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H Tone

Publications and source records attributed to H Tone.

69 records · Page 4Linked to original sources
PubMed1980

[Studies on the absorption, excretion and distribution of aclacinomycin A: absorption, excretion and distribution of 14C- or 3H-aclacinomycin A in mice, rats and rabbits (author's transl)].

A new anthracycline antitumor antibiotic, aclacinomycin A, was labeled with 3H uniformly or with 14C simultaneously at the anthracycline nucleus and L-rhodosamine. These labeled drugs were administered intravenously to normal dd mice, solid type Sarcoma 180 tumor-bearing ICR mice, normal or pregnant Wistar rats and normal rabbits, respectively. 14C-Aclacinomycin A given to rabbits (5 mg/kg) was rapidly cleared from the blood and transferred to tissues. But low level of radioactivity (equivalent to about 0.5 mcg/ml) was remained in the blood even 8 approximately 10 hours after administration. About 45% of the radioactivity were recovered from the urine and 20% from the feces by 72 hours after administration. Tissue levels of 3H-14C-aclacinomycin A given to normal and tumor-bearing mice were highest in the lungs and spleen. Higher distribution was observed also in the liver and kidneys 2 hours after administration. Bioassay revealed that the drug was present in the lungs and spleen in biologically active form and in the liver and kidneys in inactive form, respectively. In the tumor tissue the radioactivity was low but it persisted for 48 hours. Autoradiography with 14C-aclacinomycin A in rats demonstrated that radioactivity due to the drug distributed in the lungs, spleen, kidneys, thymus, intestine, lymph nodes, bone marrow, salivary gland, hypophysis and pineal body but it was rapidly cleared. About 0.2% of radioactivity given to a pregnant rat were transferred to a fetus when 14C-aclacinomycin A was administered intravenously on the 18 approximately 19th day of pregnancy.

Absorption↗
PubMed1980

[Studies on the absorption, excretion and distribution of aclacinomycin A: absorption, excretion and distribution of aclacinomycin A in mice, rabbits and dogs by photometric assay (author's transl)].

An anthracycline antitumor antibiotic, aclacinomycin A, was given to mice, rabbits or dogs intravenously to study the pharmacokinetics by photometric assay based on the absorption of anthracycline ring. The drug was rapidly eliminated from the blood in these animals. Drug levels were much higher in the blood cells than in the plasma. Tissue levels in dogs were 50 approximately 100 times higher than the blood levels, which showed the drug was rapidly transferred from the blood to tissues after administration. Higher levels were observed in the lungs, spleen and lymph nodes, where the drug was present as aclacinomycin A itself and the glycoside-type metabolites that were biologically active. The active form was also detected in the pancreas, heart, thymus, bone marrow and gastrointestinal tract. In the liver and kidneys, biologically inactive aglycone-type metabolites were observed. About 2 approximately 4% of the drug given to rabbits or dogs was recovered in the urine by 72 hours after administration, in which only 10% of the excreted drug was active form in rabbits but about 65% in dogs. The rest was inactive aglycone-type metabolites that were excreted almost in the conjugated form. Biliary excretion also contributed to the total clearance of the drug. Aclacinomycin A was absorbed even by oral administration in rabbits and dogs. Tissue distribution of the drug orally given to dogs was similar to that in intravenous administration, except that higher levels of active form were detected in the gastrointestinal tract and of inactive form in the liver.

Absorption↗
PubMed1980

[Cardiotoxic study of aclacinomycin A. Subacute cardiotoxicity of aclacinomycin A and its recovery in hamsters (author's transl)].

Male golden hamsters were treated with aclacinomycin A or adrianmycin by daily intraperitoneal injections for 15 consecutive days, and then allowed to be recovered for 15 days. Dose levels of aclacinomycin A and adriamycin were 1.5, 2.0 and 3.0 mg/kg, and 0.17 and 0.5 mg/kg, respectively. General toxicity, electrocardiogram (ECG), blood biochemical analysis and light microscopic and electron microscopic examinations were studied. The two drugs produced body weight loss at a dose of 3.0 mg/kg and 0.5 mg/kg, respectively. Death occurred in hamsters treated with aclacinomycin A at the highest dose (4/6 animals). In ECG study, aclacinomycin A-treated hamsters showed reversible QRS duration prolongation and T wave flattening at a dose of 1.5 or 2.0 mg/kg. Adriamycin-treated animals at a dose of 0.5 mg/kg showed R wave amplitude elevation during dosing period, and PR interval prolongation, R wave amplitude elevation and S wave amplitude reduction during recovery period. Blood biochemical analysis demonstrated reversible elevation of lactate dehydrogenase and alpha-hydroxybutyrate dehydrogenase activities in aclacinomycin A-treated hamsters at a dose of 2.0 mg/kg, and an increase in lipoperoxide in adriamycin-treated animals at a dose of 0.5 mg/kg during dosing period. Histologically, both drugs produced separation of myofilaments, swelling of mitochondria, dilation of sarcoplasmic reticulums and decreases in glycogen and lipid particles in myocardium. But aclacinomycin A-treated hamsters rarely showed these alterations after recovery period, whereas adriamycin-treated animals showed separation and necrosis of myofilaments, fibrosis of muscle fibers and formation of myelin figure even after recovery period. These results suggested that cardiotoxicity caused by aclacinomycin A was reversible and milder than that by adriamycin.

Aclarubicin↗
PubMed1980

[Effect of aclacinomycin A on bone marrow (author's transl)].

Japan White rabbits were treated with aclacinomycin A, a new anthracycline antitumor antibiotic, at a dose of 6.25 or 25.0 mg/kg by single intravenous, or 12.5 or 50.0 mg/kg by single oral administration, respectively. Beagle dogs were treated at a dose of 3.0 or 6.0 mg/kg by single intravenous injection. In rabbits in higher dose groups, RBC and WBC counts as well as lymphocyte ratio in peripheral blood decreased on day 1. Nucleated cell counts and erythroid elements in bone marrow decreased to raise M/E ratio (Myeloid/Erythroid ratio) on day 3. In a dog given at 6.0 mg/kg, WBC and platelet counts, lymphocyte and neutrocyte per cents in peripheral blood and also nucleated cells, particularly erythroid elements in bone marrow remarkably decreased on day 3 accompanied with an increase in M/E ratio. These changes were almost completely recovered by day 14 in both animals. No abnormalities were found in lower dose groups. Male Wistar rats, treated with the drug at a dose of 1.5 mg/kg by daily intraperitoneal injection for 30 days, showed slight decreases in peripheral WBC and RBC counts and M/E ratio in bone marrow. No change was observed in rats treated at 0.75 mg/kg and less for 30 days.

Aclarubicin↗
PubMed1980

[Irritative effect of aclacinomycin A on the eye mucous membrane, skin and muscle (author's transl)].

Aclacinomycin A, a new anthracycline antitumor antibiotic, was given to rabbits by single instillation or single intracutaneous injection and to guinea pigs by single subcutaneous or intramuscular injection to examine the irritative effect. Slight dilatation of blood vessel and swelling in the conjunctiva and nictitating membrane were observed in the eyes of rabbits given 1% solution. Edema in the bulbar conjunctiva, iris and cornea was histologically noted. Washing of the eyes after drug instillation prevented these damages. Subcutaneous and intracutaneous injections of 1% solution (0.2 ml) gave hyperemia, swelling and necrosis at injection site. Cellular infiltration, fibrosis and necrosis were histologically detected. Intramuscular injection of 1% solution (0.2 ml) also provided induration and swelling at injection site. Histologically cellular infiltration and necrosis were observed. These irritative effects were much slighter in administration of 0.1% solution. No change was observed with 0.01% solution.

Aclarubicin↗