Advantage of Body Surface Area on Dose Adjustment of Antiepileptic Drugs.

Uno³

et al. 2003

YAKUGAKU ZASSHI

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.

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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

Uno³

et al. 2003

YAKUGAKU ZASSHI

show abstract

“…1) , where the CBZ binding to plasma proteinn) was Eqs. (4), (5) and (6) are the basic equations for the CBZ pharmacokinetic behavior. Table 1 shows the characteristics of the patients administrated CBZ alone in each hospital.…”

Section: Discussionmentioning

confidence: 99%

“…Then an equation which expressed the relationship between Ct and D was derived from eqs. (4), (5) and (6)in the following procedure. Using 119 data shown in Fig.…”

Section: Multiple Regression Analysismentioning

confidence: 99%

Advantage of Extracellular Water Volume for the Relation between Serum Carbamazepine Concentration and Transformed Daily Dose.

Japanese Journal of Hospital Pharmacy

Uno

et al. 2000

We conducted a study to clarify the most suitable factors related to the carbamazepine daily dose (D) with the serum concentration (Ct). Therapeutic drug monitoring data obtained from epileptic patients who were chronically treated with single and repetitive oral administrations of carbamazepine (CBZ). The 119 steadystate data were used. First, when the extracellular water volume (VECW) was employed as a transforming factor, Ct/ (D/VECW) ratio was found to be independent of the patient's age. In addition, a multiple regression analysis revealed that Ct was dependent on only D/VECW. From these findings, we concluded that Ct could only be related with D/VECW. Next, a l-compartment model including two assumptions that CBZ binds to plasma protein and the distribution volume of free-CBZ is proportional to VECW, was postulated for our analysis. At steady-state, Ct was expressed as follows: (X=D/VECW. ƒ¿, Ka, Cbs: parameter) The parameter values were estimated by the nonlinear least squares method as a, Ka and Cbs were 0.013, 1.6 and 12.8, respectively. The plasma protein binding ratios were 92.3, 90.2 and 87.1(%) when the serum CBZ concentrations were 6,8 and 10[ƒÊg/mL], respectively. These values closely corrected with those reported previously. As a result, VECW is considered to be a suitable transforming factor for the relation between Ct and D, and our model seems to be approriate.

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“…Then the tangent line to the curve at X =0 was obtained using the estimated parameter values, which is shown in Fig. 2 (11) where the subscript s shows saturated situation. Employing the estimated parameter values of eq (10), we obtain Gs=0.177 Xs+156, which is also shown in Fig.…”

Section: Characteristics Of the Patientsmentioning

confidence: 99%

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

Japanese Journal of Hospital Pharmacy

Uno

et al. 1998