Pharmacokinetics

1
Pharmacokinetics

• Chapters 8 and 11

2
Pharmacokinetics

• How is the drug absorbed, metabolized,
  distributed, and eliminated in the body
• Stability
• Chemical
• Metabolic
• Cytochrome P450s
• Drug-drug interactions

3
Pharmacokinetics

• Solubility
• Polarity
• Ionization
• Size

4
Pharmacokinetics

• Dosage
• Formulation of drug
• Methods of administration
• Oral
• Sublingual
• Rectal
• Epithelial
• Topical
• Nasal spray
• Eyedrops

• Inhalation
• Injection
• Intravenous
• Subcutaneous
• Intramuscular
• Intrathecal
• Implants

5
To control chemical and physical properties

• Drug design
• Alter functional groups
• Quantitative SARs
• Computational methods

6
Stability

• Option A Make drugs more resistant to metabolism
  and hydrolysis
• Steric shield
• Bioisosteres

7
Stability

• Stereoelectronic modifications
• Example lidocaine from novocaine

8
Stability

• Metabolic blockers
• Example
• Megestrol acetate

9
Stability

• Remove metabolic groups
• Example
• Chlorpropamide from tolbutamide

10
Stability

• Group Shifts
• Example
• Albuterol from noradrenaline

11
Stability

• Option B Make drugs less resistant to metabolism
• Toxicity
• Lingering side effects

12
Solubility

• Hydrophobic/hydrophilic balance
• Decrease polarity
• Increase polarity
• Ionization

13
Other factors in drug design

• Toxicity
• Prodrugs
• Valium ? nordazepam
• L-dopa ? dopamine
• Aspirin ? salicylic acid

14

• Sentry drugs
• Carbidopa
• Clavulanic acid and amoxicillin

15
Bioavailability

• Quantitative
• How much drug is available to reach the target,
  and at what rate?
• Takes into account
• Absorption
• Distribution
• Metabolism
• Excretion
• Differs with method of administration