Neonates plasma protein binding

L. Notarianni, Plasma protein binding of drugs in pregnancy and in neonates, Clin. Pharmacokinet, 18, 20 (1990). 

Absorption/Distrlbutlon - Phenytoin is slowly absorbed from the small intestine. Rate and extent of absorption varies and is dependent on the product formulation. Bioavailability may differ among products of different manufacturers. Administration IM results in precipitation of phenytoin at the injection site, resulting in slow and erratic absorption, which may continue for up to 5 days or more. Plasma protein binding is 87% to 93% and is lower in uremic patients and neonates. Volume of distribution averages 0.6 L/kg. Phenytoin s therapeutic plasma concentration is 10 to 20 mcg/mL, although many patients achieve complete seizure control at lower serum concentrations. 

The plasma protein binding of drugs bound to albumin and AAG in neonates is significantly lower than that... 

The toxic concentrations for theophylline in neonates have not been well defined, and can vary from infant to infant. Other pharmacokinetic factors, such as low plasma protein binding and limited capacity for excretion could make neonates prone to aminophylline toxicity. Fetuses and neonates can develop theophylline toxicity even with plasma concentrations in the target range, since they can metabolize theophylline to caffeine, adding to the methyl-xanthine load. 

Competition between drugs for plasma protein-binding sites may increase the free fraction, possibly enhancing the effects of the drug displaced. Example sulfonamides and bilirubin in a neonate... 

Drug interactions Competition with warfarin and methotrexate for plasma protein binding transiently increases the plasma levels of these drugs. Sulfonamides can displace bilirubin from plasma proteins, with the risk of kemicterus in the neonate if used in the third trimester of pregnancy. 

Plasma protein binding is altered in neonates and young infants due to changes in the amount and composition of circulating plasma... 

Once absorbed, foreign compounds may react with plasma proteins and distribute into various body compartments. In both neonates and elderly human subjects, both total plasma-protein and plasma-albumin levels are decreased. In the neonate, the plasma proteins may also show certain differences, which decrease the binding of foreign compounds, as will the reduced level of protein. For example, the drug lidocaine is only 20% bound to plasma proteins in the newborn compared with 70% in adult humans. The reduced plasma pH seen in neonates will also affect protein binding of some compounds as well as the distribution and excretion. Distribution of compounds into particular compartments may vary with age, resulting in differences in toxicity. For example, morphine is between 3 and 10 times more toxic to newborn rats than adults because of increased permeability of the brain in the newborn. Similarly, this difference in the blood-brain barrier underlies the increased neurotoxicity of lead in newborn rats. 

Indomethacin is absorbed after oral administration reaching peak plasma concentrations after 2 h. About 99% binds to plasma proteins and it has a variable terminal half-life from 2.6 to 11.2 h in adults and up to 30 h in neonates. The metabolites generated in the liver are desmethyl-indomethacin, desbenzoyl-indomethacin,... 

Protein Binding. In plasma, about 40% (temperature and pH-dependent) decreased in neonates and in subjects with hepatic cirrhosis. 

Less extensive binding of drugs to plasma proteins is generally without clinical importance but there is a significant risk of elevation of plasma bilirubin (in the neonate) following its displacement from protein binding sites by vitamin K, x-ray contrast media or indomethacin. 

Severe poisoning in a hypoalbuminemic neonate responded unusually to peritoneal dialysis, possibly because of reduced phenytoin binding to plasma proteins (SEDA-16, 73). 

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