| Sodium Valproate의 적정용법에 대한 약력학적 접근
-One Point Method에 의한 Sodium Valproate의 적정유지용량예측- |
| 홍승봉, 이광우 , 노재규, 이상복, 명호진, 신상구, 박찬웅, 김진규 |
| 서울대학교 신경과, 약리학, 임상병리학. |
| Pharmacokinetic Approach for the Optimum Administration of Sodium? Valproate
- Maintenance Dose Prediction of Sodium Valproate Based on One ?Point Method- |
| Seung-Bong Hong, M.D., Kwang-Woo Lee, M.D., Jae-Kyu Roh, M.D., Sang-Bok Lee, M.D., Ho-Jin Myung, M.D.,Sang-Goo Shin, M.D.*, Chan-Woong Park, M.D.*, Jin Q Kim, M.D.** |
| Department of Neurology, Pharmacology* & Clinical Pathology**, College of Medicine, Seoul National University |
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| Abstract |
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To assess prospectively the predictability of optimum maintenance dose based on valproic acid (VPA) concentration after a single dose (one point method), 47 patients of seizure disorder were given Sodium Valproate (Na Val.).
The investigation consisted of two phases, the first with a kinetic and fixed-dose
design and the second designed for prospective maintenance dose adjustment based on
the single dose VPA level. During the first phase, 27 subjects (12 women, 15 men)
received a single, oral dose of 600mg Na Val. At 4 pm. Blood samples (5 ml) were
drawn 18 hours after dosing. This was followed by a fixed 900mg dose of Na Val. In
three daily doses for 2 weeks. Blood samples (5ml) for VPA assay were drawn 5 hours
after dosing on days 10.
Between plasma levels after the single oral dose and mean steady-state levels in
the patients, a good correlation was shown by linear regression analysis. Nomogram for
dosage requirement that would achieve an optimum therapeutic steady-state
concentration of 75 ug/ml , was derived from the linear regression equation.
In the second phase of the study, 20 subjects (11 women, 9 men) received a single
dose of 600mg Na Val. At 4 pm. A blood sample for VPA assay was drawn 18 hours
after dosing. Maintenance dose requirement was calculated from the nomogram for the
18-hour results. Subjects received the adjusted dose of Na Val. In three daily doses.
Drug levels to assess the steady-state were measured 5 hours after last dosing on days
10 after institution of the predicted dose. And the results are summarized as follows:
1. Between 18-hr VPA plasma levels and steady-state levels, a strong correlation was
shown by linear regression analysis (r=0.84; P[t]<0.001).
2. In the second phase of study, subjects who were given predicted maintenance dose
from the nomogram for the 18-hr results, achieved a mean steady-state VPA plasma
level of 77.87 ug/ml after 10 days, with 80% of the levels falling within 2 S.D. range
(73.26+2x8.56) of expected levels.
3. 90% of measured steady-state levels was within the therapeutic range (50-100ug/ml)." |
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