Search PubMed⌕ Search

Biomedical subjects

A Sakai

Publications and source records attributed to A Sakai.

At least 343 records · Page 19Linked to original sources
PubMed1987

[Effect of metabolites on the human plasma concentration as total activity after oral administration of rokitamycin. Comparison of three different bioassay methods].

Three different bioassay methods for rokitamycin (TMS-19-Q) were compared to each other in vitro and in vivo. Method I was a paper disc method using Micrococcus luteus ATCC 9341 as the test organism in nutrient agar (pH 8.0), method II was a paper disc method using Streptococcus pyogenes Cook in brain heart infusion agar (pH 7.4) and method III was an agar well method using M. luteus ATCC 9341 in the agar medium provided in the Minimum Requirements for Antibiotic Products of Japan (pH 6.5). Ratios of relative potency of TMS-19-Q and its metabolites calculated from standard curves in human plasma using these bioassay methods, were 1.00:1.13:3.34:0.96 (TMS-19-Q:10"-OH-TMS-19-Q:LM A7:LM V) in method I, 1.00:1.58:0.40 (TMS-19-Q:LM A7:LM V) in method II and 1.00:0.51:0.86:0.114 (TMS-19-Q:10"-OH-TMS-19-Q:LM A7:LM V) in method III. The relative potency obtained from method I, generally used for macrolide antibiotics, greatly contradicted MIC values of TMS-19-Q and its metabolites against clinically isolated 190 strains of Staphylococcus aureus. On the other hand, the relative potency obtained from method III reflected closely MIC values of TMS-19-Q and its metabolites. Therefore, method III should be the most suitable bioassay method to measure the plasma concentration of TMS-19-Q. Plasma concentrations measured by these 3 different methods were compared to each other in vivo, after oral administration of TMS-19-Q at a dose of 1,200 mg to each of fasted healthy volunteers. Values obtained from method I were about 4.3 times higher than those method III.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1987

[Effects of systemic administration of strychnine, L-allylglycine, bicuculline and picrotoxin on the transsynaptic neural destruction in the medullary dorsal horn following transection of the rat inferior alveolar nerve].

Adult rats underwent unilateral transection of the inferior alveolar nerve and subsequent intraperitoneal injection of strychnine (1 mg/kg, 3-23 days) at various posttransectional intervals. When they were sacrificed at 18-30 days posttransectionally, many pyknotic neuronal cell bodies were observed in plastic embedded toluidine blue-stained 1 micron-thick sections of the medullary dorsal horn. They were mostly found in the dorsal part of the dorsal horn ipsilateral to the neurotomy and were more abundant in laminae I/II than in laminae III/IV. Similar pyknotic neurons were found after 1 or 2 days of L-allylglycine administration (55.7 mg/kg/day) at a posttransectional interval of 20 days. Unlike those observed after strychnine treatment, the pyknotic neurons after L-allylglycine treatment were evenly distributed throughout laminae I-IV of the dorsal half of the medullary dorsal horn. Twenty-three days of bicuculline (2 mg/kg/day) or picrotoxin (0.5 mg/kg/day) treatment at an interval of 7 days did not yield pyknotic neurons. The results are discussed in the light of intrinsic synaptic circuitry of the dorsal horn.

Allylglycine↗
PubMed1987

[Studies on the metabolic fate of isepamicin sulfate (HAPA-B). III. Intramuscular, intravenous and drip intravenous administration of HAPA-B in rabbits].

Absorption, distribution, metabolism and excretion of isepamicin sulfate (HAPA-B) were studied following intramuscular, intravenous and drip intravenous administration at doses of 6.25, 25 and 100 mg/kg to rabbits. Plasma concentrations of HAPA-B following intramuscular, intravenous and drip intravenous administration depended on dose levels. Biological half-lives (T1/2), body clearance (Clt) and areas under plasma concentration-time curves (AUC) for different routes of administration were similar in all 3 routes. A theoretical curve for drug concentrations vs. time was obtained using pharmacokinetic parameters calculated from drug concentrations in plasma following a 45-minute drip intravenous administration. From the curve, it was estimated that 60 to 90 minutes would be required to achieve a similar maximum drug concentration in plasma by drip intravenous administration to that obtained by intramuscular administration. Thus, drug concentration patterns obtained following intramuscular administration could be duplicated in drip intravenous administration by regulating the length of time for infusion. The concentration of HAPA-B in tissues obtained following a 15-minute drip intravenous administration reached maximum after 15 minutes at a level higher than that achieved by intramuscular administration, but an hour later, concentrations in tissues including the kidney decreased to similar levels obtained following intramuscular administration and patterns of concentration decrease for drip intravenous administration and intramuscular administration were quite similar to each other thereafter. The drug was rapidly excreted into the urine following any of the 3 routes, and urinary recoveries in 24 hours were 75 approximately 92% of dose amounts for all dose levels tested. Bioautograms on thin-layer chromatographs of 0 approximately 6 hours urine samples obtained following an intramuscular administration of the drug showed a single biologically active bands with similar Rf values to HAPA-B itself. No active metabolite of the drug was detected in the urine.

Aminoglycosides↗
PubMed1987

[Studies on the metabolic fate of isepamicin sulfate (HAPA-B). V. Plasma concentrations of HAPA-B in dogs after multiple administrations].

Plasma concentrations after a single or multiple intramuscular administrations of isepamicin sulfate (HAPA-B) at dose levels of 6.25, 25 and 100 mg/kg to male and female dogs were measured by microbiological assay, and were also compared with those of amikacin at dose levels of 25 and 100 mg/kg. Shapes of plasma concentration curves after multiple administrations of HAPA-B were very similar to those after single administrations at all dosage levels tested. On the other hand, the shape of plasma concentration curve after multiple administration of amikacin at 100 mg/kg was markedly different from that after a single administration.

Amikacin↗
PubMed1987

[Absorption and distribution of rokitamycin in beagle dogs].

Tissue distribution of rokitamycin (TMS-19-Q) was studied after oral administration of 50 mg/kg to fasted Beagle dogs. Tissue concentrations of TMS-19-Q reached their peaks at 1-2 hours after the administration. The order of tissue concentrations of TMS-19-Q was liver greater than kidney greater than spleen greater than lung greater than mesenteric lymph node greater than heart greater than tonsil greater than serum greater than prostate gland greater than uterus greater than skin. At the peak time, drug concentrations in tonsil and lung were about 1.1 and 1.4 times higher, respectively, than that in serum.

Animals↗
PubMed1987

[Studies on the metabolic fate of 14C-rokitamycin. I. Absorption, distribution, metabolism and excretion in rats].

Blood concentrations of 14C-rokitamycin (14C-TMS-19-Q) reached their peaks at 1 hour after a single oral (200 mg/kg) administration to male and female rats, and they were 28.0 +/- 0.8 and 24.9 +/- 2.0 micrograms/ml, respectively. No significant differences were observed between male and female in AUC values or maximum blood concentrations. The distribution of TMS-19-Q was good, and concentrations of 14C were high in liver, kidney, spleen, pancreas, adrenal, pituitary gland, thyroid, trachea, exorbital lacrimal gland, submaxillary gland and bone marrow. During the 72 hours period after a single oral (200 mg/kg) administration of 14C-TMS-19-Q to male rats, 8.0 and 89.6% of the dose were excreted in urine and feces, respectively and a total recovery rate was 97.5% of the dose. During the 48 hours period after a single intraduodenal (200 mg/kg) administration of 14C-TMS-19-Q in male rats, 6.9 and 36.2% of the dose were excreted in urine and bile, respectively. Reabsorption of 14C excreted from the bile was negligible. Absorptions of TMS-19-Q from the duodenum, jejunum, ileum and colon were good, but absorption from the stomach was negligible. Major metabolic reactions of TMS-19-Q were deacylation and hydroxylation, and the major metabolites in rats of TMS-19-Q found in the plasma, urine and bile after oral and intraduodenal administration were 10"-OH-TMS-19-Q, leucomycin A7, leucomycin V and 14-OH-leucomycin V.

Animals↗
PubMed1987

[Studies on the metabolic fate of 14C-rokitamycin. II. Accumulation of radioactivity in rats after consecutive oral administration].

After a consecutive oral administration of 200 mg/kg/day of 14C-rokitamycin (TMS-19-Q) daily for 28 days to male rats, the accumulation of radioactivity in tissues and its disappearance after the cessation of the administration was studied. Blood concentrations at peak times and 24 hours after each administration were determined daily. Both values increased gradually until the 14th day and thereafter remained roughly constant. The extent of elimination of radioactivity from the blood was practically not affected by the consecutive administration. Affinities of radioactivity to the liver, kidney, spleen, adrenal, pituitary gland, preputial gland, thyroid, intraorbital lacrimal gland and bone marrow were comparatively higher than those to other tissues. Tissue concentrations in the above mentioned tissues at the 1st day after the completion of consecutive administrations for 14 and 28 days were 2.6-6.1 and 3.2-6.8 times higher, respectively, than those at the 1st day after a single administration. The elimination of radioactivity from the tissue after the consecutive administration for 28 days was slightly slower than that after a single administration. In the consecutive daily administration for 28 days, the metabolic fate of radioactivity reached a steady state after 14 days of consecutive daily administration. Hence, the accumulation of the radioactivity did not particularly occurred. During the consecutive administration, recoveries of radioactivity in the urine and feces were almost at a constant rates, with 8.0 and 93.8% of the total radioactivity given excreted in the urine and feces, respectively, within 10 days after the last administration.

Administration, Oral↗
PubMed1987

[Studies on the metabolic fate of 14C-rokitamycin. III. Transmigration to fetus or milk].

Transmigration of 14C-radioactivity to fetus or milk were studied in 17-18 day-pregnant rats and mother rats on the 14th day after parturition after a single oral administration of 14C-rokitamycin (TMS-19-Q) at a dose of 200 mg/kg. The blood concentration of the drug in the mother reached a maximum level of 22.8 micrograms/ml at 2 hours after administration. Maximum concentrations of TMS-19-Q in placenta, ovary and uterus were attained in 2 hours, and were 28.9, 26.0 and 26.2 micrograms/g, respectively. The distribution to these tissues were considered good. The maximum concentration of TMS-19-Q in the amniotic fluid was attained in 2 hours, at a level of 5.4 micrograms/ml. The transmigration to the amniotic fluid was considered poor. The maximum concentration of the drug in the fetus was achieved in 2 hours at a level of 13.7 micrograms/g. Maximum concentrations of the drug in fetal liver and brain were attained in 4 hours, and were 32.8 and 11.4 micrograms/g, respectively. Whole body autoradiography was done when the radioactivity in maternal blood reached peak concentration. It was found that radioactivities in placenta and fetal membrane were similar to the radioactivity in maternal blood, while the radioactivity in fetal brain was considerably lower than that in maternal blood. Maximum concentrations were found at 1 hour in the blood and at 4 hours in the milk, and were 14.8 and 21.5 micrograms/ml, respectively. Transmigration to the milk was good.

Amniotic Fluid↗
PubMed1987

[Studies on the metabolic fate of 14C-rokitamycin. IV. Absorption, metabolism and excretion in dogs].

Absorption, metabolism and excretion of rokitamycin (TMS-19-Q), were studied after oral (50 mg/kg), intraduodenal (50 mg/kg) and intravenous (10 mg/kg) administrations of 14C-TMS-19-Q to male dogs. Maximum blood and plasma concentrations of the drug reached at 2 hours after oral administration, and they were 11.1 and 14.3 micrograms/ml, respectively. Maximum blood and plasma concentrations reached at 30 minutes after intraduodenal administration, and they were 10.7 and 12.0 micrograms/ml, respectively. Blood and plasma concentrations at 3 minutes after intravenous administration were 8.4 and 11.1 micrograms/ml, respectively. At 24 hours, they were 0.6 and 1.7 micrograms/ml, respectively. During the first 72 hours period after oral administration, 12.8 and 82.6% of the dose were excreted in the urine and feces, respectively. A total recovery rate was 95.4% of the dose. During the first 72 hours period after intravenous administration, 19.4 and 75.3% of the dose were excreted in the urine and feces, respectively. A total recovery rate was 94.7% of the dose. During the first 24 hours period after intraduodenal administration, 18.0 and 48.3% of the dose were excreted in the urine and bile, respectively. A total recovery rate was 66.3% of the dose. Major metabolic reactions on TMS-19-Q were deacylation and hydroxylation, and the major metabolites of TMS-19-Q found in the plasma urine and bile after intraduodenal administration to dogs were 10"-OH-TMS-19-Q, LM A7, LM V and 14-OH-LM V.

Administration, Oral↗