[Evaluation of dissolution behavior for the products containing tegafur and uracil].

Generic drugs are widely used with the object of cost saving in many Japanese therapeutic scenes now. The products containing the same active ingredient(s), even if they are innovative drugs or generic ones, must be designed to possess the equivalent quality. In this report, we observed the dissolution behavior patterns of three generic drugs that contain Tegafur and Uracil, drugs A, B, and C, and compared them with that of an innovative product, UFT. Drugs B and C were similar to UFT in the dissolution rate of Tegafur, but drug A was not. On the dissolution rate of Uracil, all the generic products, drugs A, B and C, did not amount to the level equivalent to that of UFT. Therefore, these generic products did not indicate the same dissolution behavior pattern as UFT. It was suggested that the pharmaceutical technology used in the manufacture was not equivalent even if the products of the same dosage form contain the same kind and content of the active ingredient(s).

Endothelin-1 stimulates sodium-dependent calcium efflux from bovine adrenal chromaffin cells in culture.

1. The effect of endothelin (ET)-1 on Ca2+ efflux from cultured bovine adrenal chromaffin cells was examined. ET-1 (10(-7) M) significantly increased intracellular free Ca2+ level ([Ca2+]i), 45Ca2+ uptake and catecholamine secretion in the cells. 2. ET-1 stimulated the efflux of 45Ca2+ from the cells preloaded with 45Ca2+ in a concentration-dependent manner (10(-9)-10(-7) M). This stimulatory effect was inhibited by ET(B) receptor antagonist BQ788, but not by ET(A) receptor antagonist BQ123. Selective ET(B) receptor agonists Suc-[Glu9, Ala11.5]-ET-1 and sarafotoxin S6c (SRTX) also stimulated 45Ca2+ efflux from the cells. 3. ET-1, Suc-[Glu9 Ala11.15]-ET-1 and SRTX increased the level of cyclic GMP in the adrenal chromaffin cells. ET-1 induced an increase in the nitric oxide (NO) level in the cells. The stimulatory effects by which ET- increases NO level and 45Ca2+ efflux were inhibited by NG-monomethyl-L-arginine acetate (L-NMMA), a competitive inhibitor of NO synthase. 4. The 45Ca2+ efflux stimulated by ET-1 was inhibited by deprivation of extracellular Na+, but not by deprivation of Ca2+. 5. These results suggest that ET-1 stimulates an extracellular Na+-dependent Ca2+ efflux through the activation of NO synthase in cultured bovine adrenal chromaffin cells.

Electroencephalographical analysis of acute paraquat poisoning.

The disturbances in the central nervous system of rabbits induced by gramoxon poisoning were studied by examination of subcortical electroencephalograms (EEGs) and power spectral analysis of EEGs. The following results were obtained. Administration of the fatal gramoxon (2.0 ml/kg i.p.) resulted in increases of slow frequency discharges from the reticular formation (RF), and from the hippocampus (Hpc) and sensorimotor cortex (Cm) after about 5 minutes and 20 minutes, respectively, detected by power-spectrum array. After about 30 to 40 minutes, the discharges from the Cm changed to rapid frequency discharges. The discharges from the Hpc and Cm decreased after about 50 to 60 minutes, and increased again in the agonal stage, and then seizure discharges developed. Soon after administration of gramoxon solution, the heart rate and respiratory rate increased and the PCO2, base excess (BE) and [HCO3-] decreased transiently. These findings indicate a shift to acute respiratory alkalosis and thereafter a shift to metabolic acidosis. Subsequently, the blood pressure, heart rate, respiratory rate, pH, BE and [HCO3-] decreased and the PCO2 increased. These findings indicate a shift to respiratory and metabolic acidosis. After about 70 minutes, the EEGs from all leads became almost flat, respiration ceased, and the blood pressure decreased to zero. After administration of gramoxon solution, the paraquat concentration in the blood increased rapidly. These results suggest that rapid increase in the paraquat concentration in the blood after gramoxon administration affects the central nervous system from an early stage.

Electroencephalographical analysis of acute drug intoxication--SS Bron solution-W.

Disturbances of the central nervous system due to abuse of SS Bron solution-W (B-solution), an antitussive and expectorant containing dihydrocodeine and other constituents, were studied in rabbits. Animals were given 20 ml/kg of B-solution orally at 4 hour intervals for 8 hours or more, and changes in the electroencephalograms (EEGs) from the reticular formation(RF), hippocampus(Hpc) and sensorimotor cortex(Cm) were examined. The following results were obtained. About 3 hours after administration of B-solution, the EEG from the Hpc showed low voltage, slow wave, the heart rate decreased rapidly, and the respiratory rate increased. After about 7 to 7.5 hours, the EEG from the Cm showed slow wave hypersynchrony and stimulation of the RF with square pulses of 2.0 V induced slight arousal reactions in the Cm and Hpc. The blood pressure and respiratory rate decreased, and ECG changes indicated atrial flutter-fibrillation and ventricular tachycardia. Power-spectrum array analysis indicated increase of slow frequency discharges in the EEGs from all regions. The slow wave hypersynchrony of the EEG from the Cm and slow wave, low voltage of the EEG from the Hpc seemed to be associated with hallucination and delusion.