Clinical Pharmacology · MU Sofia

4. Clinical pharmacokinetics: application of the parameter "steady state plasma concentrations" of drugs in clinical practice.

Explains steady-state plasma concentration (Css) as drugs accumulate under repeated dosing, and what sets its height (dose rate and clearance) versus the time needed to reach it (half-life). Covers peak and trough swings with intermittent dosing, a table separating maintenance doses (clearance-based) from loading doses (volume-based), and clinical uses such as timing effect judgement, therapeutic drug monitoring, dose changes in renal or hepatic failure, drug interactions and adherence.

Inside: 4 sections · 1 table · 1 formula · 15 flashcards · 2 min

Topic 4 of 30 in the MU Sofia syllabus for Clinical Pharmacology (Medicine, Year 5). The free AceMed note covers it in 4 sections, about 288 words (2 min of reading), with 15 flashcards.

In this note

  1. Introduction
  2. What determines Css
  3. Maintenance and loading doses
  4. Clinical applications

Introduction

With repeated dosing a drug accumulates until the amount given equals the amount eliminated in each dosing interval. The concentration then fluctuates around a plateau: the steady-state concentration (Css).

What determines Css

where F is bioavailability, CL clearance and τ the dosing interval (for an infusion, Css = infusion rate ÷ CL).

  • Css depends on the dose rate and clearance: doubling the dose doubles Css (in linear kinetics); halving clearance doubles Css.
  • The time to reach Css depends only on the half-life: about 4–5 t½, whatever the dose. A higher dose reaches a higher plateau, not a faster one.
  • With intermittent dosing there is a peak (Css max) and a trough (Css min); the swing is smaller with shorter intervals, infusions or modified-release forms.

Maintenance and loading doses

A loading dose reaches the target at once when the half-life is long and the effect is needed quickly (e.g. digoxin, amiodarone, phenytoin, aminoglycosides, vancomycin).

Clinical applications

  1. When to judge effect: the full effect of a regular dose is seen only at steady state; do not increase the dose before 4–5 half-lives (unless a loading dose was given).
  2. When to measure levels (TDM): only at steady state, at the right time point (trough before the next dose; peak when toxicity is suspected).
  3. Dose changes: after any change, a new steady state is reached after another 4–5 half-lives.
  4. Kidney or liver failure: lower clearance → higher Css and a longer time to reach it; reduce the maintenance dose or lengthen the interval, keep the loading dose.
  5. Interactions: enzyme inhibitors raise Css, inducers lower it, over the following days.
  6. Compliance: missed doses lower Css; a low trough level suggests non-adherence.

Dose rate and clearance set the height of the steady state; half-life alone sets how long it takes to get there.

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