Essentials for starting a pediatric clinical study (1) : Pharmacokinetics in children
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概要
- 論文の詳細を見る
During childhood, as the body weight and its function changes drastically by age, drug therapy should be arranged according to the age-related changes in pharmacokinetics of its age. The gastric absorption of oral drugs is affected by the high pH of gastric juice in newborns and slow gastric emptying up to six months of age, resulting generally in poor absorption except for lipophilic drugs. Intestinal absorption is also poor in newborns. Due to the low serum protein level, the protein binding ratio is low in newborns, though the serum protein level increases to the adult level at one to three years after birth. Drug metabolism capability generally develops quickly after birth and reaches the adult level in two to three years, though there are many exceptions. The CYP3A7 activity is relatively high just after birth, which affects the clearance of its substrate drugs. In terms of conjugation enzyme activities, sulfate conjugation develops fast and glucuronate conjugation develops slowly. Among the glucuronosyltransferase (UGT) enzymes, UGT1A1 and UGT2B7 reach the adult level by 3 months of age, whereas UGT1A6, UGT1A9 and UGT2B7 take a few years to ten years. Although there is no definitive report on enzyme induction ability, both CYP and UGT are suggested to be more inducible in children than in adults. The hepatic drug metabolism of children is characterized by the fact that the relative liver weight and hepatic blood flow rate per unit liver weight is larger in children than in adults. Drug excretion from the kidney is undeveloped in newborns, below 50% of the adult level up to the age of two to three months. Therefore, the effective dose range and toxic dose range of drugs is closer in such young subjects, but reaches adult level by the age of one year. The glomerular filteration rate is low in newborns, and rapidly increases up to 200% of that in adults in one year, and then gradually decreases to the adult level. As mentioned above, newborns, infants and children show different pharmacokinetics for different drugs and therefore cannot always be discussed in the same way. For the safe use of drugs, the pharmacokinetics data of each drug should be considered.
- 日本トキシコロジー学会の論文
著者
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Yokoi Tsuyoshi
Drug Metabolism And Toxicology Division Of Pharmaceutical Sciences Graduate School Of Medical Scienc
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Yokoi Tsuyoshi
Drug Metabolism And Toxicology Division Of Pharmaceutical Sciences Kanazawa University
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