Yoshihiro Shirakawa

Effect of ipriflavone on glucocorticoid-induced osteoporosis in rats.

Ipriflavone, 7-isopropoxy-3-phenyl-4H-1-benzopyran-4-one, was administered orally for 12 weeks to male rats with prednisolone-induced osteoporosis. Microdensitometric analysis of a roentgenograph of the femurs revealed that ipriflavone increased the density of the distal metaphysis dose-dependently and tended to increase the density of the diaphysis. It also inhibited dose-dependently the decrease in the mechanical strength of the tibia, breaking strain and breaking energy, and the fractional content of ash in femurs. These results indicate that ipriflavone markedly suppresses bone resorption at the metaphysis where the content of trabecular bone with a rapid turnover rate is high, and possibly inhibits bone reduction at the diaphysis.

Metabolism of 8-Chloro-6-phenyl-4H-s-triazolo[4,3-α][1,4]-benzodiazepine (D–40TA), a New Central Depressant. I. Absorption, Distribution and Excretion in Rats

1. [14C]D–40TA was quantitatively absorbed from the rat small intestine by the portal route.2. The blood level of oral D–-40TA reached a peak at 30 min and then declined with a half-life of 60 min. The level after intravenous injection fell off with a half-life of 32 min. D–40TA and its metabolites could enter erythrocytes. The drug was not bound to plasma protein.3. Oral administration of [14C]D–40TA caused a rapid and wide distribution of radioactivity in tissues, with the peak levels at 1 h. T this time, the radioactivity was highest in adrenal, followed by liver and skeletal muscle, and lowest in testis.4. D–40TA was detected in the brain 2 min after oral dosing. Brain levels of D–40TA were the same as, or slightly higher than the blood levels at all times, indicating that the drug easily passed through the blood–brain barrier. A pharmacologically active metabolite B also entered into the brain with ease.5. The oral drug was completely eliminated from the body within 3 days, 18% in urine and 82% in fa...

Metabolism of 8-Chloro-6-phenyl-4H-s-triazolo[4,3-a]-[1,4]benzodiazepine (D-40TA), a New Central Depressant. IV. Placental Transfer and Excretion in Milk in Rats

Abstract1. Placental transfer of [14C]D-40TA and [14C]nitrazepam was studied after intravenous injection to pregnant rats on the 14th and 20th days of gestation. In both stages of pregnancy, D-40TA and its 1-oxo metabolite freely crossed the placenta, their foetus/maternal blood concentration ratios 1 h after dosing being approximately 1. The corresponding ratios for nitrazepam were 0.3 in middle pregnancy and 0.7 in late pregnancy. Foetal levels of the two benzodiazepines were not significantly different, because of higher levels of nitrazepam in the maternal blood.2. Radioactivity concn. was at all times highest in placenta and foetus, and lowest in amniotic fluid, both in middle and late pregnancy. Radioactivity in these tissues disappeared as maternal blood levels declined.3. Autoradiography of rat foetuses in late pregnancy showed that, 1 h after injection of the mothers with the labelled compounds, relatively higher concns. were noted in the foetus adrenal, adipose tissue, liver and gastro-intestina...

The Metabolic Fate of α-Sulphobenzylpenicillin in Rats

1. After intramuscular injection of a new semi-synthetic penicillin, disodium [14C]α-sulphobenzylpenicillin, to rats radioactivity in blood reached a peak at 5 min with a half life of 26 min. Most of the blood radioactivity was not bound to plasma protein and 70% was accounted for as the intact penicillin.2. At 20 min after dosage the radioactivity was distributed mostly in liver, kidney, intestinal contents and blood. About half of the injected radioactivity was excreted into the urine within 8 h. Faecal excretion was much slower but continued for longer duration and amounted to 24% after 3 days.3. In bile-duct cannulated rats, 35% of the dosed radioactivity was excreted into bile and 52% into urine within 24 h.4. In both urine and bile, 50 to 85% of the radioactivity was present as unchanged drug and 10 to 20% as its penicilloic acid.5. Intravenous injection gave similar metabolic patterns as those observed after intramuscular injection except that faecal excretion was increased.6. Autoradiographic stud...

Metabolism of a Thyroxine Analogue, 3,5-Diiodo-4-(4′-acetoxy-3′-iodophenoxy)benzoic Acid in Rats

1. The metabolic fate of 3,5-diiodo-4-(4′-acetoxy-3′-[125I]iodophenoxy)-benzoic acid was studied in rats and its principal metabolites identified.2. The drug, orally administered, was rapidly and almost quantitatively absorbed from the intestine, and was distributed to liver and kidney. Blood levels of radioactivity reached a plateau 3 to 5 h after administration, and gradually decreased. Radioactivity was rapidly excreted, largely in the bile, and entered into entero-hepatic circulation. Subsequent excretion in faeces and urine, amounted to 60 and 25%, respectively, within 72 h.3. Repeated oral administration of the drug did not show any accumulation, except in the thyroid gland, which showed a concentration five times higher than that after a single administration.4. The metabolic fate of the drug in animals receiving a subtoxic dose of the unlabelled drug for 4 weeks did not significantly differ from that in control animals.5. The faecal metabolite was identified as the deacetylated drug. Glucuronide a...