Yasunori Araki

Phenobarbital in Sera of Epileptic Mothers and Their Infants.

The phenobarbital (PB) transition from epiletpic mothers to their breast milks and offspring in cases of PB monopharmacy with other antiepileptic drugs was investigated in 26 epileptic mothers and 24 offspring who were taking the breast milk from epileptic mothers. The mothers serum PB concentration in monopharmacy was almost the same in various stages (stage I, with 5 days after the delivery; stage II, 6–10 days after; stage III, 1–2 months after; stage IV, 3–5 months after). However, the PB concentrations in polypharmacy were markedly higher than those in monopharmacy. Concerning the PB concentration in breast milk, a significant increase was found in polypharmcy in comparison with monopharmacy only in stage I. On the other hand, the offsprings PB concentration in polypharmacy was markedly higher than that in monopharmacy, particulary in stage I. In another stages, PB concentration in monopharmacy gradually decreased according to the increase of stages. These results indicate that pharmacokinetics of antiepileptic drugs in the perinatal may be considerably different in PB monopharmacy and polypharmacy.

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.

Effect of bilateral septal lesions on discrimination avoidance conditioning in rats

Studies were performed, using the two-way shuttle box method, on the acquisition of discrimination avoidance by rats with bilateral lesions of the septum (septal rats) in relation to changes in emotional behavior. Septal rats exhibited hyperreactivity immediately after the lesions were made: their startle, struggle and vocalization responses to stimuli were markedly increased. These hyperemotional responses, however, decreased and returned to the normal level 7 days after surgery. Initially, the septal rats showed elevated conditioned avoidance responses to both the CS+ and the CS-. In later stages, their responses to the CS+ showed progressive and gradual increase, accompanied by a decrease in responses to the CS-, until responses to both stimuli were only slightly elevated above the level of control rats. These results suggest that bilateral lesions of the septum do not affect discrimination ability itself. The impairment of discrimination avoidance during the initial stages may result from the transient impairment of the discrimination acquisition process.

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.

Effect of Quinone Derivatives on Ethanol and Acetaldehyde Metabolism in Rats

Quinone derivatives, such as 2, 3-dimethoxy-5-methy1-6-decapreny1-1, 4-benzoquinone (ubidecarenone, coenzyme Q10, CoQ10), 4, 5-dihydro-4, 5-dioxo-1H-pyrrolo [2, 3-f] quinoline-2, 7, 9-tricarboxylic acid (pyrroloquinoline quinone, PQQ) and 6-(10-hydroxydecy1)-2, 3-dimethoxy-5-methy1-1, 4-benzoquinone (idebenone), significantly inhibited rise of acetaldehyde concentration in blood and liver of rats following ethanol ingestion.Acetaldehyde concentrations decreased in vitro with incubation with 1, 4-benzoquinone or PQQ solution at 40°C. Low acetaldehyde concentrations following ethanol ingestion might be due to PQQ-accelerated oxidation of acetaldehyde.

Effect of acute treatment of mice with L-histidine on the brain levels of amino acids.

The brain histidine level in mice dose-dependently increased 1 and 2 hr after an i.p. injection of 0.5-1.5 g/kg of L-histidine. The treatment with 1.0 and 1.5 g/kg but not 0.5 g/kg of L-histidine significantly decreased the brain levels of tyrosine, phenylalanine and some other amino acids 1 hr later. A complete recovery or a rebound rise of amino acid levels was observed 2 hr after treatment. These results indicate that there is a change in the transport of amino acids into the brain after treatment with large doses of L-histidine.