patent ductus arteriosus - Patent ductus arteriosus, or PDA, is a heart condition that is normal but reverses soon after birth. In a persistent PDA, there is an irregular transmission of blood between two of the most important arteries in close proximity to the heart, the aorta and the pulmonary artery Necrotizing enterocolitis (NEC) is a medical condition primarily seen in premature infants ,  where portions of the bowel undergo necrosis (tissue death).
, many of the physiologic and pharmacologic principles discussed above also apply to term infants.
The UDP-glucuronyl transferase enzyme system of infants, especially premature infants, is immature and incapable of metabolizing the excessive drug load. Insufficient renal excretion of the unconjugated drug.
1.Most pathways of drug clearance (hepatic and renal) are mature, with clearance often exceeding adult values. Changes in clearance of a drug may be dependent on maturation of specific metabolic pathways.
The total volume of blood is estimated at 80 to 90 ml/kg body weight; 3% is 2.4 ml blood per kg body weight.
Dose calculation errors occur in measuring height n weight
(b) Relative bioequivalence comparisons of the paediatric formulation with the adult formulation performed in adults, and
(c) Definitive pharmacokinetic studies for dose selection across the age ranges of paediatric patients in whom the drug is likely to be used. These studies should be conducted in the paediatric patient population with the disease under study.
Evolving cognitive and emotional changes could potentially influence the outcome of clinical studies.
Many diseases are also influenced by the hormonal changes around puberty (e.g., increases in insulin resistance in diabetes mellitus, recurrence of seizures around menarche , changes in the frequency and severity of migraine attacks and asthma exacerbations).
Hormonal changes may thus influence the results of clinical studies.
The toxicity of some excipients may vary across pediatric age groups and between pediatric and adult populations, e.g., benzyl alcohol is toxic in the preterm newborn.
Depending on the active substance and excipients, appropriate use of the medicinal product in the newborn may require a new formulation or appropriate information about dilution of an existing formulation .
Timing of sampling should be co-ordinated as far as possible to avoid repeated procedures and sampling during the day in order to minimize pain and distress, and the risk of iatrogenic complications.
Timing of sampling and number of sampling attempts should be defined in the protocol. For example, it is recommended that after one unsuccessful attempt, another experienced person take over the procedure.
Preterm and term neonates have very limited blood volume, are often anaemic due to age and frequent sampling related to pathological conditions.
The fact that children, especially in this age group, receive blood transfusions (or iron or erythropoietin supplementation) should not be used as a convenience for increased volume or frequency for blood sampling.
Per individual, the trial-related blood loss (including any losses in the manoeuvre) should not exceed 3 % of the total blood volume during a period of four weeks and should not exceed 1% at any single time.
In the rare case of simultaneous trials, the recommendation of 3% remains the maximum.
Monitoring of actual blood loss is routinely required in preterm and term neonates.
When a medicinal product is studied in pediatric patients in one region, the intrinsic (e.g., pharmacogenetic) and extrinsic (e.g., diet) factors that could impact on the extrapolation of data to other regions should be considered.
Obtaining knowledge of the effects of medicinal products in pediatric patients is an important goal. However, this should be done without compromising the well-being of pediatric patients participating in clinical studies.
Lamivudine therapy is effective for chronic hepatitis B infection in adults. We evaluated the efficacy and tolerability of lamivudine as a treatment for chronic infection with hepatitis B virus (HBV) in children.
Children with chronic hepatitis B were randomly assigned in a 2:1 ratio to receive either oral lamivudine (3 mg per kilogram of body weight; maximum, 100 mg) or placebo once daily for 52 weeks. The primary end point was virologic response (defined by the absence of serum hepatitis B e antigen and serum HBV DNA) at week 52 of treatment.
Of the 403 children screened, 191 were randomly assigned to receive lamivudine and 97 to receive placebo. The rate of virologic response at week 52 was higher among children who received lamivudine than among those who received placebo (23 percent vs. 13 percent, P=0.04). Lamivudine therapy was well tolerated and was also associated with higher rates of seroconversion from hepatitis B e antigen to hepatitis B e antibody, normalization of alanine aminotransferase levels, and suppression of HBV DNA.