Infants plasma protein binding

Distribution addresses the transfer of the drug compound from the site of administration to the systemic circulation and then to bodily tissues. Both in vitro and in vivo studies are informative here. In vitro studies, for example, examine plasma protein binding. In vivo studies use whole body autoradiography that can display visually how much drug has reached different parts of the body. Transfer of the drug compound in milk to an infant and across the placenta is also studied. 

To study the plasma protein binding at least in newborns and infants is recommended, as the protein binding is reduced in the preterm and term infant at birth and in the first weeks of life. Also, the drug elimination is slowed down in this subgroup of children, due to immaturity of both metabolic pathways and renal function. 

Age-related changes in drug distribution have been reported. The apparent volume of distribution is somewhat larger in newborns and infants than in adults. The estimated volume of distribution of sulfa-methoxypyridazine in newborns and infants is 0.47 and 0.36 L/kg, respectively, whereas the values are 0.20-0.26 L/kg in children, adults, and elderly subjects. The volume of distribution of chlordiazepoxide is substantially larger in the elderly (0.52 L/kg) than in the young (0.42 L/kg). The age-related difference in the volume of distribution may be due to a difference in plasma protein binding and/or in the relative size of body compartments. 

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. 

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

Drug (and metabolite) Protein binding (%) M/P" Infant dose (%) Detectable in infant plasma Reported infant toxicity Ref. 

Fasting plasma (heparin) is the preferred specimen type. In newborns and infants blood should be collected immediately before the next scheduled feeding. Serum is generally derived from blood left to clot at room temperature, a process that leads to artifacts from deamination, loss of sulfiir-containing amino acids due to protein binding, con-... 

Lactation — The moderate protein-binding profile of FLB suggests that the infant may have measurable plasma concentrations if breast-fed. In addition, safety issues regarding rare aplastic anemia associated with FLB in patients with epilepsy may increase the theoretical risks of breastfeeding. 

Pregnancy and Lactation — No data are available on the pharmacokinetics of LEV in pregnancy. However, the low-protein-binding profile of LEV suggests that an infant will have measurable plasma concentrations if breastfed. The risk/benefit of breast-feeding needs to be discussed with the mother. 

Lactation — Because of the high protein binding of PHT, an infant does not have measurable PHT plasma concentrations if the mother is taking therapeutic doses of PHT. ... 

Lactation — Based on the high-protein-binding characteristic of TGB, infants may not have measurable plasma concentrations when the mother is receiving doses of TGB. However, there are no data available. 

Lactation — Based on the protein-binding profile of ZON = 0.60), infants may have clinically significant plasma concentrations if breast-fed by mothers taking therapentic doses of ZON. The risk/benefit of breastfeeding needs to be discnssed with the mother. 

Plasma levels increased to reach a steady state concentration in the range 100-150 ng/ml. Milk concentrations were more varied. In 2 mothers levels remained low with values for diazepam of 17-19 ng/ml and desmethyidiazepam 39-52 ng/ml. In the other 2 subjects the diazepam and desmethyidiazepam concentrations rose to 43 ng/ml and 85 ng/ml respectively. The higher concentrations of desmethyidiazepam in milk probably reflect reduced protein binding. Oxazepam was not found in the milk. It is calculated that if a nursing mother takes 10 mg/day of diazepam, then the infant will receive at the most 45 pg of active drug in 500 g of milk. 

Z Uptake of bilirubin by the liven Bilirubin is only slightly soluble in plasma and, therefore, is transported to the liver by binding non-covalently to albumin. [Note Certain anionic drugs, such as salicylates and sulfonamides,1 can displace bilirubin from abu-min, permitting bilirubin to enter the central nervous system (CNS). This causes the potential for neural damage in infants.] Bilirubin dissociates from the carrier albumin molecule and enters a hepatocyte, where it binds to intracellular proteins, particularly the protein ligandin. 

Transferrin is one of the proteins responsible for binding and transporting both iron and manganese throughout the body. One study (Vahlquist et al. 1975) reported no correlation between infant cord blood and maternal blood transferrin levels. The same study reported an increase in plasma transferrin from 1.68-H/-0.60 mg/mL in blood from infants at 6 weeks of age, to a peak of 2.60+1-0.21 mg/mL at 10 months, with values stabilizing at these adult levels throughout 16 years of age. The authors did not comment as to the statistical difference, if any, of these values. 

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