BIOM 3090 Lecture Notes - Lecture 6: Intravenous Therapy, Enteric Coating, Paroxetine
9 Jun 2018
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Pharmacokinetics
- processes affecting the movement of drugs through the body (i.e. what the
body does to the drug)
- absorption, distribution, metabolism, excretion
- Absorption:
o Most drugs must first be absorbed into the systemic circulation from
their site of administration
▪ Required for most routes of drug administration except
intravenous route; intrathecal route, other minor routes
▪ Absorption first requires dissolution of drug (active pharm
ingredient) from its dosage form (formulation) before entering
circulation
▪ Rate of absorption affects: onset, duration and intensity of
action
o What affects rate of absorption from site of administration?
▪ Physiochemical drug (API) factors → lipid solubility, degree of
charge, size
▪ Physiological factors
• A large concentration gradient between site of drug
administration and surrounding tissue drives the
uptake of drug into the circulation
• Therefore, regional or local blood flow has the greatest
effect on maintaining a large concentration gradient
favouring drug absorption
▪ Drug formulation
• Refers to the physical form and chemical ingredients of
a medication
• Includes both the active drug (active pharm ingredient)
and any inactive chemicals (binders, excipients,
preservatives, etc) that comprise a pharm product
ready for administration to the patient by a specified
route of administration
• Modifications of the active pharm ingredient and/or
final formulation can be employed to
o Slow or delay the release of the API for
absorption
▪ More convenient as drug is less
frequently administered
▪ Usually for drugs with short elimination
half lives
▪ Modifications aimed at prolonging
dissolution phase of absorption
▪ dose-dumping or erratic absorption are
potential concerns
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▪ Enteric coated formulations of oral
medications protect them from
destruction by gastric juices; e.g.
Acetylsalicylic acid (aspirin)
• Enteric coated b/c delayed release
→ prevents API from being
exposed to the harmful digestive
enzyme before it gets to the
bowels
▪ Long lasting insulin’s; addition of proteins
(protamine, zinc or changes to
formulation pH to slow dissolution)
▪ Controlled release formulations or oral
medications; eg. Paroxetine
▪ Not all drugs are completely absorbed following
administration
• Bioavailability: fraction (%) of administered dose that
reaches the systemic circulation unchanged
▪ Bioavailability can be reduced/affected by:
• Precipitation of drug at injection site; unavailable for
absorption
• Unable to be absorbed by G.I. tract
o Physiochemical property of drug
o Reverse transport protein (P-glycoprotein)
• First pass” elimination effect following oral
administration of drugs
o primarily due to liver metabolizing enzymes
inactivating drug
o enzymes in G.I. tract wall can also metabolize
drug
o drug can also be excreted in bile
• Oral medications are presented to liver by portal
circulation before reaching systemic circulation
• GI tract → liver → heart → rest of body
• IV dose of a drug is 100% bioavailable (eg. 1200 mg
thiopental given IV)
• Nitroglycerin is metabolized (~90%) by liver following
oral administration
o Oral bioavailability: 10%
o Sublingual bioavailability: ~ 40% (can bypass
into stomach)
o ROUTES OF ADMINISTERATION
▪ Enteral: oral (per os; PO): most common method!
• Advantages: m
o most convenient for self-administration
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