2024-03-28T08:04:00Z
https://u-ryukyu.repo.nii.ac.jp/oai
oai:u-ryukyu.repo.nii.ac.jp:02016189
2022-02-22T04:16:34Z
1642838163960:1642838198944:1642838199408:1642838220226
1642838403551:1642838412624
[総説]パルプロ酸の薬物,代謝動態 : 催奇怪予防の観点から
Pharmacokinetics and metabolism of valproate : In relation to prevention of valproate teratogenicity
近藤, 毅
Kondo, Tsuyoshi
valproate
teratogenicity
polypharmacy
pharmacokinetics
metabolism
Pharmacokinetics and metabolism of valproate (VPA) has been discussed in relation to the risk and prevention of VPA teratogenicity. Prospective epidemiological studies have shown that high VPA dosages (≧1000 mg/day) and high VPA concentrations (≧ 70$ \mu $g/ml) together with VPA polypharmacy (especially coadministration with enzyme-inducing antiepileptic drugs) are regarded as clinical risk factors for increased VPA teratogenicity. An animal experiment has also shown that high peak concentration after single dosing of VPA during the early stage of pregnancy correlates well with the incidence of neural tube defects. All of these risk factors enhance metabolic conversion from VPA to its toxic metabolite, 2-propy1-4-pentenoic acid (4-en). On the other hand, the use of slow-release formulation of valproate (VPA-SR) results in reduced formation of 4-en as well as decreased diurnal fluctuations in VPA concentrations. These pharmacokinetic and metabolic alterations by using VPA-SR may be helpful in reducing VPA teratogenicity. We therefore recommend that high VPA dosages, high VPA concentrations and VPA polypharmacy should be avoided in epileptic women of childbearing age. Conventional VPA, when used in these subjects, should be replaced with VPA-SR before pregnancy to diminish the risk of VPA teratogenicity.
論文
http://purl.org/coar/resource_type/c_6501
琉球医学会
Ryukyu Medical Association
VoR
1346888X
0289-1530
AN10369445
琉球医学会誌 = Ryukyu Medical Journal
3
23
77
71
jpn
open access
琉球医学会