developmental pharmacology - nih clinical center - americas 发育药理学nih临床中心-美国.pptVIP

* Dose 16 to 30 mg/kg Circles grade 0 toxicity, squares grade 1, diamonds grade 2, upright triangles grade 3, and upside down triangles grade 4 regimen related toxicity. Age-dependent clearance of busulfan also has a direct impact on clinical outcome for this anticancer drug. Orally administered busulfan is a bifunctional alkylating agent that is an important component of bone marrow transplant preparative regimens. In children 5 years of age, the apparent clearance of busulfan is 2-3 fold higher than it is in adults, due to enhanced glutathione conjugation (primary route of elimination) in children . As a result, the steady state plasma concentrations of busulfan are lower in young children, and the incidence and severity of busulfan-related toxicity was also lower, but the graft rejection rate was significantly higher. Glutathione conjugation is primary elimination route * Cystic fibrosis is a multisystem inherited disorder that can effect major organs associated with drug disposition, including the GI track, pancreas, heart, liver and kidney. The PK of many drugs are altered in patients with CF, and, surprisingly, plasma concentrations are usually lower. Increased rates of clearance for a variety of drugs - both renally excreted and hepatically metabolized. The precise mechanism has not been identified The studies have resulted in dose recommendations in CF patients: 20-30% higher doses of beta-lactams and dose adjustments of aminoglycosides based on TDM. * * * * Difficult to make generalizations about the effect of development on the pharmacology of drugs used in newborns, infants and children. * At birth renal function is limited, because the kidney is anatomically and functionally immature. Renal blood flow in newborns is approximately 40 ml/min/kg in newborns which is about 16% of cardiac output. Within hours after birth there is a dramatic decrease in renal vasculature resistance and an increase in RBF. Adult values are reached by 1 year of age. GFR is a