Bioavailability pediatric patients

Drug absorption is highly variable in neonates and infants [21,22]. Older children appear to have absorption patterns similar to adults unless chronic illness or surgical procedures alter absorption. Differences in bile excretion, bowel length, and surface area probably contribute to the reduced bioavailability of cyclosporine seen in pediatric liver transplant patients [22a]. Impaired absorption has also been observed in severely malnourished children [22b]. A rapid GI transit time may contribute to the malabsorption of carbamazepine tablets, which has been reported in a child [23]. Selection of a more readily available bioavailable dosage form, such as chewable tablets or liquids, should be promoted for pediatric patients. 

Patients younger than 3 months of age - The half-life was about 13 hours. In neonates 14 days of age or less, bioavailability was greater, total body clearance was slower, and half-life was longer than in pediatric patients more than 14 days old. 

Lerner et al. [91] also studied the pharmacokinetics of darbepoietin alfa in pedisatric patients with chronic kidney disease (CKD). Twelve patients 3-16 years of age with CKD were randomized and received a single 0.5pg/kg dose of darbepoietin alfa administered i.v. or s.c. After a 14- to 16- day washout period, patients received an identical dose of darbepoietin alfa by the alternate route. After i.v. administration, the mean clearance of darbepoietin alfa was 2.3mL/h/kg with a mean terminal half-life of 22.1 h. After s.c. administration, absorption was rate limiting, with a mean terminal half-life of 42.8h and a mean bioavailability of 54%. Comparison of these results with those from a previous study of darbepoietin alfa in adult patients [89] indicated that the disposition of darbepoietin alfa administered i.v. or s.c. is similar in adult and pediatric patients, although absorption may be slightly more rapid in pediatric patients after s.c. dosing. 

The sodium salt of valproate is marketed in Europe as a tablet and is quite hygroscopic. In Central and South America, the magnesium salt is available, which is considerably less hygroscopic. The free acid of valproate was first marketed in the USA in a capsule containing corn oil the sodium salt is also available in syrup, primarily for pediatric use. An enteric-coated tablet of divalproex sodium is also marketed in the USA. This improved product, a 1 1 coordination compound of valproic acid and sodium valproate, is as bioavailable as the capsule but is absorbed much more slowly and is preferred by many patients. Peak concentrations following administration of the enteric-coated tablets are seen in 3-4 hours. Various extended-release preparations are available not all are bioequivalent and may require dosage adjustment. 

Many drugs can now be delivered rectally instead of by parenteral injection (intravenous route) or oral administration. Generally, the rectal delivery route is particularly suitable for pediatric and elderly patients who experience difficulty ingesting medication or who are unconscious. However, rectal bioavailabilities tend to be lower than the corresponding values of oral administration. The nature of the drug formulation has been shown to be an essential determinant of the rectal absorption profiles. The development of novel absorption enhancers with potential efficacy without mucosal irritation (low toxicity) is very important. The delivery of peptide and protein drugs by the rectal route is currently being explored and seems to be feasible. 

Most medications have shorter half-lives in children than in adults, and therefore children may need sustained-release products to maintain serum concentrations in the therapeutic range. For example, a sustained-release theophylline product may be needed for a child with asthma. It may need to be administered every 8h to the child as compared to every 12 h for a healthy, non-smoking adult to maintain therapeutic serum concentrations. When choosing a sustained-release theophylline preparation for a child, it must be remembered that because of differences in release properties, theophylline sustained-release products are not interchangeable. A product selected for the pediatric asthma patient should be reliably absorbed with a minimal serum concentration variation and not a preparation that has exhibited a difference in bioavailability when administered with or without food.[ > - ]... 

Most oral formulations are solid tablets or capsules, but there are many solution formulations for oral administration that are filled into capsules, or are bulk solutions such as oral solutions, syrups, and elixirs. The reasons for pursuing a solubilized oral formulation include enhancing the oral bioavailability of a poorly water-soluble drug, a drug molecule that is an oil, a low dose drug (i.e., pediatric formulation, a measurable formulation for dose modification, a formulation for patients who cannot swallow tablets... 

Patients having outpatient surgical procedures who experience moderate to moderately severe pain are frequently prescribed an oxycodone product as soon as oral intake is possible. The drug has high oral bioavailability and is well absorbed as either a tablet or elixir. Oxycodone oral solution is particularly useful to treat post-operative pain in children in the outpatient setting. Like many drugs used for children, oxycodone has not been approved for pediatric use by the FDA. 

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