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Pharmacokinetics

Pharmacocinetica

For medical students2 min readUpdated 2026-10-10

Pharmacokinetics is the branch of pharmacology that studies the processes of drug absorption, distribution, and elimination. Key parameters include the rate of drug penetration into the systemic circulation, crossing the hepatic barrier, and the mathematical patterns of elimination.

BarrierThe liver performs presystemic elimination of substances

OutflowThe rectum features a dual venous drainage system

Calculation0.693 is the natural logarithm of two used in the half-life formula

Absorption and the First-Pass Effect

One of the most critical concepts for understanding bioavailability is how the anatomical features of venous drainage affect a drug's fate. The key concept here is the first-pass effect through the liver.

When a drug is absorbed in the gastrointestinal tract, it does not always enter the general circulation directly. If venous blood from the organ collects in the portal vein (v. portae), the substance inevitably passes through the liver, where it undergoes metabolism (presystemic elimination). This significantly reduces the dose that ultimately reaches the target organs.

Anatomy of Rectal Administration

Drug administration via the rectum is characterized by a rapid rate of penetration into the systemic circulation due to the unique vascular architecture of this region. Absorption is distributed between two venous drainage beds:

Lower and middle rectum: Approximately half of the administered dose is absorbed here. Blood drains into the middle and inferior rectal veins (vv. rectales mediae et inferiores), which empty directly into the inferior vena cava (v. cava inferior). Thus, the drug enters the systemic circulation, completely bypassing the liver and avoiding the first-pass effect.
Upper rectum: The remainder of the dose is absorbed here. Outflow occurs via the superior rectal vein (v. rectalis superior), which carries blood into the portal vein (v. portae). This portion of the drug is delivered to the liver and undergoes presystemic elimination.

Elimination Kinetics

Mathematical models are used to describe drug elimination processes. First-order kinetics is the most common model encountered in medical practice.

The principal relationship in this model is the dependency between a drug's half-life and its elimination rate constant. It is expressed by a strict formula where the half-life equals the natural logarithm of 2 divided by the rate constant. Numerically, the natural logarithm of 2 is rounded to 0.693.

Mnemonic

To remember rectal venous drainage: "Lowers go to systemic, uppers go to hepatic" (inferior veins drain into the inferior vena cava, superior vein drains into the portal vein).

Frequently asked questions

Which routes of drug administration avoid the first-pass effect?

Sublingual administration and administration into the lower and middle parts of the rectum avoid the first-pass effect.

Sublingual (sublingualis) — absorption directly into the systemic circulation, bypassing the liver.
Lower and middle rectum — absorption occurs into the middle and inferior rectal veins (vv. rectales mediae et inferiores), bypassing the liver.

What are the types of elimination kinetics?

To describe the decline in drug concentration, the following kinetic types are distinguished:

First-order kinetics — exponential, with a variable rate.
Zero-order kinetics — linear, with a constant rate (saturable kinetics).

Which pharmacokinetic parameters describe drug distribution?

The distribution of drugs in the body is described by the apparent volume of distribution.

Apparent volume of distribution (apparent volume of distribution, $V_d$) — the theoretical volume of fluid that would be required to contain the total amount of drug in the body at the same concentration as in the blood plasma.

Which organs participate in presystemic drug elimination?

The following organs participate in presystemic drug elimination:

Liver — the primary site of presystemic metabolism and drug breakdown.
Intestinal wall — an extrahepatic site of metabolism, second only to the liver in activity.
Kidneys — sites of extrahepatic metabolism.

How does first-order kinetics differ from zero-order kinetics?

The differences between elimination kinetics types lie in the pattern of rate change and concentration dependence:

Parameter	First-Order Kinetics	Zero-Order Kinetics
Rate Character	Variable rate, exponential	Constant rate, linear
Dose Dependency	$t_{1/2}$ is constant, dose-independent	Depends on enzyme saturation
Graph	Exponential curve	Straight line

What parameters are necessary to calculate total drug clearance?

Pharmacokinetic parameters and measures of administration or elimination rates are used to calculate total drug clearance:

Elimination rate — amount of substance eliminated per unit time.
Concentration — drug concentration in a biological fluid ($C$).
Apparent volume of distribution ($V_d$) and elimination rate constant ($k_{el}$).
Steady-state concentration ($C_{ss}$) and infusion rate during continuous infusion.

What is the first-pass effect?

It is the process of presystemic elimination (metabolism) of a drug in the liver, reached via the portal venous system immediately after absorption, before the drug enters the general systemic circulation.

Why does a portion of a rectally administered drug evade hepatic metabolism?

Because about 50% of the dose is absorbed in the lower and middle thirds of the rectum, where blood drains into the inferior vena cava, bypassing the portal system and the hepatic barrier.

How are the half-life and elimination rate constant related in first-order kinetics?

They are inversely proportional. The half-life is calculated as 0.693 (the natural logarithm of two) divided by the elimination rate constant.

Go deeper

Mechanisms of hepatic presystemic elimination
Anatomy of rectal blood supply
Calculation of drug half-life
Differences between first-order and zero-order kinetics
Impact of the hepatic barrier on bioavailability