Related Experiment Video

Updated: Jun 26, 2026

An Intestine/Liver Microphysiological System for Drug Pharmacokinetic and Toxicological Assessment
08:59

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

Published on: December 3, 2020

Pharmacokinetic allometric scaling of antibodies: application to the first-in-human dose estimation

Iftekhar Mahmood1

  • 1Office of Blood Review & Research, Center for Biologic Evaluation and Research, Food & Drug Administration, Maryland, USA. iftekhar.mahmood@fda.hhs.gov

Journal of Pharmaceutical Sciences
|January 30, 2009
PubMed

The objectives of this study are: (i) to evaluate the predictive performance of interspecies scaling for antibodies to predict clearance, volume of distribution at steady state, and half-life in humans from animal data and (ii) to estimate first-in-human dose based on the predicted human clearance. Four methods were used to predict clearance in humans: (1) clearance versus body weight (simple allometry), (2) the product of clearance and maximum life-span potential (MLP) versus body weight, (3) the product of clearance and brain weight versus body weight, and (4) the application of a fixed exponent of 0.75. Based on the predicted human clearance, six methods were used to estimate the first-in-human dose. The predicted pharmacokinetic parameters and the estimated first-in-human dose of antibodies were compared with the observed human values. The results of the study indicated that the clearance of antibodies can be predicted with reasonable accuracy in humans and a good estimate of first human dose can be obtained from the predicted human clearance.

More Related Videos

An Open-Source Framework for Mass Calculation of Antibody-Based Therapeutic Molecules04:24

An Open-Source Framework for Mass Calculation of Antibody-Based Therapeutic Molecules

Published on: June 16, 2023

Stepwise Dosing Protocol for Increased Throughput in Label-Free Impedance-Based GPCR Assays06:13

Stepwise Dosing Protocol for Increased Throughput in Label-Free Impedance-Based GPCR Assays

Published on: February 21, 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...
Pharmacokinetic–Pharmacodynamic Relationship: Dose to Pharmacological Effect01:28

Pharmacokinetic–Pharmacodynamic Relationship: Dose to Pharmacological Effect

A drug’s dosage and pharmacokinetic properties determine how quickly it acts, how intense its effects are, and how long it lasts. Higher doses increase drug concentration at receptor sites, producing a hyperbolic curve when pharmacologic response is plotted against drug dose. Converting this scale to a log-linear format results in a sigmoidal curve, better representing dose–response relationships.For drugs following a one-compartment model, the pharmacologic response is directly proportional to...
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...
Physiological Pharmacokinetic Models: Assumption with Protein Binding01:13

Physiological Pharmacokinetic Models: Assumption with Protein Binding

Physiological models with protein binding in pharmacokinetics offer a sophisticated approach to understanding drug disposition. These models consider drug-protein interactions, enabling them to effectively predict drug concentrations in different organs and tissues. This precision aids in accurate drug dosing, providing a significant advantage over conventional models. A key process within these models is equilibration, which ensures that drug concentrations achieve a steady state within the...
Pharmacokinetic Models: Comparison and Selection Criterion01:26

Pharmacokinetic Models: Comparison and Selection Criterion

Physiological and compartmental models are valuable tools used in studying biological systems. These models rely on differential equations to maintain mass balance within the system, ensuring an accurate representation of the dynamic processes at play.
Physiological models take a detailed approach by considering specific molecular processes. They can predict drug distribution, metabolism, and elimination changes, providing a comprehensive understanding of how drugs interact with the body.