摘要:

AbstractThe effect of colchicine (1 mg/kg intraperitoneally on two successive days) on the absorption of isoniazid, quinidine and sulphafurazole (sulfisoxazole) from the rat small intestine was studiedin situandin vitro.Colchicine produced two different types of histological damage in the small intestine, one with degenerative and the other with regenerative changes predominating. The small intestinal surface area was variably reduced. The colchicine‐treated rats were lethargic and hypothermic as compared to controls. Colchicine retarded the disappearance of fluid and all three drugs from the small intestinal lumenin situ2 days after the first colchicine injection.In vitrothe total amounts of fluid and drugs passed through the intestinal wall were not significantly changed by colchicine, although there was a slight tendency towards an increased absorption of quinidine. Hence, colchicine as an antimitotic drug decreases drug absorption from the rat small intestinein situ, apparently due to the decreased surface area of the small intestine, the decreased water flux through the intestinal wall, the retarded intestinal motility and hypothermia of the rats.In vitrothe changes are small, which makes thein vitrotests less suitable for studying the effect of colchicine on absorptio

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1978.tb02262.x

出版商:Blackwell Publishing Ltd    

年代:1978

数据来源: WILEY

摘要:

AbstractSome weak organic acids are eliminated from the brain by an acid transport system. The question arose is this system also used to transport drugs out of the brain? In that case probenecid pretreatment (100 mg/kg subcutaneously) should influence the induction time of a slightly lipid soluble barbiturate (barbital) which penetrates into the brain slowly, more than the induction time of a very lipid soluble barbiturate (hexobarbital). In the first experiment barbital (200 mg/kg) was given intraperitoneally and in the second experiment barbital (150 mg/kg) was infused intravenously during 10 min. In both experiments loss of righting reflex occurred more rapidly after pretreatment with probenecid compared with pretreatment with saline. Only in the second experiment did probenecid significantly increase the time during which the righting reflex was lost. In the next experiment hexobarbital was infused intravenously at a rate of 0.25 mg/kg/sec. until a burst suppression which lasted 1 sec. or more was seen in a concomitant EEG‐record. When this »silent second« occurred the infusion was stopped and the ensuing anaesthesia times recorded. Probenecid had no effect on the induction when studied with this method, but the ensuing anaesthesia times were increased. The hypothesis of an acid transport system out of the brain was thus not refuted by these experimental results. Studies of brain concentrations of barbital also supported this finding. After 200 mg/kg intraperitoneally the concentration of barbital in the brain was higher after pretreatment with probenecid as compared to saline pretreated controls i.e. at times corresponding to the induction times in the in vivo experiments. No difference was found in the serum levels of barbi

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1978.tb02263.x

出版商:Blackwell Publishing Ltd    

年代:1978

数据来源: WILEY

摘要:

AbstractRats were injected with one of five drugs alleged to inhibit brain prostaglandin (PG) synthesis: indomethacin, diclofenac, naproxen, aspirin and paracetamol. Animals were killed after 30 min. and the endogenous formation of PGF2αand PGE2in brain homogenates was measured by mass fragmentography using deuterium labelled PGF2αand PGE2as internal standards. Diclofenac, indomethacin, and naproxen inhibited dose dependently, the synthesis of PGF2α. The ED50 for diclofenac was 0.4 mg/kg, for indomethacin 1 mg/kg and for naproxen 2 mg/kg. In equieffective doses indomethacin had the longest duration. The time taken for the inhibition to decline to half its maximal value was 32 hrs for indomethacin and about 15 hrs for diclofenac and naproxen. Under the present conditions aspirin and paracetamol failed to produce significant reduction of PG synthesis in the rat brain homogenates in doses up to 100 mg/

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1978.tb02264.x

出版商:Blackwell Publishing Ltd    

年代:1978

数据来源: WILEY

摘要:

AbstractThe distribution of [14C]‐labelled aflatoxin B1has been studied in mice with the aid of whole‐body autoradiography. In addition to the localisation of labelled aflatoxin B1and/or its metabolites in the liver, bile, kidney, lung and urine an uptake of14C in the pigment of the Harderian gland and the eye was observed. Uptake of radioactivity was also found in the eyes of the foetuses although their livers did not accumulate radioactiv

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1978.tb02265.x

出版商:Blackwell Publishing Ltd    

年代:1978

数据来源: WILEY

摘要:

AbstractThe effects of different compounds on the inhibition of choline acetyltransferase in guinea pig cornea have been studied. N‐hydroxyethyl‐4(naphthylvinyl)pyridinium bromide inhibited the enzyme in the cornea when a 0.5% solution was applied topically to the eye. The inhibition could not be explained by redistribution of the inhibitor after homogenization of the tissue. Inhibition of the enzyme was slowly reversed and nearly full enzyme activity was obtained when the eye was left intact for 48 hrs. N‐methyl‐4(naphthylvinyl)pyridinium bromide was a less efficient inhibitorin vivoand no inhibition was found with bromo acetonyl trimethylammonium bromide or acryloylcholine. Corneal ChAT was inhibited by the application of 3‐methyl‐5‐methoxyphenyl pyridinium bromide, but the mechanism was obscured by the compound causing corneal oedema. The investigation shows that epithelium of the cornea can be used to test thein vivoeffect of choline acetyltransfera

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1978.tb02266.x

出版商:Blackwell Publishing Ltd    

年代:1978

数据来源: WILEY

摘要:

AbstractThe metabolism of zearalenone in rat liver has been investigated. The studies were performed mainly with liver homogenate, though isolated microsomes and hepatocytes have also been used. Zearalenone was metabolized along two principal pathways, conjugation with glucuronic acid, which was the main route and reduction to an isomer of zearalenol. In no case, however, could all zearalenone metabolized be accounted for as conjugated zearalenone and free and conjugated zearalenol. Therefore another, so far unknown metabolite cannot be excluded. Reduction to zearalenol could be increased three times by the addition of NADH (or NADPH) and is probably catalyzed by a hydroxysteroid dehydrogenase. Some 25–50 per cent of the zearalenol could be conjugated, depending on the incubation conditions. The capacity of hepatocytes to eliminate zearalenone was estimated to be about 100 μg per gram of liver in one hour. With a liver homogenate the highest value obtained was 82

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1978.tb02267.x

出版商:Blackwell Publishing Ltd    

年代:1978

数据来源: WILEY

摘要:

AbstractIsometric tension was recorded in ring preparations of human peripherial arteries and veins contracted by potassium (127 mM) and noradrenaline (1.8 × 10‐5M). In theveins, nifedipine had a marked relaxing effect on contractions induced by both agents, and also reduced the contractile amplitude when added prior to stimulation. The inhibiting effect of nifedipine was more marked on the potassium than on the noradrenaline‐evoked responses. This was in contrast to verapamil, which inhibited the noradrenaline‐induced contractions significantly more, than those produced by potassium. After immersion of the vein preparations in calcium‐free medium for 30 min., the potassium contracture decreased to 26±2.0% (mean ± S.E.M.) of the response in normal Krebs solution, and the noradrenaline‐evoked response to 7.1±0.8%. The responses to both agents were completely restored when the calcium concentration was increased from 0 to 4 mM. Nifedipine (1.5 × 10‐7M) depressed the potassium contracture in calcium‐free solution to 7.3±1.6%, and the noradrenaline response to 5.5±1.6%; on addition of calcium, the response elicited by potassium increased to 16±1.7%, and that by noradrenaline to 56±8.6%. Compared with its actions on the veins, the effect of nifedipine on thearterialpreparations was less pronounced. In the arteries, too, the inhibiting effect of nifedipine was significantly more pronounced on the potassium than on the noradrenaline‐induced contraction. Immersion for 30 min. in calcium‐free medium reduced the response to potassium to 61±6.0% and that to noradrenaline to 68±5.6% of the control in normal Krebs. Nifedipine (2.9 × 10‐7M) further reduced the potassium contraction to 20±4.0%; the response to noradrenaline was unaffect

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1978.tb02268.x

出版商:Blackwell Publishing Ltd    

年代:1978

数据来源: WILEY

摘要:

AbstractCytochrome P‐450 in mouse liver microsomes was characterized by SDS‐polyacrylamide gel electrophoresis after intraperitoneal injection of 80 mg phenobarbital, 4.5 and 45 mg acrylamide and 60 and 600 mg methylmethacrylate per kg body weight each day for four days. Four different forms of cytochrome P‐450 with molecular weights of 47,000, 50,000, 54,000 and 56,000 were identified by staining for peroxidase activity and protein. The amount of cytochrome P‐450 with a molecular weight of 47,000 (MLvMc P‐45047) decreased in the phenobarbital group and in both acrylamide groups. After methylmethacrylate treatment, this form increased at the low dose but was totally repressed at the high dose. The cytochrome P‐450 form with a molecular weight of 50,000 (MLvMc P‐45050) was significantly increased only in the phenobarbital group. An increase in the total amount of cytochrome P‐450 was only observed following treatment wit

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1978.tb02269.x

出版商:Blackwell Publishing Ltd    

年代:1978

数据来源: WILEY

摘要:

AbstractThe bioavailabilities of two tablet brands carbamazepine (CBZ) (Tegretol®, A; Neurotol®, B) were compared with two new experimental preparations (C, D). Formulation A showed a more sustained release nature than did the other formulations. The AUCs0→∞gave no significant differences between treatment A and three other treatments. However, if AUC0→72was calculated instead of AUC0→∞, the preparation A gave the significantly lower bioavailability than the other compounds. Formulations A and B are marketed as generically equivalent preparations in Finland. However, their pharmacokinetic parameters after a single dose wer

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1978.tb02270.x

出版商:Blackwell Publishing Ltd    

年代:1978

数据来源: WILEY

摘要:

AbstractUptake studies, using radioactive labelled glucuronides, have demonstrated the ability of 4‐nitrophenyl glucuronide and phenolphthalein glucuronide to enter isolated rat hepatocytes. Of these glucuronides 4‐nitrophenyl glucuronide was distributed in a similar manner to O‐methylglucose, whereas phenolphthalein glucuronide was bound to cellular constituents. Phenolphthalein glucuronide had an effect on the conjugation of harmol in the isolated hepatocytes when glucuronidation was found to be markedly inhibited and sulphation slightly stimulated. The glucuronidation of 4‐nitrophenol, 4‐methylumbelliferone and harmol in native microsomes was inhibited by phenolphthalein glucuronide. 4‐Nitrophenyl glucuronide and also naphthyl glucuronide were without effect both in hepatocytes and microsomes. In control hepatocytes harmine was metabolized to form harmolsulphate mainly. Phenolphthalein glucuronide only affected this metabolic pattern to a minor extent. However, in hepatocytes from phenobarbital treated rats, where the rate of harmine metabolism is increased about five times and the main metabolite is harmol glucuronide, phenolphthalein glucuronide inhibited the formation of the conjugate with a concomitant increase in

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1978.tb02271.x

出版商:Blackwell Publishing Ltd    

年代:1978

数据来源: WILEY