[The effect of human immunoglobulin for the prevention of the post-transfusion hepatitis following open heart surgery in children (author's transl)].
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Biomedical subjects
Publications and source records attributed to H Ohashi.
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The absorption, distribution and excretion of netilmicin (NTL) in rats were examined by the microbiological assay method. Plasma level and urinary excretion of NTL in rats after intramuscular administration were compared with those of 5 other aminoglycoside antibiotics, gentamicin, sisomicin, dibekacin, amikacin and tobramycin. 1. After intravenous administration, plasma level of NTL declined rapidly with a half-life of about 18 minutes. In the cases of intramuscular, intraperitoneal and subcutaneous administrations, plasma levels reached maximum at 15 minutes and declined with similar half-life as intravenous administration. 2. When 20 mg/kg of NTL was administered intramuscularly, NTL was highly distributed into the kidney, while poorly into the brain. The disappearance rates of NTL from the tissues except the kidney were almost same as that from the plasma. Concentration of NTL in kidney was about 3 times higher than that in plasma at 15 minutes after administration and declined with a half-life of about 7 days. 3. NTL excreted in the bile within 24 hours was only 0.2% of the dose administered (20 mg/kg, i.m.). An average concentration of bile during the first 2 hours was 3 mcg/ml. 4. Irrespective of the route of administration (i.v., i.m., i.p. and s.c.), NTL was excreted rapidly in the urine and 70.0 approximately 81.0% of the dose was recovered within 6 hours. 5. Plasma level and urinary excretion of NTL after intramuscular administration (20 mg/kg) were almost similar to those of 5 other aminoglycoside antibiotics. 6. There was no difference between NTL and GM in plasma level after high dose (100 mg/kg, i.m).
Repeated administration of netilmicin (NTL), a new aminoglycoside antibiotic, to rats at daily intramuscular dose of 10 or 20 mg/kg for 22 days did not affect the plasma level and the plasma half-life of the drug. The concentrations of NTL in the kidney increased markedly after repeated administration, and reached peak level after 8 and 15 doses for 10 and 20 mg/kg, respectively. Cumulative effect of NTL after repeated dose was also observed in the liver, spleen and lung, although the peak concentrations of NTL in these organs were below 1/50 of that in the kidney. Blood and tissue levels of NTL in rats were determined after a single intramuscular administration of 14C-NTL at a dose of 20 mg/kg following 21 repeated intramuscular administrations of NTL at daily dose of 20 mg/kg. The repeated dose of NTL had no effect on the blood level-time curve of radioactivity. The concentration of NTL in the kidney determined by radioassay was about 1/3 of that determined by bioassay, whereas the half-lives in the tissue levels determined by these two assays were nearly identical with each other. The half-life in the lung determined by bioassay was almost identical to that determined by radioassay, whereas the former was rather shorter than the latter in the liver and spleen.
Pharmacokinetics of netilmicin (NTL), a new aminoglycoside antibiotic, injected intramuscularly to Beagle dogs were compared with those of gentamicin (GM), and the relationship between NTL dosage administered and plasma level and urinary excretion was examined. 1. When administered to 6 male Beagle dogs at a dose of 10 mg/kg, the plasma level showed a broad peak (ca. 23 mcg/ml) at 10 to 45 minutes after administration and declined thereafter with half-life of 65 minutes. On the other hand, the plasma level of GM administered at a dose of 10 mg/kg showed a peak (ca. 24mcg/ml) at 15 to 45 minutes after administration and the elimination half-life was 75 minutes. Both of the urinary concentrations of NTL and GM administered at a dose of 10 mg/kg were highest in the 4- to 6-hour urine, whereas NTL and GM recovered in the 24-hour urine were 51.7% and 57.7% of the dose administered, respectively. The pharmacokinetic profile of NTL administered intramuscularly to Beagle dogs appeared to be almost identical to that of GM. 2. The peak plasma level of ca. 50 mcg/ml was obtained at 10 to 60 minutes after administration of NTL at 20 mg/kg, and the half-life was 74 minutes. NTL recovered in the 24-hour urine was 69.7% of the dose administered. 3. TLC-bioautograms showed no biologically active metabolites of NTL in the urine collected from Beagle dogs given the antibiotic intramuscularly.
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Previous work has indicated that a chemoselective resistance controls gastric emptying. By use of meals of glucose or oleate, which were shown to empty spontaneously from dogs' stomachs half as fast as saline, we sought to locate this resistance by studying flow under controlled pressures in various regions of the gastrointestinal tract. In intact dogs, gastric outflow of glucose or oleate rose one-third as fast as outflow of saline as gastric pressure was raised, and this increased resistance to outflow of nutrients was unaffected by truncal vagotomy and pyloroplasty. In fistula dogs, gastroduodenal outflow rose linearly with gastroduodenal pressure gradients; outflow was markedly inhibited in a dose-related manner by intestinal oleate but not glucose. Inhibition by oleate was abolished by pyloroplasty. Glucose or oleate flowed into the small bowel from a barostat only slightly slower than saline. However, there was a strong inhibition of intestinal inflow of all three meals by gastric distension, an effect unaltered by truncal vagotomy. The findings suggest that gastric emptying is controlled by complex interactions among pressures and resistances, both within and beyond the stomach.
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1. Isolated longitudinal muscle strips from the chicken rectum responded to isoprenaline, adrenaline and noradrenaline with a prolonged relaxation. The concentrations required to produce 50% of the maximum relaxation were 1.3 x 10(-8) M for isoprenaline, 1.7 x 10(-8) M for adrenaline and 10(-6) M for noradrenaline. The relaxing potency of isoprenaline is about equal to that of adrenaline, but more than 50 times that of noradrenaline. 2. Propranolol, 3.4 x 10(-6) M, blocked the isoprenaline-induced relaxation, and in the presence of this drug the responses to adrenaline and noradrenaline were converted into small, transient relaxations. The residual relaxation was blocked by phentolamine, 2.6 x 10(-6) M. 3. These catecholamines suppressed spontaneous spike discharge and produced membrane hyperpolarization. Propranolol, 3.4 x 10(-6) M, prevented the inhibitory effects of isoprenaline, and reduced but did not completely abolish those of adrenaline and noradrenaline. 4. Adrenaline and noradrenaline, but not isoprenaline, reduced membrane resistance in some preparations. 5. In the rectal muscle of the chicken, the beta-adrenoceptor mediates a prolonged relaxation and the alpha-adrenoceptor a fast and short-lasting relaxation which is usually obscured by the beta-response and unmasked only after blockade of the beta-adrenoceptors. The alpha- and beta-mediated relaxations are each associated with the suppression of spontaneous spike activity.