Pharmacokinetics: the study of how medications enter the body, reach the site of action,
metabolize and exit the body.
1. An elderly male admitted with CAP. He’s getting levofloxacin 500 mg IV once daily and
is switched to 500 mg po after he has improved clinically. Why is the oral and IV dose the
Answer: There is no first pass. Bioavailability is the same (PO/IV= 100)
2. A 56 year old male with angina receiving sublingual nitroglycerin.Why do we give nitro
Answer: bi pass first pass effect
3.A 42 year old female with nephrolithiasis who received morphine 2.5 mg IV q4h and is
discharged from the ER with a prescription for 10 mg po q4h of morphine IR. Why is the
po dose of oral morphine higher than the IV?
Answer: It has a lower bioavailability via mouth
4. A 72 year old male admitted with rhabdomyolysis. The physician reviews his usual
medications and writes an order to “hold simvastatin & erythromycin”.Why did the
physician specifically hold these two drugs? 1. Absorption:
- Movement of a drug from its site of administration to the blood
- the fraction of unchanged drug reaching the systemic circulation after administration by any route
- Rate (time to onset) and extent/amount (intensity of effect) are different for various routes of
administration. *** Barriers to absorption with each route are different.
1. Rate of dissolution: tablets could yield more rapid onset
- ability to dissolve depends on its form or preparation. Solutions/suspensions are in a
liquid state and are absporbed more readily.
- Acidic meds pass through GI mucosa rapidly.
- Meds with a basic pH do not get absorbed before reaching the small intestine
2. Surface area: Larger surface area, more likely to be absorbed (intestine)
3. Blood flow: More absorption when blood flow is high (creates a conc. Gradient) (e.g.
with insulin- don’t massage the injection site)
4. Lipid solubility: More lipid soluble more readily absorbed (charge v uncharged, lipid
- Highly lipid soluble medications easily cross the cell membrane and are absorbed
- Absorption of medication is impacted by food in the stomach.
5. pH partitioning: ASA Ion Trapping: ASA is nonionized in the stomach; therefore it
is absorbed in the stomach. However, it becomes ionized in the intestines, which is
why it is not absorbed. Ions cannot cross the membrane. Drugs will accumulate on the
side that pH favors ionization.
6. Route of administration: Each route has a different rate of absorption
- ie. When applied to the skin/oral, absorption is slower. Mucous membranes and
respiratory airways are quicker because the these tissues are highly vascular. IV is the
Polar + ions cannot cross the cytoplasmic membrane. Lipid Soluble can!
Bioavailability (F value) : the ability of a drug to be released from its dosage form and to be
dissolved, absorbed, and transported by the body to the drug’s site of action.
- For an IV drug, F generally 1= 100%
- IV formulation: No barriers to absorption (virtually all drug in blood instantaneously)
- For oral drugs – bioavailability is often less than 100% due to incomplete absorption at the site
- 100% means that it all reaches circulation/unchanged, 0% means none of it does Examples (oral): Barriers to oral bioavailability
1. Inactivation or destruction in stomach (e.g insulin)
2. binding interactions with drugs (iron and dairy)
3. metabolism in lining of gut, first pass effect (ETOH)
4. malabsorptive syndromes
5. pH, gastric emptying, GI mobility, vomiting, etc.
AUC: Area under the curve (total exposure of the body to a drug)
Cmax: maximal concentration achieved with dosage form (peak)
Tmax: time at which it happens
- Movement of drugs throughout the body.
- Affected by protein binding (e.g. Phenytoin (Dilantin) free drug is active (able to exert
1. Blood flow to tissues- Problem conditions – abscesses, tumours do not have a blood
supply, which can effect drug therapy.
2. Exiting the vascular system– Since drug do not produce their effects in the blood-
they need to leave the vascular system. The drugs leave through capilliary beds (between
the cells), which is vital for metabolism and excretion.
- BBB – allows only fat soluble medications to pass into the brain and cerebral
spinal fluid. Due to tight junctions in capillary beds drugs – pass through cells of
the capillary wall. They need lipid solubility or transport pump - protein binding - bound and free drug. Albumin has no way to leave the
3. Entering cells- Enter cells for metabolism and excretion & for some, in order to have
- Most meds bind to a protein to some extent.
- Meds bound to albumin cant have activity. Only unbound meds are active.
- Older adults have a decrease in albumin, which is a result of a change in liver fx. This
is why they are more at risk f