Kohei Eto

Simple and sensitive assay of zonisamide in human serum by high-performance liquid chromatography using a solid-phase extraction technique

A rapid and sensitive method for the assay of zonisamide in serum was developed using a solid-phase extraction technique followed by high-performance liquid chromatography. A 20-microliter volume of human serum was first purified with a Bond-Elut cartridge column. Then, the methanol eluate was injected onto a reversed-phase HPLC column with a UV detector. The mobile phase was acetonitrile-methanol-distilled water (17:20:63, v/v) and the detection wavelength was 246 nm. The detection limit was 0.1 micrograms/ml in serum. The coefficients of variation were 4.2-5.6% and 5.1-9.1% for the within-day and between-day assays, respectively. This method can be used for clinical pharmacokinetic studies of zonisamide in serum even in infant patients with epilepsy.

Effect of chlordane on hepatic mitochondrial respiration

In order to clarify the cytotoxicity of chlordane, an industrial product used as an insecticide, its effect on oxidative phosphorylation in rat hepatic mitochondria was studied. The respiration rate, RCI and ADP/O ratios were inhibited by chlordane-related compounds; the degree of inhibition was in the descending order of trans-chlordane, cis-chlordane, heptachlor and heptachlorepoxide. Of the indices indicating various respiratory activities, state 3 respiration was the most sensitively inhibited by these compounds, suggesting that they inhibit energy transfer. However, electron transport was inhibited also by high concentrations of chlordane constituents. The inhibitory effect of the chlordane constituents on respiratory activity varied depending on the species of respiratory substrate, suggesting site-specificity of these compounds. The release of K+ ions paralleled the results of the respiratory activity study. Heptachlorepoxide, a metabolic product of heptachlor, had less effect on mitochondria than heptachlor.

Effect of Cigarette Smoking on Theophylline Pharmacokinetics in Rats

Abstract— The effect of acute cigarette smoke inhalation on the plasma levels of theophylline administered orally and parenterally to rats has been studied. The animals were exposed to smoke containing low‐ or high‐nicotine/tar concentration for 10 min immediately after oral, intraperitoneal (i.p.) or intravenous (i.v.) administration of theophylline. The plasma levels of theophylline when administered orally (20 mg kg−1) were lower in the two cigarette smoke‐inhaling groups than in the non‐smoking restrained control group, with the lowest values in the high‐nicotine/tar group. The plasma levels (8 and 12 h after administration) in the high‐nicotine/tar group when theophylline was administered i.p. (10 mg kg−1), were also slightly lower than in the non‐smoking restrained control group but this was not significant. When theophylline was administered i.v. (5 mg kg−1), there was no difference between the high‐nicotine/tar group and the nonsmoking restrained control group. These data indicate that cigarette smoke inhalation causes suppression or delay of theophylline absorption from the gastrointestinal tract.

Microdetermination of cimetidine in rat plasma by high-performance liquid chromatography

Abstract A rapid and simple method for the microdetermination of cimetidine in plasma from a single animal was investigated using high-performance liquid chromatography (HPLC). A microquantity (20 μl) of plasma from the rat tail vein was used without solvent extraction, and pharmacokinetic studies did not require the sacrifice of many animals. The recovery of added cimetidine averaged 97%. Coefficients of within-day variation ranged between 2.6 and 8.6%. The coefficient of correlation for the calibration curve in the concentration range of 0 to 10.0 μg/ml was 0.998. The detection limit was 0.1 μg/ml in the plasma. An excellent correlation was found between the concentration of cimetidine in the tail vein and that in the inferior vena cava. In addition, the plasma cimetidine concentration-time data for small animals could be obtained by this method.

Influences of Immobilization and Footshock Stress on Pharmacokinetics of Theophylline and Caffeine in Rats

The influences of immobilization and footshock stress on pharmacokinetics of theophylline (20 mg kg−1) and caffeine (30 mg kg−1) administered orally were examined in rats.

Influences of long-term cigarette smoke exposure on pharmacokinetics of theophylline, and on liver microsomal enzymes in rats.

The influences of long-term cigarette smoke exposure on pharmacokinetics of oral theophylline (20 mg/kg), and on liver microsomal enzymes which metabolize drugs were studied in rats. Animals were exposed to cigarette smoke for 20 min each in the morning and evening every day for 26 days in the pharmacokinetic study, and 27 days for the enzyme assays. Theophylline was administered 13 h after the last exposure to smoke, and plasma concentrations were measured using HPLC. Plasma concentrations of theophylline during the absorption phase and 6 h after oral administration were lower in the long-term cigarette smoke-exposed group than in the control group. In the smoke-exposed group, the AUC and Ka were lower, and the Ke was slightly higher than in the control group. Liver weight and the ratio of liver weight to body weight were lower in the smoke-exposed group, and cytochrome b5 content and NADPH-cytochrome P-450 reductase activity were higher, but cytochrome P-450 content did not differ from the control group. These results indicate that long-term exposure to cigarette smoke suppresses theophylline absorption from the gastrointestinal tract, accelerates its elimination, and affects liver microsomal enzymes which metabolize drugs.

Influences of cigarette smoke inhalation on pharmacokinetics of cimetidine in rats.

The influences of cigarette smoke inhalation on the pharmacokinetics of cimetidine administered orally and parenterally were investigated in rats using a smoking machine. The animals were exposed to two kinds of cigarette smoke, low- or high-nicotine.tar, inhaled for 10 min immediately after oral (50 mg/kg), intraperitoneal (25 mg/kg) or intravenous (10 mg/kg) administration of cimetidine. The plasma level after cimetidine was administered orally was lower in the absorption phase in the two cigarette smoke inhaling groups than in the non-smoking control group, and was particularly marked in the high-nicotine.tar cigarette smoke inhaling group. In contrast, no significant difference was found in cimetidine plasma level between the cigarette smoke inhaling groups and the non-smoking control group when administered intraperitoneally or intravenously. These results suggest that cigarette smoke inhalation may cause a suppression or a delay in cimetidine absorption from the gastrointestinal tract, and that the degree of influence is dependent upon the content of nicotine.tar in the cigarette smoke.