Factors Influencing the Serum Concentration of Antiepileptic Drugs-Relationship between the Serum Valproic Acid Concentration and Daily Dose in Epileptic Patients.

Fukuoka, Noriyasu; Tsukamoto, Toyohisa; Uno, Junji; Kimura, Michio; Morita, Satoru

doi:10.5649/jjphcs1975.24.652

Cited by 4 publications

(3 citation statements)

References 4 publications

(4 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In this study, we assumed that C t was expressed as a power function of the daily dose per extracellular water volume and investigated which concomitant antiepileptic drugs aŠected C t using a power function, in the same way as we investigated for valproic acid (VPA). 11,12) We showed the eŠects of concomitant antiepileptic drugs on C t quantitatively, making it possible to estimate the changes in C t values without grouping by other factors when the concomitant antiepileptic drugs are changed. …”

Section: Introductionmentioning

confidence: 99%

Effects of Concomitant Antiepileptic Drugs on Serum Carbamazepine Concentration in Epileptic Patients: Quantitative Analysis Based on Extracellular Water Volume as a Transforming Factor

Fukuoka

Tsukamoto

Uno³

et al. 2003

YAKUGAKU ZASSHI

Self Cite

View full text Add to dashboard Cite

The eŠects of concomitant antiepileptic drugs on the serum carbamazepine concentration (C t ) were analyzed quantitatively. Primidone (PRM), phenobarbital (PB), phenytoin (PHT), valproic acid (VPA), zonisamide (ZNS), clonazepam (CZP), and ethosuximide (ETS) were coadministered with carbamazepine (CBZ). Routine therapeutic drug monitoring data, obtained from epileptic patients who were treated with the repetitive oral administration of CBẐ ne granules/tablets, were used for the analysis. A total of 119 patients were administered CBZ alone, and 91, 39, 19, and 6 patients were coadministered one, two, three, and more than four diŠerent antiepileptic drugs, respectively. Using the data obtained from the patients administered CBZ alone, C t could be expressed approximately as a function of the daily dose per extracellular water volume (D/V ECW ) as C t ＝A(D/V ECW ) B (A, B: parameter). By comparing the regression line on log C t vs. log(D/V ECW ) for CBZ alone with that for CBZ plus another concomitant drug, C t was thus found to be aŠected at each deˆnite ratio by PB and PHT, but not by VPA and ZNS. We postulated a model showing that C t is aŠected by each concomitant antiepileptic drug i at each deˆnite ratio. We deˆned the parameter R i (i＝1, 2, …, 7) representing the eŠect of each concomitant antiepileptic drug on C t . A linear polynomial expression, in which both members of this model are converted into common logarithms, was used for a multiple regression analysis. The analysis claried that PB and PHT lowered C t to 0.770 and 0.710 the value of CBZ alone, respectively. On the other hand, VPA and ZNS did not aŠect C t . The number of patients coadministered PRM, CZP, and/or ETS was not su‹cient to detect the eŠect on C t based on a test of signiˆcance. In the case of the addition or discontinuation of concomitant antiepileptic drugs in the same patient, the estimated C t values were calculated using the value of each R i and compared with the measured C t values. Both values were in good agreement, and thus our results appear valid.

show abstract

Section: Introductionmentioning

confidence: 99%

Effects of Concomitant Antiepileptic Drugs on Serum Carbamazepine Concentration in Epileptic Patients: Quantitative Analysis Based on Extracellular Water Volume as a Transforming Factor

Fukuoka

Tsukamoto

Uno³

et al. 2003

YAKUGAKU ZASSHI

Self Cite

View full text Add to dashboard Cite

show abstract

“…4 to elevate the power of the test and to estimate the more precise influence of each drug, quantitatively. (4) where L/D (meas) is the measured L/D ratio and L/D (0) is the L/D ratio of ZNS alone. R i is a parameter representing the influence of each antiepileptic drug on the L/D ratio of ZNS alone.…”

Section: Zns Alone Correlation Of L/d Ratio With Sex and Age As Shown Inmentioning

confidence: 99%

“…The authors showed that ideal body weight or extracellular water volume (V ECW ) could be used as a transforming factor to relate the serum concentration with the daily dose without an effect by confounding factors for valproic acid (VPA) 4) or carbamazepine (CBZ), 5) respectively. The influences of concomitant drug use on the serum concentration were evaluated quantitatively in all the patients without them being grouped by other confounding factors.…”

mentioning

confidence: 99%

Influence of Coadministered Antiepileptic Drugs on Serum Zonisamide Concentrations in Epileptic Patients: Quantitative Analysis Based on Suitable Transforming Factor

Fukuoka

Tsukamoto

Uno³

et al. 2003

Biological & Pharmaceutical Bulletin

Self Cite

View full text Add to dashboard Cite

Zonisamide (ZNS) is frequently added on conventional epileptic therapy for refractory seizures.1) It is clinically important to clarify the influences of antiepileptic drugs on the serum ZNS concentration in a steady-state (C t ).Before investigating the influences on C t , it is preferable to clarify the relation between daily dose (D) and C t in the administration of ZNS alone. C t and D are expressed as a function of clearance. Body weight (W) or body surface area, corresponding to clearance, has been used as a substitute for clearance (transforming factor). D is transformed to a variable (transformed daily dose: DЈ) being divided by a transforming factor, C t is thus related to DЈ.The influences of antiepileptic drugs on C t /DЈ (level/dose (L/D) ratio) have been examined, but no regard has been paid to the influences of confounding factors such as age and sex. Employing W as a transforming factor, the L/D ratio (C t /(D/W) : C t /D W Ј ) was found to be dependent on age.2) The analyses based on C t /D W Ј were misleading because the patients might be grouped by age.3) If DЈ, which was related to C t without being affected by confounding factors, could be determined, it would be worth evaluating for clinical use.The authors showed that ideal body weight or extracellular water volume (V ECW ) could be used as a transforming factor to relate the serum concentration with the daily dose without an effect by confounding factors for valproic acid (VPA) 4) or carbamazepine (CBZ), 5) respectively. The influences of concomitant drug use on the serum concentration were evaluated quantitatively in all the patients without them being grouped by other confounding factors. 6,7) In this paper, V ECW also affected the L/D ratio of ZNS independent of confounding factors. Then the authors detected the drug affecting the L/D ratio and investigated its influence quantitatively. METHODSWe collected data from epileptic patients, who were chronically treated with multiple oral administrations of ZNS (Excegran ® granules/tablets, Dainippon Pharmaceutical Co., Osaka, Japan) at Kagawa Medical University Hospital between April 1995 and May 1998 and at Kurashiki Central Hospital between April and September 1996. The total number of patients administered ZNS was 175. Patients with abnormal findings on hepatic and renal function tests were excluded. Blood samples were drawn 2 to 3 h after the last dosing in outpatients and 2 to 15 h in inpatients. The fluctuations of C t at different sampling times were considered to be negligible because of its long elimination half-life. 8)When there were multiple measurements for C t in one patient with the same prescribed drugs during the study period, the average value was used. The age, body weight, height and daily ZNS dose were treated in the same manner. When several varieties of drugs were prescribed in one patient, the count was taken as the number of patients. In both hospitals, C t was measured in duplicate by HPLC and the average value employed.Data analysis was performed by utilizing a sta...

show abstract

Valproic Acid and Sodium Valproate: Comprehensive Profile

Alsarra

Al-Omar

Belal

2005

Profiles of Drug Substances, Excipients and Related Methodology

View full text Add to dashboard Cite

Factors Influencing the Serum Concentration of Antiepileptic Drugs-Relationship between the Serum Valproic Acid Concentration and Daily Dose in Epileptic Patients.

Cited by 4 publications

References 4 publications

Effects of Concomitant Antiepileptic Drugs on Serum Carbamazepine Concentration in Epileptic Patients: Quantitative Analysis Based on Extracellular Water Volume as a Transforming Factor

Effects of Concomitant Antiepileptic Drugs on Serum Carbamazepine Concentration in Epileptic Patients: Quantitative Analysis Based on Extracellular Water Volume as a Transforming Factor

Influence of Coadministered Antiepileptic Drugs on Serum Zonisamide Concentrations in Epileptic Patients: Quantitative Analysis Based on Suitable Transforming Factor

Valproic Acid and Sodium Valproate: Comprehensive Profile

Contact Info

Product

Resources

About