Plasma concentration, distribution, and excretion of 14C-alendronate after a single intravenous administration were investigated in 7-week old male rats. 1. The plasma levels of radioactivity after ...administration of 0.05, 0.5, 5 and 15 mg/kg of 14C-alendronate declined rapidly with time at each administered dose. The elimination half-lives were 3-10 minutes (from 5 to 30 min) and 27-60 minutes (from 30 min to 2 hr), and no significant difference in the half-lives was observed between the doses. 2. The level of radioactivity in bones and cartilage after administration of 0.05 mg/kg of 14C-alendronate was higher than in plasma and noncalcified tissues at any time points measured after dosing. The concentration in vertebra was the highest among bones, followed by long bones (femur, tibia, humerus) and calvaria. The autoradiography of the long bones revealed a higher level of radioactivity was observed in metaphysis and epiphysis than in diaphysis, especially in the area adjacent to growth plate. Therefore, it was suggested that alendronate was distributed well to region of bone with high turnover. 3. The radioactivity in bones reached a peak concentration at approximately 8 hours after administration and then decreased with a half-life of between 65 and 102 days. Moreover, the half-life of the contents of radioactivity in the long bones and vertebra was between 182 and 242 days. This suggested that decrease in the level of radioactivity in bones was mainly due to increase in bone weight with growth, and substantial elimination of the drug was slow in bones. The uptake of alendronate by bones increased in a dose dependent manner in the range of 0.0515 mg/kg. 4. The radioactivity in noncalcified tissues was lower than in bones, and its decrease was rapid. 5. By the 9th day after administration of 14C-alendronate at 0.05 mg/kg, 37.5% of the dosed radioactivity was excreted in the urine and 0.3% in the feces. Most of the radioactivity in the urine was excreted within 12 hours after administration.
Biotransformation of 3-p-trans-4-aminomethyl-cyclohexylcarbonyl)phenylpropionic acid hydrochloride (TEI-5103) was studied in rats and dogs. 1) Three metabolites which were related chemically to ...TEI-5103 were detected in urine; they were identified on a UV spectrum, Chromatograph and Mass spectrum by direct comparison with authentic compounds as follows: 3-p-(4-carboxycyclohexylcarbonyl)phenylpropionic acid (M-1), p-(4-carboxycyclohexylcarbonyl)benzoic acid (M-2), p-(4-carboxycyclohexylhydroxymethyl)benzoic acid (M-3). Metabolite M-3 was detected only in dogs. 2) In rat plasma, the major metabolites were M-2, unchanged drug and M-1; while in dogs, unchanged drug, M-3 and M-1. 3) After oral and intravenous administration, M-2, unchanged drug and M-1 were mainly excreted to the urine in rats while in dogs, M-3, M-2 and unchanged drug were the main metabolites excreted to the urine. 4) M-2 was mainly excreted with bile in rats. In dogs, M-2 and M-1 were a major metabolites excreted to feces after intravenous administration.
The absorption and excretion of 14C-TEI-5103 after single oral (200 mg/kg) or intravenous (10 mg/kg) administration were studied in rats and dogs. 1. After oral administration of 14C-TEI-5103, the ...amount absorbed from the gastrointestinal tract was estimated as about 3 % in rats and about 6 % in dogs. 2. After oral administration, the maximum concentration of radioactivity was obtained at 0.5 hr in rats and 1 hr in dogs, and was followed by a biexponential decline with initial biological half-lives (T1/2) of 0.6 hr in rats and 1.5 hr in dogs. After intravenous administration, the elimination of radioactivity from plasma in both species was rapid and biphasic. 3. After oral administration in rats, 1.6 % of the dose was excreted in the urine and 100.1 % of the dose in the feces, within 72 hr. In dogs, 3.9 % and 94.9 % of the dose was excreted with urine and feces respectively. In both species, most of radioactivity was excreted with urine and feces within 24 hr. 4. The cumulative excretion of radioactivity into bile amounted to 2.8 % and 42.7 % of the dose within 24 hr after oral and intravenous administration, respectively. 5. Protein binding of 14C-TEI-5103 in vitro was 44-45 % in rat plasma, and 21-23 % in dog plasma. In vivo, plasma protein binding was about 64 % at 0.5 hr after oral administration of 14C-TEI-5103 to rats.
Plasma concentration, distribution, and excretion of 14C-alendronate were investigated after repeated intravenous administration once a day for 7 days to 7-week old male rats and after a single ...intravenous administration to 30-week old male rats. Feto-placental transfer in pregnant rats and the transfer into the milk in lactating rats were also investigated. 1. The plasma radioactivity after repeated administration at 0.05 mg/kg of 14C-alendronate to 7-week old male rats was higher than in single administration. However, there was no difference in the half-lives. The level of radioactivity in noncalcified tissues after repeated administration were also higher than in a single administration, but no accumulation was observed. The maximum level of radioactivity in bones was 6.2-7.5 times higher than in a single dose experiment. The concentration in vertebra was the highest among bones, followed by long bones (femur, tibia, humerus) and calvaria. By the 24th day after final administration, 32.2% of the dosed radioactivity was excreted in the urine and 2.1% in the feces, and the excretion in urine was almost completed within 24 hours. These results suggest that there is no alteration in the disposition of alendronate after repeated administration compared with single administration. 2. The AUC of plasma radioactivity after single administration of 0.05 mg/kg of 14C-alendronate to 30-week old male rats was 2 times higher than in 7-week old rats. The radioactivity in the liver, kidneys, spleen, and heart was also higher. The maximum level of radioactivity in calvaria in 30-week old rats were similar to those in 7-week rats, but was approximately 50% lower in vertebra and long bones than in 7-week old rats. Therefore, the difference of concentration among bones in 30-week old rats was less than in 7-week old rats. The cumulative urinary excretion at 216 hours after administration to 30-week rats was higher (46% of dose) than in 7-week old rats. On the basis of these results, it is suggested that the increase of concentration of radioactivity in plasma and noncalcified tissues and urinary excretion in 30-week rats is due to the decrease in the bone uptake of alendronate as a consequence of decline of bone turnover. 3. After single administration of 14C-alendronate at 0.05 mg/kg to female rats on day 19 of pregnancy, the concentration of radioactivity in plasma was similar to that of 7-week old male rats. Radioactivity was not detected in fetus, indicating that feto-placental transfer of alendronate was low. 4. After administration of 14C-alendronate to female rats 14 days post parturn, the concentration of radioactivity in the milk was higher than in plasma. The transfer of radioactivity into milk was observed.
In recent years, Liquid Crystal Display(LCD) panels have been developed as light valves for projectors. This paper describes an outline of the signal processing for WS-LCDPJ, which has been ...developed, using three 4.2-inch a-Si TFT-LCDs with 1,280×1,024 pixels.
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