Pharmacokinetics includes the absorption, distribution, metabolism and excretion of drugs (pharmacokinetics). Absorption The absorption from the gastrointestinal tract is affected by gastric acid secretion bile salt formation gastric emptying time intestinal motility intestinal length and effective resorbing surface microbial flora are reduced all these factors Neonates (whole pregnancy or born prematurely) and can be both reduced and occur more frequently when a sick child of any age. A reduced secretion of gastric juice increased the bioavailability of acid-sensitive drugs (eg. As penicillin) and reduces the bioavailability of weakly acidic drugs (eg., Phenobarbital). A decreased bile salt formation reduces the bioavailability of lipophilic drugs (eg. Diazepam). Delayed gastric emptying and decreased intestinal motility extend in administering enteral medications to children <3 months the time required to achieve therapeutic drug levels. Another reason for reduced drug absorption present in the intestines of young infants metabolizing enzymes may be. Infants with congenital atretischem intestine or surgically removed bowel or those that have Jejunumkatheter may possibly suffer from certain resorptive disorders, depending on the extent and location of the intestinal loss or intestinal catheter. The absorption of injected drugs is often different. Possible causes include variability in their chemical properties differences in absorption at the site of injection (IM or SC) variability in muscle mass in children disease (z. B. decreased Kreislauffunkton) variability of the injection depth (too deep or too shallow) Intramuscular injections in children usually avoided because they are painful and can lead to tissue damage. but if a i.m. Injection is required, water-soluble drugs should be chosen because they do not precipitate at the injection site. The transdermal absorption may be enhanced in neonates and young infants, on the one hand due to the thin stratum corneum, on the other hand because of the much larger ratio of body surface area to weight compared to older children and adults. Skin lesions (eg. As abrasions, eczema, burns) enhance the absorption in children of all ages. Transrectal drug treatment is usually appropriate only in emergency situations when a I.V. Access is not available (eg., Rectal administration of diazepam in status epilepticus). The localization of the medication into the rectum can affect the absorption, since there are differences in venous outflow. Young infants can also repel before significant absorption has taken place the drug. The absorption of drugs into or out of the lungs (for. Example, ?-agonists in asthma, Surfactant at acute respiratory syndrome) varies less due to physiological parameters as a much more concerning the reliability of the application device and the application technology of the patient or the caregiver , Drug distribution in the body, the volume of drug distribution in the body depends in children of age. Therefore, this age-related differences occur because the body composition changes (v. a. with respect to the extracellular total body water content) and plasma protein binding. With younger children, higher doses (changes in body composition related to growth and maturation s.) Are to be administered (per kg body weight) for the water-soluble drugs, since a large portion of her body consists of water. Conversely, one needs to avoid toxicity in children aging lower doses due to the decreasing water content. Changes in body composition related to growth and maturation Adapted from Puig M: Body composition and growth. In Nutrition in Pediatrics, ed. 2, ed. WA and Walker JB Watkins. Hamilton, Ontario, BC Decker, 1996. Many drugs bind to proteins (primarily albumin, ?1-acid glycoprotein, and lipoproteins); protein binding limits the distribution of free substance throughout the body. The albumin and total protein concentration are lower in newborns, but reach the level of adults aged 10 to 12 months. Decreased plasma binding is also caused in newborns by qualitative differences in the binding proteins and by competitive binding of molecules such as bilirubin and free fatty acids circulating in neonates and infants in higher concentrations. This, however, also more frequent side effects results in an increased concentration of free drug, a greater availability of the drug at the receptor as well as the one hand, desired pharmacological effects, on the other hand, at lower concentrations. Metabolism and excretion The metabolism and excretion of drugs vary with age and depend on the substance and the drug. Most drugs, v. a. Phenytoin, barbiturates, analgesics, and cardiac glycosides have but in newborns compared to adults, a 2 to 3 times longer plasma half-life. The cytochrome P450 (CYP 450) enzyme in small intestine and in the liver is the most important known system for the metabolism of drugs. CYP450 enzymes inactivate drugs oxidation, reduction and hydrolysis (phase I reaction) hydroxylation and conjugation (phase II reaction) The Phase I activity is reduced in newborns, then rises continuously during the first six months of life, exceeds for some drugs, the rate adult in the first years, slows during adolescence and levels off at the end of puberty to adult values. For some drugs, the metabolic rate can correspond to that of adults after two to four weeks. The activity of CYP450 can also by additional drugs increase (decrease in the concentration and effect) or be inhibited (increased concentration and effect). These interactions can lead to drug toxicity when the CYP450 activity inhibited or inadequate drug levels is induced in CYP450 activity. The kidneys, lungs and skin play as well as intestinal metabolizing enzymes in newborns as part of the metabolism of some drugs involved. The phase II reaction varies considerably from substance to substance. The maturation of the responsible for the metabolism of bilirubin and paracetamol enzymes is delayed; the enzymes for conjugation of morphine are even fully developed already in preterm infants. The metabolites of drugs are primarily excreted via the bile or kidneys. Renal elimination plasma protein binding renal blood flow Glomerular filtration rate (GFR) Tubular secretion All these factors undermine changes in the first two years of life. Renal blood flow is low at birth (12 ml / min) and reaches adult levels of 140 ml / min at the age of one year. The situation is similar with the GFR with an increase of 2-4 ml / min at birth to 8-20 ml / min at the age of 2-3 days and adult levels of 120 ml / min at the age of 3-5 months. Drug dosage Due to the above factors, the dosage in children <12 years always a matter of age, body weight, or both. While this approach may be pragmatic, but is not ideal. Even in populations with children of a similar age or weight, the doses required may differ in the absorption, metabolism and elimination because of maturity differences. Therefore, it is desirable, where practicable, adjust dosages based on the plasma levels (although the plasma concentration can not be the drug concentration in the target organ reflect). Unfortunately, these adjustments are not possible with most drugs. In the USA, after the enforced in the US federal legislation (the Best Pharmaceuticals for Children Act of 2001 and the Pediatric Research Equity Act of 2003 [both 2012 renewed]) studies carried out, which resulted in dose recommendations for> 450 drugs that does not have a pediatric had dosing information.


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