Search PubMed⌕ Search

Biomedical subjects

O Takaiti

Publications and source records attributed to O Takaiti.

30 records · Page 2Linked to original sources
PubMed1989

Metabolic fate of the new anti-ulcer drug enprostil in animals. 2nd communication: whole-body autoradiographic distribution of [3H]-enprostil in rats.

The distribution of radioactivity was studied by whole-body autoradiography in rats after oral or intravenous administration of [3H]-enprostil ((+/-)-11a-15a-dihydroxy-9-oxo-16-phenoxy-17,18,19,20-tetranorp r osta-4,5,13(t)- trienoic acid methyl ester, TA-84135) at a dose of 23 micrograms/kg. After oral administration to male rats, radioactivity in almost all the tissues and organs reached a peak within 15 min to 1 h. The highest levels of radioactivity were found in the contents of the stomach and intestine. High levels of radioactivity were also observed in the liver and kidney, and moderate levels were found in the lung, blood, dental pulp and the walls of the stomach. Radioactivity was the lowest in the skeletal muscle, testis, eye and brain. After reaching peak levels, radioactivity in the body decreased gradually, and it was detected only in the excretory organs at 24 h after drug administration. The distribution pattern after the intravenous dose was essentially similar to that after oral administration. The distribution profile of radioactivity in non-pregnant female rats after an oral dose was similar to that in male rats. Placental transfer and excretion in milk of radioactivity was slight. When the affinity of this compound to the melanin-containing tissues such as the uveal tract of the eye and the hair follicle was examined using pigmented rats, no tendency to retention of radioactivity in these tissues was observed.

Administration, Oral↗
PubMed1989

Metabolic fate of the new anti-ulcer drug enprostil in animals. 3rd communication: tissue accumulation after consecutive oral administration of [3H]-enprostil in rats.

Accumulation characteristics of radioactivity in organs and tissues were investigated after oral administration of [3H]-enprostil ((+/-)-11a,15a-dihydroxy-9-oxo-16-phenoxy-17,18,19,20-tetranorp r osta-4,5,13(t)- trienoic acid methyl ester, TA-84135) to male rats once a day (20 micrograms/kg/d) for 1, 7 or 14 days. [3H]-Enprostil was found to be partially metabolized in vivo to volatile tritium (3H2O). The ratios of volatile tritium to total radioactivity in plasma increased with repeated administration of [3H]-enprostil and the levels of volatile tritium were almost equilibrated within 7 days of drug administration. The formation rate of volatile tritium was estimated to be 1-2% of the single dose. The blood levels of non-volatile radioactivity at 1 h after each daily dosing were nearly constant. The levels at 24 h, however, increased with repeated dosing. The levels of non-volatile radioactivity in most tissues at 1 h after the multiple administration (7 and 14 times) were higher than those after the single dose. At 24 h, levels were noticeable after multiple dosing even in the tissues in which levels below the detection limit were found after the single dose. From the comparison of the multiple-dose groups, the levels in most tissues attained steady state within 7 times dosing. The daily excretions of radioactivity in the urine, feces and expired air were constant throughout the period of consecutive administration. The total recovery of administered dose was 92%, which was similar to that achieved in the single-dosing group. As described above, the retention of non-volatile radioactivity was observed in most tissues.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1989

Metabolic fate of the new anti-ulcer drug enprostil in animals. 4th communication: effect on hepatic drug metabolizing enzyme system in rats.

Effects of multiple oral administration of enprostil ((+/-)-11 alpha,15 alpha-dihydroxy-9-oxo-16-phenoxy-17,18,19,20-tetranorprosta- 4,5,13(t)-trienoic acid methyl ester, TA 84135) (20 micrograms/kg/d) and its solvent propylene carbonate (PC, 100 microliters/kg/d) on body weight gain, liver weight, hepatic drug metabolizing enzyme system and hexobarbital sleeping time were investigated in male rats during a 14-day period. Cytochrome P-450 content (as compared to the untreated control) and cytochrome b5 content (as compared to PC treated group) were slightly, but significantly, reduced in the group given a single oral dose of enprostil. However, these slight reductions were not augmented significantly by repeated administrations of enprostil. Slight but significant increase in microsomal protein content was observed in the group given 14 oral doses of enprostil and PC. Enprostil did not affect the other indicators used to evaluate the status of the hepatic drug metabolizing enzyme system. Additionally, single or multiple oral doses of enprostil or PC showed no effect on the hexobarbital-induced sleeping time. It therefore may be safely concluded that multiple oral administration, both of enprostil and of PC, has very little effect on drug metabolizing enzyme inducing or inhibiting activity in rats.

Animals↗
PubMed1989

Metabolic fate of the new Ca++-channel blocking agent (+)-(2S,3S)-3-acetoxy-8-chloro-(2-(dimethylamino)ethyl)-2,3-dihydro- 2-(4-methoxyphenyl)-2,5-benzothiazepin-4-(5H)-one maleate. Distribution, excretion and protein binding in rats and dogs.

Distribution, excretion and protein binding of (+)-(2S,3S)-3-acetoxy-8-chloro-(2-(dimethylamino)ethyl)-2,3-dihydro- 2-(4-methoxyphenyl)-2,5-benzothiazepin-4-(5H)-one maleate (TA-3090) in rats and dogs were investigated after oral (30 mg/kg (rats), 2 mg/kg(dogs] and intravenous (3 mg/kg (rats), 0.2 mg/kg (dogs) administration of 14C-TA-3090. Plasma level of radioactivity in rats reached plateau (6.04 micrograms equiv. of TA-3090 free base/ml) 1 h after oral administration. The plateau level continued at least up to 6 h. The plasma concentration of the unchanged drug (free base) reached the maximum (425 ng/ml) at 45 min after oral administration, and then decreased with a half-life of 1.16 h. Plasma level of radioactivity after intravenous administration to rats rose gradually up to 1 h and thereafter it was kept constant for 6 h. Plasma concentration of the unchanged drug decreased with half-lives of 0.43 h (alpha phase) and 1.33 h (beta phase) after intravenous administration. In dogs, the peak level of plasma radioactivity after oral administration was 227 ng/ml at 1 h. The Cmax, Tmax and t1/2 of unchanged drug were 31 ng/ml, 1.34 h and 4.13 h, respectively. The plasma levels of total radioactivity and unchanged drug after intravenous administration to dogs were 146 and 142 ng/ml at 1 min, respectively. The t1/2 of the plasma radioactivity were 0.02 h (alpha) and 4.02 h (beta). Those of unchanged drug were 0.03 h (alpha) and 1.66 h (beta).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1983

Effect of trimebutine maleate on bethanechol-induced contractions of gastrointestinal tract in conscious and anaesthetized dogs.

The effect of trimebutine maleate (TM-906) on bethanechol-induced contractions of the gastrointestinal tract in dogs was studied by means of chronically implanted force transducers, and it was compared with that of metoclopramide and atropine. During the period of motor quiescence in the fasted state of conscious dog, a bolus i.v. injection of 10 to 50 micrograms/kg bethanechol caused rhythmic contractions in the stomach and small intestine, in which an increase in basal tone was often accompanied in the distal ileum. The stomach responded to a less extent than the small intestine. Intravenous infusion of TM-906 at 3.0 mg/kg-hr for 20 to 60 min reduced the gastric contractions induced by 20 to 30 micrograms/kg bethanechol in five out of six conscious animals examined. The drug, however, enhanced the contractions of the duodenum and jejunum in a majority of the animals. Metoclopramide (1.8 mg/kg-hr) showed a tendency to potentiate the bethanechol-induced contractions in the stomach and small intestine, and atropine (0.06 mg/kg-hr) diminished them. In pentobarbital-Na anaesthetized dogs, effects of TM-906 on bethanechol-induced contractions resembled those in conscious dogs, inhibition in the stomach and potentiation in the small intestine.

Animals↗
PubMed1982

[Effects of trimebutine maleate on interdigestive motility of the stomach and small intestine in conscious dogs].

Effects of trimebutine maleate (TM-906) on gastrointestinal motor activity of interdigestive state were studied in seven unanaesthetized dogs by means of chronically implanted force transducers. In animals which showed typical interdigestive motor pattern consisted of long lasting motor quiescence and recurring high-amplitude contractions (interdigestive contractions), intravenous infusion of TM-906 (0.6-6.0 mg/kg-hr) shortened the quiescent period. During TM-906 infusion, the number and the duration of the interdigestive contractions decreased in the gastric antrum. These effects were in a dose dependent manner. Infusion of TM-906 of 6.0 mg/kg-hr over 60 min introduced additional responses: persistent contractions different from the usual interdigestive contractions and delayed onset of the interdigestive contractions. Metoclopramide (1.8-6.0 mg/kg-hr) developed high-frequency contractions with gradually increasing amplitude and caused enhancement of the interdigestive contractions. In three animals which showed anomalous fasted motor pattern consisted of continuous low-amplitude contractions, bolus i.v. injection of TM-906 (2.0-2.5 mg/kg) introduced a transient suppression of the contractions in the antrum. Metoclopramide (1.0 mg/kg i.v.) potentiated and hyoscine-N-butylbromide (0.1 mg/kg i.v.) inhibited the contractions in all the regions.

Animals↗
PubMed1974

M-protein.

Explore the source record for details and available documents.

Amino Acids↗
PubMedDate not supplied

First pass metabolism and in vitro metabolism of a new orally active dopamine prodrug, N-(N-acetyl-L-methionyl)-O,O-bis(ethoxycarbonyl)dopamine in dogs.

To elucidate the first pass metabolism of the dopamine prodrug N-(N-acetyl-L-methionyl)-O,O-bis(ethoxycarbonyl)dopamine (TA-870) in the small intestine and liver of dogs, the blood and plasma concentrations of unchanged TA-870 and metabolites in the gastroduodenal vein, portal vein, hepatic vein, and abdominal aorta were measured by HPLC after intraduodenal administration of TA-870. In addition, an in vitro metabolic study of TA-870 was carried out using liver, small intestinal wall, and blood homogenates of dogs. The order of maximal concentration (Cmax 0-30 min) in gastroduodenal blood or plasma was unchanged TA-870 greater than deethoxycarbonylated TA-870 (DEC-TA-870) greater than conjugated dopamine greater than free dopamine (DA) greater than free homovanillic acid (HVA) greater than free 3,4-dihydroxyphenylacetic acid (DOPAC). This result showed that the main pathway of metabolism in the small intestine is catechol ester hydrolysis and minor pathways are amido hydrolysis, oxidative deamination, and catechol 3-O-methylation. The order of Cmax in the hepatic vein and abdominal aorta was conjugated DA greater than free DEC-TA-870 greater than free HVA greater than free DA greater than free DOPAC greater than conjugated DOPAC greater than unchanged TA-870. The main metabolic pathways in the liver were hydrolyses of ester and amido-linkage of TA-870 and conjugation of DA. In the in vitro studies, the main metabolites of TA-870 in liver, small intestinal wall, and blood homogenates were DEC-TA-870, 3- or 4-mono-deethoxycarbonylated TA-870, DA, and an unknown compound.(ABSTRACT TRUNCATED AT 250 WORDS)

3,4-Dihydroxyphenylacetic Acid↗
PubMedDate not supplied

Disposition of a new orally active dopamine prodrug, N-(N-acetyl-L-methionyl)-O,O-bis(ethoxycarbonyl) dopamine (TA-870) in humans.

Dopamine (DA) levels in human plasma after oral administration of TA-870 and iv infusion of DA were measured by HPLC. The metabolites of TA-870 or DA in plasma and urine were also determined. The maximal concentrations (Cmax) of free DA in plasma after oral administration of 750 and 1500 mg of TA-870 to humans were 63 and 127 ng/ml, respectively, being higher than the concentrations of 8 and 31 ng/ml following the infusion of 1 and 3 micrograms/kg/min, the clinical doses of DA. These results demonstrated the clinical usefulness of TA-870. The plasma level of free deethoxycarbonylated TA-870 (DEC-TA-870) after oral administration of TA-870 was higher than that of DA. After oral administration of TA-870, the concentration of 3,4-dihydroxyphenylacetic acid (DOPAC) in plasma was higher than that after DA infusion, but the concentration of homovanillic acid (HVA) was about the same as that after DA infusion. The level of the total urinary metabolites (free and conjugated) after oral administration of TA-870 decreased as follows: DA greater than HVA greater than DOPAC greater than DEC-TA-870. The conjugated/free ratios of urinary metabolites after TA-870 dosing were 40-66 for DA, 0.5 for HVA, 0.6-0.9 for DOPAC, and 5.0-6.2 for DEC-TA-870. The composition of urinary metabolites after oral dosing of TA-870 was almost the same as that the DA metabolites. These results show that TA-870 is rapidly converted to DA in the human body.

3,4-Dihydroxyphenylacetic Acid↗