Factors Influencing Serum Concentration of Zonisamide in Epileptic Patients.

Kimura, Masahiko; Tanaka, Naomi; Kimura, Yasuhiro; Miyake, K.; Kitaura, Teruaki; Fukuchi, Hiroshi; Harada, Yuka

doi:10.1248/cpb.40.193

Cited by 13 publications

(5 citation statements)

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“…Zonisamide protein binding was investigated using ultrafiltration (Amicon Centrifree Micropartition System; temperature not stated) in six healthy volunteers, and a mean ± SD binding of 39.4 ± 1.2 was observed; this concurred with a value of 40–50% quoted in the SPC. Using the same methodology as in this previous study and at a temperature of 25°C, we found a mean percentage binding of 43.7 (Table ).…”

Section: Discussionsupporting

confidence: 67%

Serum protein binding of 25 antiepileptic drugs in a routine clinical setting: A comparison of free non–protein‐bound concentrations

et al. 2017

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Section: Discussionsupporting

confidence: 67%

Serum protein binding of 25 antiepileptic drugs in a routine clinical setting: A comparison of free non–protein‐bound concentrations

et al. 2017

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“…Ojeman et al [195] investigated the influence of CBZ and PHT on the pharmacokinetics of a single dose of zonisamide in patients with epilepsy. The plasma half-life of zonisamide was significantly longer in patients concurrently taking CBZ (36.4 h) than in those taking PHT (27.1 h), but both values were shorter than the half-life values usually found after administration of single oral doses of zonisamide in healthy volunteers (50-68 h VPA marginally increased the free fraction of zonisamide in humans [197].…”

Section: Eflkct Of Other Drugs On the Pharmacokinetics Of Zonisamidementioning

confidence: 75%

Enzyme induction and inhibition by new antiepileptic drugs: a review of human studies

Benedetti¹

2000

Fundamemntal Clinical Pharma

120

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The aim of this paper is to review a number of new antiepileptic agents (i.e. felbamate, gabapentin, lamotrigine, levetiracetam, oxcarbazepine, tiagabine, topiramate, vigabatrin and zonisamide) for their inducing and/or inhibitory properties in humans, mainly considering the interactions where they are involved as the cause rather than the object of such interactions. Two aspects have been particularly taken into account: the changes or absence of changes in plasma/serum concentrations of concomitant drugs and the direct or indirect evidence of induction, inhibition or lack of effect on the six major human hepatic CYP isozymes (CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP2E1 and CYP3A4), as well as on other CYP isozymes or enzyme systems. Felbamate clearly affects the pharmacokinetics of a number of drugs, generally increasing but also decreasing their concentrations. It induces enzymes such as CYP3A4 and inhibits enzymes such as CYP2C19 and those of the beta-oxidation pathway. Topiramate is not devoid of potential interaction properties: it decreases the plasma concentrations of ethinylestradiol, induces CYP3A4 and inhibits CYP2C19. For oxcarbazepine, no inhibitory, only inductive effects have been observed thus far. Felbamate. topiramate and oxcarbazepine may induce the metabolism of steroidal oral contraceptives. In this respect, tiagabine has been studied at a rather low dose. Pharmacodynamic or pharmacokinetic interaction seems to exist between lamotrigine and carbamazepine. Lamotrigine appears to be a weak inducer of UGTs, whereas induction of CYP3A4 seems improbable as the compound does not change the concentrations of oral contraceptives or the urinary excretion of 6beta-hydroxycortisol. Zonisamide has very peculiar pharmacokinetics and an extensive metabolism. Additional information on its enzyme inducing or inhibiting properties would be necessary, as data so far collected on its effect on the pharmacokinetics of other drugs are conflicting. Gabapentin, vigabatrin and in particular levetiracetam appear to be devoid of significant enzyme inducing or inhibiting properties.

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“…15) We do not have enough data to elucidate the intra-individual relationship. However, a linear relationship for ZNS alone 2) and concomitant use of ZNS 3) was also reported. In the present study, a significant linear relationship was found between C t and D ECW Ј , and concomitant therapy changed only the slope of the regression line (Fig.…”

Section: Discussionmentioning

confidence: 99%

“…The increase, however, was small and significant linear relationships were also reported between total and unbound serum concentrations of ZNS on the administration of ZNS alone and ZNSϩVPA. 2,3) The clinical efficacy of ZNS would unlikely be affected by VPA. Though each R i was calculated from the total concentration, it sufficiently corresponds to the change in the un- bound concentration and is closely associated with clinical efficacy.…”

Section: Discussionmentioning

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

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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...

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Factors Influencing Serum Concentration of Zonisamide in Epileptic Patients.

Cited by 13 publications

References 0 publications

Serum protein binding of 25 antiepileptic drugs in a routine clinical setting: A comparison of free non–protein‐bound concentrations

Serum protein binding of 25 antiepileptic drugs in a routine clinical setting: A comparison of free non–protein‐bound concentrations

Enzyme induction and inhibition by new antiepileptic drugs: a review of human studies

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

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