Non-Compartmental Analysis

This interactive module demonstrates non-compartmental analysis (NCA) techniques for antimicrobial pharmacokinetic data analysis. Learn how to calculate key PK parameters directly from concentration-time data without assuming a specific compartmental model.

Patient Generator

  • Age: - years
  • Sex: -
  • Height: - cm
  • Weight: - kg
  • Creatinine: - mg/dL

Medium (Standard Oral)

PK Parameters

0.8

0.1

0.7 L/kg

0.8

Dosing

0 mg

250 mg

24 hrs

10 days

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20 mg/L

5 mg/L

Subject Drug Name Age Sex Ht (cm) Wt (kg) BMI IBW (kg) Adj IBW (kg) Creatinine (mg/dL) CrCl (mL/min) Loading Dose (mg) Dose (mg) Interval (hrs) Duration (days) Clearance (L/h) Volume (L) Fraction Unbound Vss,u (L) Bioavailability Half-life (h) Css,avg AUC0-24h Cmax AUC/Efficacy Cmax/Efficacy Time>Efficacy (%)

Non-Compartmental Analysis (NCA) Fundamentals

Model-Independent Approach: NCA calculates pharmacokinetic parameters directly from observed concentration-time data without assuming a specific compartmental model. This makes it ideal for regulatory submissions and clinical practice where model assumptions may not hold.

Key NCA Parameters: - AUC (Area Under the Curve): Total drug exposure calculated using the trapezoidal rule - Cmax: Maximum observed concentration - Tmax: Time to maximum concentration
- Clearance (CL/F): Dose/AUC for extravascular administration - Terminal Half-life: Calculated from the terminal elimination phase

Advantages of NCA: - No model assumptions required - Robust to sparse sampling - Regulatory gold standard - Less prone to bias than compartmental methods

Clinical Applications: NCA is particularly valuable for: - Bioequivalence studies - Dose proportionality assessments - First-in-human studies - Population PK analysis input data

Blood Sampling Strategy

In this simulation, blood samples are collected every 1 hour to provide a detailed view of how pharmacokinetic data is collected in clinical practice. This sampling frequency allows us to:

  • Capture both peak and trough concentrations
  • Observe the full absorption and elimination phases
  • Reduce the burden on patients compared to more frequent sampling
  • Provide sufficient data points for pharmacokinetic analysis

Simplified Pharmacokinetic Model

This simulation uses a simplified one-compartment model with first-order absorption that focuses on the minimum essential parameters needed to generate a multiple dosing pharmacokinetic plot:

Essential PK Parameters: - Clearance (CL): Automatically calculated from patient’s creatinine clearance using Cockcroft-Gault equation - Volume of Distribution (Vd): Drug-specific volume per kg multiplied by patient weight - Bioavailability (F): Fraction of dose reaching systemic circulation

Patient-Specific Factors: - Creatinine Clearance: Calculated using Cockcroft-Gault: CrCl = [(140 - age) × weight × (0.85 if female)] / (72 × serum creatinine) - Weight-Based Dosing: Volume of distribution scales directly with patient weight

Dosing Parameters: - Dose: Amount of drug administered per dose - Dosing Interval: Time between doses - Treatment Duration: Total length of treatment

This approach incorporates key patient-specific factors (age, sex, weight, creatinine) while maintaining the core functionality needed to understand multiple dosing pharmacokinetics and the clinical application of the Cockcroft-Gault equation.

Test your understanding by calculating the following parameters for the current patient:

1. Creatinine Clearance (mL/min):

2. Adjusted Body Weight (kg):

3. Volume of Distribution of Unbound Drug (L):

4. Time to Steady State - tss (hours):

5. Average Steady-State Concentration - Css,avg (mg/L):