BIOM3401 Lecture Notes - Lecture 1: Intravaginal Administration, Subcutaneous Injection, Drug Metabolism
BIOM - Lecture : ADME Suary
ad Drug Forulatio
Pharmacokinetics Summary
• Defined as the measurement and formal
interpretation of changes with time of drug
concentrations in one or more different regions
of the body in relation to dosing
• Characterised by the kinetics of drug
absorption, distribution, metabolism and
elimination
Absorption = the passage of a drug from its site of administration into blood
• Defied the ter ioaailailit
o The proportion of a drug dose that
reaches the blood (systemic circulation)
• Calculated as
o AUC = area under the curve
• Routes of administration
o Intravenous
▪ 100% of drug enters
the systemic
circulation = 100%
bioavailability
o Oral
o Sublingual
o Percutaneous/transdermal
o Nasal sprays
o Inhalation
o Subcutaneous injection
o Intramuscular
o Rectal
o Intravaginal
o Ocular
• Factors affecting drug absorption
o Drug disintegration/solubility (drug formulation)
o Drug physicochemical interaction with solvent/local components
o Drug physicochemical properties (affect drug diffusion, membrane
permeability)
o Drug dose
o Permeability across membrane barrier(s)
o Gut contents, GIT motility & splanchnic blood flow (for oral delivery)
o First pass metabolism and metabolism (oral)/degradation at site of
administration
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o Local blood/lymphatic flow rate (e.g. for SC delivery, required to remove drug
from site)
Distribution = reversible transfer of a drug from one compartment of the body into
another
• Normally represented as a volume
o VC = iitial or etral olue of distriutio
▪ Calculated at the point at which the drug is administered
▪ For drugs that are cleared very slowly from the blood, VC
approximately equals the volume of plasma/serum
▪ For drugs that are cleared rapidly from the blood, VC is very large
o VDß = olue of distriutio durig the terial or eliiatio phase of the
plasma concentration-time profile
▪ Very high for drugs that extensively distribute into total body water
▪ Very low for drugs that only slowly escape from blood
• Biodistribution represents where a drug goes
• Example: after oral delivery -> drug is absorbed into the blood -> drug distributes out
of the blood into other aqueous compartments of the body (depending on the
affinity of the drug for cells, components in the compartment)
• Example: distriutio ad iodistriutio dooruii ad ael i rats after IV
administration at 2mg/kg
o Doxorubicin is a small molecule that rapidly distributes out of the blood and
into whole body water, but the much larger caelyx distributed slowly out of
the blood
o Doxorubicin biodistributes almost evenly into all organs and tissues of the
body, including tumour tissue, but caelyx biodistribution is mainly into the
liver/spleen and tumour
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Document Summary
Biom(cid:1007)(cid:1008)(cid:1004)(cid:1005) - lecture (cid:1005): adme su(cid:373)(cid:373)ary a(cid:374)d drug for(cid:373)ulatio(cid:374) Intravenous: 100% of drug enters the systemic circulation = 100% bioavailability, oral, sublingual, percutaneous/transdermal, nasal sprays. Inhalation: factors affecting drug absorption, subcutaneous injection. Low or variable oral bioavailability: poorly water-soluble drugs, poorly permeable drugs, biopharmaceutics classification system (bcs), classifies drugs based on, solubility, permeability. Rapid clearance or undesirable biodistribution profiles: small molecule drugs, major problem in cancer chemotherapy. Inherent solubility < 0. 03mg/ml: soluble in 1:1 chremophore el (castor oil): ethanol, side effects, hair loss, nausea/vomiting, muscle/joint pain, diarrhoea, tachycardia/chest pain, hypotension, rash, hypersensitivity reactions, *effects due to the chremophore, erythrocyte aggregation, neurotoxicity. Enhanced permeation from blood into tumour interstitium and retention within tumour interstitium. Vasculature in normal tissue are very well constructed. Very tight junctions and intact basement membrane. Nanomedicines are so large molecules inside the blood from escaping from the blood large the(cid:455) do(cid:374)(cid:859)t es(cid:272)ape out of the normal vasculature, though some do escape and gain access into the interstitium.
