I Metabolism
Metabolism/excretion1. Phase 1 metabolism- Liver microsomal system
Metabolism/excretion1. Phase 1 metabolism- Liver microsomal system
Metabolism/excretion
Metabolism/excretion
Metabolism/excretion1. Phase 1 metabolism- Liver microsomal system
Metabolism/excretion1. Phase 1 metabolism
Metabolism/excretion1. Phase 1 metabolism
Metabolism/excretion
EXAMPLE: a Ca 2+ channel blocker for hypertension
EXAMPLE: a Ca 2+ channel blocker for hypertension
Phase II Metabolism
Metabolism/excretionConjugation examples
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