Related Experiment Video

Updated: Jun 24, 2026

Comprehensive Evaluation of the Effectiveness and Safety of Placenta-Targeted Drug Delivery Using Three Complementary Methods
09:04

Comprehensive Evaluation of the Effectiveness and Safety of Placenta-Targeted Drug Delivery Using Three Complementary Methods

Published on: September 10, 2018

Cefazolin plasma protein binding saturability during pregnancy

Karel Allegaert1, Tim Van Mieghem, Rene Verbesselt

  • 1Neonatal Intensive Care Unit, Division of Woman and Child, University Hospitals Leuven, Leuven, Belgium. karel.allegaert@uz.kuleuven.ac.be

Methods and Findings in Experimental and Clinical Pharmacology
|April 10, 2009
PubMed

This article aims to document cefazolin (CFZ) plasma binding and its covariates during pregnancy and compare these observations with previously reported observations in nonpregnant adults. Maternal CFZ plasma samples were collected during in utero surgery. The unbound CFZ fraction was reported by median and range. Correlation (Spearman) and multiple regression were used to identify covariates (total CFZ concentration, albuminemia, gestational age) of the unbound CFZ fraction. Observations during pregnancy were compared with observations in nonpregnant adults (unpaired t test, multiple regression). Plasma (N = 130) samples were collected during 30 interventions. The median unbound CFZ fraction was 0.25 (range 0.14-0.41). Correlations between the unbound CFZ fraction and total CFZ plasma concentration (0.46), time after administration (-0.38), albuminemia (-0.39) and gestational age (-0.19) were statistically significant. The median unbound CFZ fraction was higher during pregnancy when compared to observations in nonpregnant adults (0.25 vs. 0.19, P < 0.001). In a multiple-regression model, total plasma CFZ concentration and albuminemia were covariates of the unbound CFZ fraction (r(2) = 0.4). The concept of saturability of CFZ plasma protein binding has been confirmed during pregnancy, but the free CFZ fraction is higher, likely explained by the lower albuminemia during pregnancy.

Related Concept Videos

Drug Distribution: Plasma Protein Binding01:29

Drug Distribution: Plasma Protein Binding

Drugs predominantly attach to plasma proteins, with only a small percentage remaining unbound. The unbound portion can be calculated as one minus the bound fraction. Acidic drugs form large, inactive complexes by reversibly binding to plasma albumin, which prevents them from diffusing across biological barriers. These drug-protein complexes act as reservoirs for the drugs. As the concentration of unbound drugs decreases, these complexes quickly dissociate to release the free drug, maintaining...
Factors Affecting Protein-Drug Binding: Protein-Related Factors01:20

Factors Affecting Protein-Drug Binding: Protein-Related Factors

Drug binding to proteins is a key aspect of pharmacokinetics and can influence a drug's distribution, absorption, and elimination in the body. Several factors, including the drug's physiochemical properties, protein concentration, disease states, and the number of binding sites on the protein, influence this process.
The physicochemical properties of a drug play a significant role in its ability to bind to proteins. Lipophilic drugs, which dissolve in fats, oils, and lipids, can be bound by...
Factors Affecting Protein-Drug Binding: Patient-Related Factors01:29

Factors Affecting Protein-Drug Binding: Patient-Related Factors

Protein-drug binding, a pivotal aspect of pharmacokinetics, is subject to considerable variability influenced by an array of patient-related factors. The intricate interplay of age, individual differences, and pathological conditions significantly impact the binding dynamics and subsequent pharmacological effects.
Age stands as a key determinant in protein-drug binding. Neonates, characterized by low albumin content, experience heightened concentrations of unbound drugs such as phenytoin and...
Factors Affecting Protein-Drug Binding: Drug-Related Factors01:18

Factors Affecting Protein-Drug Binding: Drug-Related Factors

Drug binding to proteins is a complex phenomenon influenced by various drug-related factors, each playing a significant role in the interaction between drugs and proteins within the body.
One crucial factor in drug-protein binding is the drug's lipophilicity or its affinity for fat. More lipophilic drugs tend to have higher binding extents. For example, highly lipophilic drugs like cloxacillin exhibit substantial protein binding, with as much as 95% of the drug binding to proteins. In contrast,...
Hepatic Drug Clearance: Effect of Protein Binding01:09

Hepatic Drug Clearance: Effect of Protein Binding

Hepatic clearance is influenced by protein binding based on the drug's extraction ratio. Drugs with high extraction ratios are considered flow-limited and remain unaffected by protein binding during hepatic clearance. On the other hand, drugs with low extraction ratios may be impacted by plasma protein binding, although the extent of this influence depends on the fraction of the drug bound.
For low-extraction-ratio drugs that are less than 80% protein-bound, minor changes in protein binding...
Factors Affecting Protein-Drug Binding: Drug Interactions01:23

Factors Affecting Protein-Drug Binding: Drug Interactions

Drug interactions are a critical aspect of pharmacology and can occur when two or more drugs compete for the same binding site. This competition can result in one drug displacing another, altering the effect of the displaced drug. Drug interactions are complex processes that rely heavily on how much of the displacer drug is present and how strongly it can bind to the same sites as the displaced drug.
Displacement interactions can have varying outcomes, ranging from toxicity to virtually...