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991.
J A Scatina D R Hicks M Kraml M N Cayen 《Xenobiotica; the fate of foreign compounds in biological systems》1989,19(9):991-1002
1. The disposition of AY-30,068 (I), a new tetrahydrocarbazole analgesic drug, was studied in mice, rats, dogs, rhesus monkeys, and man. 2. Oral doses of the 14C-labelled drug in aqueous solution were well absorbed in rodents, but absorption of oral doses of the crystalline drug in dogs was poor. Due to the virtual absence of serum metabolites in rats and dogs, the bioavailability of I was nearly identical to the extent of absorption. Although a small first-pass effect was observed in mice, unchanged I represented a major portion of serum radioactivity. 3. A linear increase in the serum concentrations of I occurred at doses between 0.05 and 25 mg/kg in rats, 0.1 and 50 mg/kg in dogs, and 1-160 mg in man. In rhesus monkeys given a 0.5 mg/kg oral dose, the Cmax and AUC of I were similar to values obtained following a corresponding dose in dogs. 4. After i.v. administration of a 1.0 mg/kg dose the terminal elimination half-life (t1/2 beta) of I was 4 h in mice and 9-10 h in rats and dogs. In rodents, dogs, and several human subjects, the elimination of I was interrupted by secondary peaks. Enterohepatic circulation was confirmed in bile duct cannulated rats, where the t1/2 beta of I was decreased to 2.4 h. In rodents the serum clearance and apparent volume of distribution of I were 0.04-0.2 l/kg.h and 0.5-0.8 l/kg, respectively, and 0.6 l/kg.h and 9.8 l/kg in dogs. 5. In rodents and dogs dosed with 14C-labelled I, radioactivity was excreted almost entirely in the faeces. No unchanged I was detected in rat bile, while about 70% of the radioactivity corresponded to conjugates of parent drug. 相似文献
992.
Dermal absorption of the insecticide lindane was determined following topical application of ring 14C-labeled lindane to the tail of Sprague-Dawley rats. The tail was tested as a practical alternative to the rat mid-dorsal (back) region, and the data obtained were compared to those with rat back and with those of rhesus monkeys in our previous reports. There was no significant difference between total percentage urinary 14C recovery for rats dosed on the tail with occlusive tail covers (52 +/- 6.2%; t1/2 = 2.7 d) compared to those with nonocclusive covers (55 +/- 4.4%; t1/2 = 2.9 d). Neither the total percentage urinary recovery nor the t1/2 values obtained for the rat tail and rat back models differed significantly. Carbon-14 activity was still detectable in urine samples taken after 72 d post-treatment. However, an extensive tissue analysis failed to demonstrate 14C activity persisting at 72 d, with the exception of trace levels detected in blood serum and tail tissue. Advantages of the rat tail model are highlighted. 相似文献
993.
Serum aminogram changes were prospectively studied in 95 patients with enteric fistula and intraabdominal infection who was under total parenteral nutrition (TPN) therapy with Anfuming 14s. In patients with sepsis and starvation, the aminogram showed remarkably low total free amino acids before TPN therapy. In 81 survivors, free amino acids increased gradually to normal in 2 weeks after use of TPN and in 14 dead cases increased rapidly to a significantly higher peak at terminal stage. Both in survivors and nonsurvivors, phenylalanine level remained high during the study. In response to infection, proline was also elevated but to a lesser degree; the ratio of branched chain amino acid (BCAA) to aromatic amino acid (AAA) was lower than normal and the decrease of arginine was parallel to the severity of infection. We conclude that the ideal amino acids preparation for the starvated and septic patients should be high in BCAA and arginine but low in phenylalanine, administration of inappropriate exogenous amino acids in decompensated metabolic septic patients may bring about more harm than benefit, and in septic patients that the levels of serum phenylalanine and proline are elevated persistently along with the decrease of arginine level is a useful prognostic indication. 相似文献
994.
M K Song W Y Shin N F Adham N V Costea 《The American journal of clinical nutrition》1989,49(4):701-707
The effects of different amounts of dietary zinc on the Zn absorption rate and on Zn, calcium and magnesium concentrations in tissues of MOPC 104E tumor-bearing Balb/c mice were determined. The Zn absorption rate was inversely related to the amounts of Zn in their diets and was lower than that of nontumor-bearing control mice fed a laboratory mice chow. Zn concentrations of tumor-bearing mice were also low compared with control mice but tumor Zn concentrations, regardless of the concentrations of Zn in the diets, were higher than those of normal tissues of the host other than the pancreas. Ca concentrations in tumor and tissues of tumor-bearing mice were higher than in control animals but Mg concentrations in tissues of tumor-bearing mice appeared to be similar to those of control mice. Results suggest that tumor-bearing mice have a lower intestinal Zn absorption capacity and a higher Zn uptake rate causing other tissues to become hypozincemic and hypercalcemic. 相似文献
995.
The contractile response of isolated guinea pigs common bile ducts (CBD) to transmural electrical stimulation and the effects of morphine and naloxone was studied. Contractile responses increased as a function of stimulus frequency. In the absence of naloxone morphine inhibited the contractile response to electrical stimulation in a dose-dependent manner. Naloxone prevented the inhibitory effect of morphine on the contractile response to electrical stimulation. We conclude that smooth muscle of the CBD in guinea pig is functional and can contribute to biliary motility, and that opiate receptors exist in nerve elements in the CBD. 相似文献
996.
Dihydroxyacetone (DHA), a browning agent, protects photosensitive rats and humans against long ultraviolet radiation (UVA, 320-400 nm) and visible (blue) light. The photoprotective efficacy of DHA and structurally similar compounds was assessed as prevention of edema in the paws of psoralen-sensitized rats, after exposure to blacklight fluorescent lamps. Methylglyoxal produced a yellow-brown color and provided nearly the same protection as DHA, whereas monohydroxyacetone did not color the skin and afforded little or no protection. Glyceraldehyde provided a moderate amount of protection, which was enhanced by prior exposure of the agent to alkaline pH. A solution of 5-hydroxymethylfurfuraldehyde was yellow and provided minimal protection by staining the skin rather than browning it. We conclude that the ability to produce a brown color in skin is a useful criterion for screening compounds for photoprotective efficacy against UVA radiation. 相似文献
997.
A clinical phase I study for T-2588 was carried out in 25 healthy male volunteers. Each volunteer received T-2588 in one of the following doses: 100 mg capsule or tablet as a single oral administration in fasting or non-fasting state, 200 or 400 mg capsule as a single oral administration in non-fasting state or 300 or 600 mg daily for 14 approximately 15 days as a repeated administration in non-fasting state. The results are summarized below. No subjective or objective adverse effects were noted after a single oral administration. But repeated dose of 300 mg daily for 15 days and 600 mg daily for 14 days brought about abdominal distension in 1 case and soft stool in 1 case, respectively. As an abnormal change in clinical laboratory findings, 1 case with slight increase in transaminase after a single administration and 3 cases with slight increases in transaminase after repeated doses were observed. Time to reach a maximum concentration of T-2525 in blood (Tmax) was longer in subjects at non-fasting states than subjects in fasting states. Maximum blood concentration was lower in the latter than in the former. Urinary excretion rate in 8 hours after an oral administration was 19 approximately 28% and it was higher in non-fasting subject than in fasting subject. No accumulation of T-2588 was noted after repeated doses. 相似文献
998.
T. S. Lie M. Höfer Ch. Höhnke 《Langenbeck's archives of surgery / Deutsche Gesellschaft fur Chirurgie》1987,372(1):893-894
Zusammenfassung Bei einem 55jährigen Mann wurde 7 Monate nach orthotoper Lebertransplantation eine Lungentuberkulose diagnostiziert. Die tuberculostatische Therapie erfolgte mit Isoniazid (3 x 0,2 g/Wo) und Ethambutol (1,6 g/d) über 11 Monate. Nach 3 Monaten waren keine Mycobakte rien mehr nachweisbar, und der Patient ist im 3. Jahr nach Transplantation ohne Zeichen einer aktiven Tuberkulose in gutem Gesundheitszustand bei guter Transplantatfunktion. Die Tuberculostatica-Dosierung sollte je nach Metabolisierungsleistung des Transplantats reduziert werden. Bei Beachtung dieses Kardinalpunktes könnte eine Tuberkulose nach Lebertransplantation erfolgreich behandelt werden. 相似文献
999.
1000.
Phase I study of high-dose cytosine arabinoside and etoposide in patients with advanced malignancies
Bayard L. Powell Hyman B. Muss Robert L. Capizzi Mary E. Caponera Douglas R. White Patricia J. Zekan James N. Atkins Don V. Jackson Jr. Frederick Richards II John B. Craig Julia M. Cruz Charles L. Spurr 《Cancer chemotherapy and pharmacology》1987,19(3):250-252
Summary Cytosine arabinsodie (ara-C) and etoposide (VP-16) display synergy in the laboratory. Twenty-six patients participated in a phase I study of high-dose ara-C in combination with VP-16. The dose of VP-16 was held constant at 50 mg/m2 as an intermittent infusion over 33 h; escalating doses of ara-C were given as infusions during hours 9–12 and 21–24. Myelosuppression was the dose-limiting toxicity and occurred with doses considerably less than those expected from studies of the two drugs as single agents. The suggested initial doses for phase II trials with this schedule are 750 mg/m2×2 doses of ara-C and 50 mg/m2 of VP-16. Nonhematologic toxicity was minimal; therefore, further dose escalation is feasible in patients in whom myelosuppression is acceptable.Supported in part by grants from the National Cancer Institute (CA-12197 and CA-09422) and the American Cancer Society CF-85-182 相似文献