Related Experiment Videos
Effects of age on plasma protein binding of sufentanil
C Meistelman1, D Benhamou, J Barre
1Department of Anesthesiology, Institut Gustave-Roussy, France.
Insights
Sufentanil plasma protein binding is lower in newborns and infants due to decreased alpha-1-acid glycoprotein. This higher free fraction in neonates may enhance lipophilic opioid effects.
Area of Science:
- Pharmacology
- Biochemistry
Background:
- Sufentanil is a potent lipophilic opioid analgesic.
- Plasma protein binding influences drug distribution and efficacy.
- Age-related differences in protein binding are known for many drugs.
Purpose of the Study:
- To investigate the plasma protein binding of sufentanil across different age groups.
- To determine the relationship between sufentanil binding and plasma protein concentrations.
Main Methods:
- In vitro equilibrium dialysis was used to measure sufentanil free fraction.
- Radioactive tritiated sufentanil was employed for drug concentration determination.
- Plasma samples from newborns, infants, children, and adults were analyzed.
Main Results:
- The free fraction of sufentanil was significantly higher in newborns (19.5%) and infants (11.5%) compared to children (8.1%) and adults (7.8%).
- Sufentanil free fraction strongly correlated with alpha-1-acid glycoprotein (r = -0.73) and weakly with albumin (r = -0.35).
- Lower alpha-1-acid glycoprotein concentrations in neonates and infants likely explain reduced sufentanil protein binding.
Conclusions:
- Age-dependent variations in sufentanil plasma protein binding exist, primarily influenced by alpha-1-acid glycoprotein levels.
- The increased free fraction of sufentanil in neonates may contribute to enhanced clinical effects of lipophilic opioids.
Abstract:
The plasma protein binding of sufentanil has been studied in newborns, infants (0.5 +/- 0.3 yr), children (6.8 +/- 3.0 yr), and adults (39.5 +/- 9.0 yr). Binding of sufentanil was determined in vitro by equilibrium dialysis, and radioactive tritiated sufentanil was used for the determination of drug concentrations in plasma and buffer. The free fraction of sufentanil was significantly higher in the newborn (19.5 +/- 2.7%; P less than 0.01) than in the other age groups. The free fraction was also significantly higher in infants (11.5 +/- 3.2%; P less than 0.01) than in children (8.1 +/- 1.4%) or in adults (7.8 +/- 1.5%) but did not differ significantly between children and adults. The free fraction of sufentanil was strongly correlated with the alpha 1-acid glycoprotein plasma concentration (r = -0.73; P less than 0.001) whereas it was weakly correlated with albumin plasma concentration (r = -0.35; P less than 0.05). These data suggest that the lower concentration of alpha 1-acid glycoprotein in newborns and infants probably accounts for the decrease in protein binding of sufentanil in these age groups when compared with that in older children or adults. The increased free fraction in the neonate might contribute to the enhanced effects of lipophilic opioids in the neonate.