Syoichi Yamashita

Simple and rapid analysis of lamotrigine, a novel antiepileptic, in human serum by high-performance liquid chromatography using a solid-phase extraction technique

A simple and rapid method for the quantitation of concentrations of lamotrigine, a novel antiepileptic, in human serum was developed with high-performance liquid chromatography, using a solid-phase extraction technique. The mobile phase was composed of acetonitrile-10 mM phosphate buffer (pH 3.5) containing 5 mM sodium octanesulphonate (27:73, v/v), and components were detected at 265 nm. Retention times of acetanilide as an internal standard and lamotrigine were 3.4 and 10.3 min, respectively. The coefficients of variation were 3.1-4.5% and 4.4-9.8% for the within-day and between-day precision estimates, respectively. The extraction recovery of lamotrigine added to blank serum was 86-107%. The quantitation limit of lamotrigine was ca. 0.2 microgram/ml in 100 microliters of serum. These results suggest that the method employed in this study is useful for the routine monitoring of serum concentrations of lamotrigine in epileptic patients.

Effects of various antiepileptic drugs on plasma levels of lamotrigine, a novel antiepileptic, in rats.

The pharmacokinetics of lamotrigine (LTG) and effects of carbamazepine (CBZ), valproic acid (VPA) and zonisamide (ZNS) on LTG kinetics were investigated in rats. LTG plasma levels were measured by high-performance liquid chromatography (HPLC). A single oral administration of LTG at 2.5-10 mg/kg showed linear disposition kinetics. In the pharmacokinetic parameters of LTG when combined with CBZ, the maximal plasma concentration (Cmax) and the area under the plasma concentration curve (AUC0-36) values were significantly lower and the time to maximal plasma concentration (Tmax) value was significantly higher than those in LTG alone. Furthermore, the Cmax and AUC0-36 values of LTG when pretreated with CBZ for 7 days were significantly lower than those from simultaneous treatment with CBZ. The Cmax and AUC0-36 values of LTG when combined with VPA were significantly lower than those for LTG alone. There was no significant difference in the Tmax or time of elimination half-life (t1/2) values of LTG between simultaneous and pretreatment with VPA. Of the pharmacokinetic parameters of LTG with ZNS combination, the Cmax value of LTG after long-term dosings of ZNS decreased significantly, whereas no significant change in Cmax was observed after the combined single administration of LTG and ZNS. Single and chronic ZNS treatment did not significantly affect the Tmax, t1/2 and AUC0-36 values of LTG. The LTG trough level was significantly reduced by CBZ administration, reached the bottom level at 6 days after starting CBZ administration, and recovered gradually after withdrawal of CBZ. These results suggest that CBZ, VPA and ZNS causes changes in the plasma LTG level. They also suggest that in therapy combining LTG with one of these antiepileptics, especially CBZ, the LTG concentration in plasma should be monitored carefully.

Ion-selective electrode for procainamide determination in blood serum

Abstract A procainamide-selective electrode was constructed and applied for the determination of procainamide concentration in blood serum. The detection limit was 1.5 μg ml−1, but determination down to 0.5 μg ml−1 was possible with an appropriate calibration. The results correlated well with those obtained by a fluorescence polarization immunoassay which is widely used for the determination of serum procainamide concentration. The present method is simple, rapid, economical and is unaffected by common cations present in blood and only slightly by N-acetylprocainamide, a metabolite of the drug. It is therefore useful for therapeutic drug monitoring in a clinical setting.

Anticonflict effects of acute and chronic treatments with buspirone and gepirone in rats.

The anticonflict activities of buspirone and gepirone were examined in the Vogels water licking test in rats. Acute treatment with buspirone induced a significant increase in water licking response, but gepirone showed slightly more marked effect than buspirone. The anticonflict activities of these compounds were potentiated by chronic administration. Especially, gepirone exhibited a dramatically remarkable anticonflict effect. These results suggest that gepirone has a great possibility of promising drug for anxiety.

Determination of plasma phenobarbital concentration by high-performance liquid chromatography in rat offspring.

Plasma phenobarbital (PB) concentrations in rat offspring were determined using a 9 microl capillary by high-performance liquid chromatography (HPLC). Capillary plasma which was put into a Bond Elut cartridge column by using 1 ml of 0.01 M KH2PO4 was applied to the column with 50 microl of 2 microg/ml of acetanilide (internal standard, I.S.). After washing the column, PB and I.S. were eluted with methanol and injected into the HPLC system. There were excellent linear correlation between the amount of PB and length of the capillary at three different concentrations. Calibration for PB was linear in the range of 0-50 microg/ml. The coefficients of variation were 3.4-5.0% and 5.9-7.5% in the within-day and between-day assays, respectively. The extraction recovery rates were 87.5-105.4%. By this method, it was possible to measure plasma PB concentrations in rat offspring without killing. These results suggested that this method is very useful to determine the plasma PB concentration derived from mothers milk in newborn rats.

Medication Instruction for Child Patients with Epilepsy. (IV). Survey of Patient Consideration after Leaves Hospital.

We conducted an anonymous questionnaire mail survey on patients, who had received medication instructions while hospitalized and were later discharged from the Department of Child Neurology from the first of October 1993 to the end of November 1995. The average age of the patients was 5.4 (0-21) years old, and the average frequency of medication instruction was 8.4 (1-46) times. The results of the overall evaluation from patients and/or their family to the medication instruction was “It was good” ; 92.3%, “Can not judge” ; 6.6%, and “It was bad” ; 1.1%, Moreover, it was “Necessary” ; 93.4%, “Not necessary” ; 1.1%, and “Can not judge” ; 5.5%. Regarding the question “Were the medication instructions sufficient?” “It was good” was 92.3% as an overall evaluation. Therefore, the medication instructions were generally considered to be good by the patients and/or their family. The results obtained from this survey were thus valuable in evaluating the medication instructions for child epilepsy patients.

Medication Instructions for Child Patients with Epilepsy (III) : Prescription Analysis of the Dosage Form for Valproic Acid

Various dosage forms of valproic acid (VPA) prescribed for 53 child patients with epilepsy were analyzed. These patients were all given medication instructions during hospitalization at the department of Child Neurology for 21 months from 1 October 1993 to the end of June 1995. Patients less than 1 year old, who were treated with VPA, represented the largest group in our study. The prescription frequency of syrup, fine granules, long-active granules, tablets and longactive tablets in VPA dosage forms was 39, 23, 15, 15 and 8%, respectively. The selection of dosage form changed from liquid form to the powder and then to the tablet as the patient age increased. These results suggest that various dosage forms of antiepileptics such as VPA contribute to not only the pharmacotherapy of such child patients with epilepsy but also to an improvement in their quality of life.

Changes in Serum Level of Four Antiepileptics in Okayama University Hospital over 14 Years.

Changes in the serum level of four antiepileptics (phenytoin, phenobarbital, carbamazepine, and valproic acid), which were measured by Okayama University Medical School Hospital, were surveyed for 14 years from 1981. The distribution of phenytoin concentrations in serum shifted from a low-concentration area to a wide-ranging area. The phenobarbital concentrations were distributed from wide-ranging area to a low-concentration area and recently again to a wide-ranging area. The distribution of carbamazepine concentration changed from a low-concentration area to a middle-ranging area. The distribution of valproic acid concentration altered from a low-concentration area to a wide-ranging area containing a very high-concentration area. In analyzing the distribution of each drug concerning its effective therapeutic concentration, phenytoin and phenobarbital presented low ratios, whereas the ratios of valproic acid and carbamazepine were very high. These results suggest that the direction of the serum level of these four measured antiepileptic drugs differed. They also suggested that serum level monitoring of antiepileptic drug is useful for administering the drug therapy of epileptic patients.