Volume of distribution = dose/plasma concentration at time of administration
With repeated administration, the plasma concentration is a function of the rate of administration and the rate of elimination

Achieves steady state within 3-4 half-lives
Steady state can be achieved faster by using a loading dose
Drug half-life determines the frequency of subsequent doses

Bioavailability: the amount of oral dose that reaches the systemic circulation and is available to the site of action

May be limited by first-pass metabolism

Gut motility
Intestinal pH, bile salts
Enterohepatic circulation
Intestinal blood flow
Intestinal microflora

Ocular topical drugs have higher bioavailability as they are absorbed via nasal mucosa and so avoid first-pass metabolism

Drug kinetics

First-order: linear increase in rate with increased drug concentration
Zero-order: saturation at high drug concentrations

Eg. when the capacity of liver enzymes is consumed

Drug penetration of cells

Diffusing through lipid (depends on lipid solubility)
Diffusion through aqueous pores
Via carrier molecules
Pinocytosis

Drug distribution

Binding affinity for plasma proteins eg. albumin

Highly bound drugs tend to remain in the plasma

Binding to tissue proteins
Blood flow to different tissues

The blood-retinal and blood-aqueous barriers limit drug distribution in the eye. Usually only lipid-soluble drugs move between the blood and the retina. Systemically administered drugs do not necessarily produce high intraocular levels

Drug metabolism

Occurs almost entirely in the liver
Increases drug solubility for excretion
Might activate a prodrug to its active form

May inactivate others

Phase I: oxidation

Performed by cytochrome p450
This group of enzymes also exists in the eye
Numerous inducers and inhibitors (including chloramphenicol)

Phase II: conjugation

Drug excretion

Renal excretion: varies widely between drugs depending on the kidneys capacity to handle the drug’s properties

Glomerular filtration (if not protein-bound and small enough ie. <20,000Da)
Tubular secretion into the glomerular filtrate
Reabsorption

Biliary excretion

Conjugated drugs are concentrated in the bile and delivered to the intestine
Drug may be released and re-absorbed (enterohepatic circulation)