Related Experiment Video

Updated: Jul 3, 2026

Use of Rabbit Eyes in Pharmacokinetic Studies of Intraocular Drugs
10:02

Use of Rabbit Eyes in Pharmacokinetic Studies of Intraocular Drugs

Published on: July 23, 2016

Methods to account for inaccuracies in the dosing history when performing population pharmacokinetic analysis

Venkata V Pavan Kumar1, Stephen B Duffull

  • 1School of Pharmacy, University of Otago, Dunedin, New Zealand. pavan.kumar@otago.ac.nz

Pharmaceutical Research
|July 9, 2008
PubMed
Abstract

Insights

A new method, the concentration time method (CTM), effectively addresses missing dose history in pharmacokinetic modeling. CTM provides accurate parameter estimates comparable to ideal methods when nominal dosing information is available.

Area of Science:

  • Pharmacokinetics
  • Pharmacometric modeling
  • Drug development

Background:

  • Accurate dose history is crucial for pharmacokinetic (PK) modeling.
  • Missing dose history (MDH) is a common challenge in PK analysis.
  • Existing methods for handling MDH have limitations.

Purpose of the Study:

  • To develop and evaluate novel methods for accounting for missing dose history.
  • To assess the performance of different approaches in handling MDH in PK studies.

Main Methods:

  • A simulation study was conducted using NONMEM with varying doses, timings, and formulations.
  • Four methods were compared: ideal dose method (IDM), concentration minimum method (CMM), extrapolation subtraction method (ESM), and the novel concentration time method (CTM).
  • CTM estimates the time of the previous dose event to account for MDH.

Main Results:

  • The concentration time method (CTM) demonstrated superiority over the extrapolation subtraction method (ESM) and concentration minimum method (CMM).
  • Parameter estimates obtained using CTM were comparable in accuracy to those from the ideal dose method (IDM).

Conclusions:

  • The concentration time method (CTM) is a simple and effective approach for managing potential inaccuracies in dose history.
  • CTM is particularly useful when nominal dosing history is available, improving PK model reliability.

More Related Videos

Comprehensive Analysis of Drug Response using the FLICK Assay09:42

Comprehensive Analysis of Drug Response using the FLICK Assay

Published on: June 6, 2025

An Intestine/Liver Microphysiological System for Drug Pharmacokinetic and Toxicological Assessment08:59

An Intestine/Liver Microphysiological System for Drug Pharmacokinetic and Toxicological Assessment

Published on: December 3, 2020

Related Concept Videos

Dosage Regimens: Partial Pharmacokinetic Parameters01:01

Dosage Regimens: Partial Pharmacokinetic Parameters

It is not uncommon for complete drug pharmacokinetic profiles to remain elusive in pharmacokinetics. This necessitates certain educated assumptions by pharmacokineticists to determine appropriate dosage regimens without comprehensive pharmacokinetic data from animal or human studies. One prevalent assumption is setting the bioavailability factor, denoted as F, to 1 or 100%. This assumption caters to the scenario where a drug doesn't achieve full systemic absorption, resulting in the patient...
Analysis of Population Pharmacokinetic Data01:12

Analysis of Population Pharmacokinetic Data

Analysis of population pharmacokinetic data involves studying the behavior of drugs within diverse populations to understand their pharmacokinetic parameters. Traditional pharmacokinetic methods typically involve collecting samples from a few individuals and estimating these parameters. While these methods are commonly used, they have limitations in capturing the variability in drug response among individuals or heterogeneous populations. Population pharmacokinetics is employed to address these...
Dosage Regimens: Designs and Approaches01:28

Dosage Regimens: Designs and Approaches

Designing a dosage regimen, which refers to the manner of drug administration, is a complex process involving the selection of drug dose, route, and frequency. This process is underpinned by pharmacokinetic parameters derived from tests and population averages. These parameters are then tailored to patient-specific variables such as diagnosis, demographics, and allergy status. Once therapy commences, therapeutic response monitoring is critical and achieved through clinical and physical...
Drug Accumulation During Multiple Dosing: Repetitive IV Injections01:21

Drug Accumulation During Multiple Dosing: Repetitive IV Injections

Calculating drug dosage and accumulation in multiple-dose regimens is crucial for achieving therapeutic efficacy while avoiding toxicity. This involves determining the plasma drug concentrations over time to optimize dosing schedules. The principle of superposition is fundamental in this process, allowing for the prediction of drug concentration in plasma following multiple doses based on single-dose data.The principle of superposition asserts that the plasma concentration-time curves from...
Pharmacokinetic–Pharmacodynamic Relationship: Problems01:24

Pharmacokinetic–Pharmacodynamic Relationship: Problems

The empirical approach to drug therapy optimization relies on correlating pharmacological response with administered dosage. Such an approach can be costly, time-consuming, and often yields poor correlation due to variables like formulation factors and drug elimination characteristics. A more precise approach correlates response with plasma drug concentration or the amount of drug in the body, rather than dosage. This is achieved through pharmacokinetic-pharmacodynamic (PK/PD) modeling, which...
Drug Dosing in Renal Diseases: Dose Adjustments Based on Drug Clearance and Elimination Rate Constant01:25

Drug Dosing in Renal Diseases: Dose Adjustments Based on Drug Clearance and Elimination Rate Constant

In patients with renal disease, dosage adjustments are necessary to maintain therapeutic plasma drug concentrations and prevent toxicity or subtherapeutic exposure. Renal impairment alters drug pharmacokinetics, especially in conditions like uremia, where changes such as prolonged elimination half-life and altered apparent volume of distribution can significantly affect drug disposition. These changes require careful modification of the dosing regimen to achieve the desired clinical...