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  • Articles  (33)
  • metabolism  (33)
  • Springer  (33)
  • Annual Reviews
  • International Union of Crystallography
  • PANGAEA
  • 1990-1994  (18)
  • 1980-1984  (15)
  • 1991  (18)
  • 1984  (15)
  • Medicine  (25)
  • Chemistry and Pharmacology  (21)
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  • Articles  (33)
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  • Springer  (33)
  • Annual Reviews
  • International Union of Crystallography
  • PANGAEA
  • Wiley-Blackwell  (2)
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  • 1990-1994  (18)
  • 1980-1984  (15)
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  • 1
    Electronic Resource
    Electronic Resource
    Synthesis and metabolism of vertebrate-type steroids by tissues of insects: A critical evaluation (1991)
    Springer
    Cellular and molecular life sciences 47 (1991), S. 687-698 
    Details
    ISSN: 1420-9071
    Keywords: Vertebrate-type steroids ; insects ; metabolism ; hormones
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary This review covers the synthesis and the metabolism of vertebrate-type steroids (progesterone, testosterone, estradiol, corticosteroids) by insect tissues and discusses the significance of the reactions for insect physiology. Biosynthesis of vertebrate-type steroids from cholesterol hitherto has been demonstrated in only two insect species, i.e. the water beetleAcilius sulcatus (Coleoptera) and the tobacco hornwormManduca sexta (Lepidoptera). InAcilius, steroid synthesis is associated with exosecretion (chemical defense). Nothing, however, is known about a physiological role of the C21 steroid conjugate present in ovaries and eggs ofManduca. No synthesis of vertebrate-type steroids was observed in any other insect investigated to date. Most metabolic conversions of steroids by insects concerned oxidoreduction of oxygen groups (hydroxysteroid dehydrogenase activity) and (polar and apolar) conjugate formation. All important enzymatic steps involved in synthesis and catabolism, as known from studies with tissues of vertebrates, were not, or hardly observed. The conclusion is drawn that typical vertebrate-type (C21, C19 and C18) steroids probably do not act as physiologically active substances in insects.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01958817
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  • 2
    Electronic Resource
    Electronic Resource
    Phospholipid metabolism in pancreatic islets (1984)
    Springer
    Cellular and molecular life sciences 40 (1984), S. 1085-1091 
    Details
    ISSN: 1420-9071
    Keywords: Pancreatic islets ; metabolism ; phospholipid
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Conclusions The secretion of insulin can be elicited by a wide spectrum of stimuli including nutrients, hormones and neurotransmitters as well as a large number of pharmacological agents such as tumor-promoters and sulphonylureas. The diversity of these secretagogues suggests that islets may be activated through a number of distinct biochemical mechanisms. The work discussed in this review suggests that certain of the above-mentioned secretagogues, especially nutrient and neurotransmitter stimuli, may induce insulin secretion by a mechanism involving enhanced metabolism of inositol-containing lipids. The way in which this process is coupled to secretion is not known, although several possibilities exist. The hydrolysis of phosphoinositides and release of inositol phosphates may result, respectively in altered calcium permeability of the plasma membrane and mobilization of calcium from intracellular sources. The accompanying production of diacylglycerol might also influence membrane permeability and fluidity and also lead to activation of protein kinase C. Diacylglycerol can be phosphorylated to form phosphatidic acid which may play a role as an endogenous ionophore. Finally, inositol lipid breakdown could lead, through diacylglycerol and/or phosphatidic intermediates, to the liberation of arachidonic acid and subsequent conversion to active metabolites of the cyclo-oxygenase and lipoxygenase pathways. Thus, enhanced phospholipid metabolism in islets could, theoretically, result in the generation of a range of intracellular signals which mediate or modulate insulin secretion during stimulation by certain types of secretagogues. Continued investigation is clearly neccessary in order to elucidate the mechanisms by which such secretagogues provoke increased phospholipid metabolism and to understand the role(s) of this process in the regulation of islet function.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01971455
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  • 3
    Electronic Resource
    Electronic Resource
    Physiological importance of ω-3/ω-6 polyunsaturated fatty acids in man. An overview of still unresolved and controversial questions (1991)
    Springer
    Cellular and molecular life sciences 47 (1991), S. 172-178 
    Details
    ISSN: 1420-9071
    Keywords: Essential fatty acids ; deficiency ; metabolism ; mammals
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The ‘essentiality’ of (ω-6) and (ω-3) fatty acids in mammals is well known. Nevertheless, some important points remain unclear concerning their implication in physiology. After a short discussion about the definition of essential fatty acids deficiency, this brief overview deals with some of these points, pointing out some of the unresolved questions. Different subjects are approached concerning the (ω-6) and (ω-3) fatty acids metabolism: desaturases, eicosanoids, production, as well as some of their metabolic effects on cell membranes, intestinal function, glucose and lipid metabolism, haemorheology.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01945421
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  • 4
    Electronic Resource
    Electronic Resource
    Ciclosporin metabolite pattern in blood and urine of kidney graft patients in relation to liver function (1991)
    Springer
    European journal of clinical pharmacology 40 (1991), S. 565-569 
    Details
    ISSN: 1432-1041
    Keywords: Ciclosporin ; metabolism ; metabolites ; liver dysfunction ; kidney transplantation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Ciclosporin, an immunosuppressant, is metabolized by the liver cytochrome P450 system. Changes in the pattern of its metabolites in blood and urine in patients with disturbed liver function have been studied. Forty seven kidney graft patients receiving 2.9 mg/kg/d ciclosporin b.i.d., and no additional medication that would interfere with ciclosporin metabolism, were allocated to three groups according to liver function: I with normal liver function (n=19), II with elevated liver enzyme activity or bilirubin concentration in serum (n=20), and III with cholestasis (n=8). Ciclosporin and 17 metabolites were determined in blood and 24 h-urine. In blood the trough concentrations of metabolites M19 and M1A were significantly higher in group III than in groups I and II. The total quantity of metabolites excreted in 24 h-urine was significantly different for H230, M4N69 and M1A (group III〉I=II). Renal excretion of the daily dose of ciclosporin in patients in group I was 2.7%, group II 3% and group III 5.7%. In group III compared to group I the ciclosporin metabolite pattern was shifted to a relatively higher concentration of M19 in blood and of H 230, M19 and M1A in urine. Since high ciclosporin metabolite concentrations appear to be associated with nephrotoxicity, the metabolite pattern in patients with impaired liver function should be monitored.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00279971
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  • 5
    Electronic Resource
    Electronic Resource
    Lack of effect of paracetamol on the pharmacokinetics and metabolism of codeine in man (1991)
    Springer
    European journal of clinical pharmacology 41 (1991), S. 379-382 
    Details
    ISSN: 1432-1041
    Keywords: Codeine ; paracetamol ; codeine-6-glucuronide ; pharmacokinetics ; metabolism ; partial clearance ; drug interaction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Plasma and urine concentrations of codeine and its measurable metabolites were determined by HPLC in six healthy subjects after a single 30 mg oral dose of codeine either alone or after 7 doses of 1 g paracetamol 8 hourly. After codeine alone, the t1/2 (h), AUC (μmol·l−1·h) and CLR (ml·min−1) for codeine were 2.2, 0.81, and 252 respectively. These were not significantly altered by paracetamol: 2.2, 0.84, and 291 respectively. For codeine-6-glucuronide the values were 2.4, 22.0, and 29.7 respectively. These were not significantly different from those after codeine plus paracetamol: 2.4, 21.9, and 39.6. There were no significant differences between the two treatments in the apparent partial clearances (ml·min−1) of codeine to morphine (88 codeine alone, 70 codeine plus paracetamol), to norcodeine (71 codeine alone, 88 codeine plus paracetamol), and to codeine-6-glucoronide (820 codeine alone, 1022 codeine plus paracetamol). The urinary excretion of codeine-6-glucuronide, morphine, norcodeine, and codeine were not significantly different between the two treatments.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00314972
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  • 6
    Electronic Resource
    Electronic Resource
    Fibrates and triglyceride metabolism (1991)
    Springer
    European journal of clinical pharmacology 40 (1991), S. S41 
    Details
    ISSN: 1432-1041
    Keywords: Lipoproteins ; metabolism ; hypertriglyceridemia ; fibrates
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Some mechanisms of the triglyceride-lowering effects of fibrates in patients with hypertriglyceridemia are reviewed. One main effect of the fibrates is the stimulation of lipoprotein lipase activities in plasma as well as in adipose tissue. According to this increase in the degradational activity VLDL catabolism is stimulated, as has been demonstrated for VLDL apo B and VLDL triglycerides. In addition, the composition of hypertriglyceridemic LDL is reverted towards normal. Furthermore, the increased degradation via the nonreceptor pathway is decreased by fibrate treatment, thus lowering the atherogenic potential of triglyceride-rich lipoproteins. But additionally the degree of postprandial hypertriglyceridemia is lowered by fibrates.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01409407
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  • 7
    Electronic Resource
    Electronic Resource
    Polymorphic flecainide disposition under conditions of uncontrolled urine flow and pH (1991)
    Springer
    European journal of clinical pharmacology 40 (1991), S. 155-162 
    Details
    ISSN: 1432-1041
    Keywords: Flecainide ; sparteine/debrisoquine polymorphism ; metabolism ; enantiomers ; pharmacokinetics ; stereoselectivity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of R- and S-flecainide have been determined in five poor (PM) and five extensive (EM) metabolisers of sparteine/debrisoquine under conditions of uncontrolled urine flow and pH. The half-lives of R- and S-flecainide in PMs (R 19.3 h; S 16.1 h) were approximately twice those observed in EMs (R 8.8 h; S 9.1 h). The apparent oral clearances of R- and S-flecainide were lower in PMs (R 313 ml·min−1; S 379 ml·min−1) than in EMs (R 783 ml·min−1; S 828 ml·min−1). The renal clearance, however, was comparable for both enantiomers in both EMs and PMs, and therefore the phenotypic differences in flecainide disposition observed must be due to differences in metabolic clearance. The nonrenal clearance of both enantiomers was significantly lower in poor (R 123 ml·min−1; S 201 ml·min−1) relative to extensive metabolisers (R 533 ml·min−1; S 586 ml·min−1). The partial clearance to the two major metabolites meta-O-dealkylated flecainide (MODF) and the meta-O-dealkylated lactam of flecainide (MODLF) was significantly lower in poor (62 ml·min−1) than extensive (267 ml·min−1) metabolisers. The impairment in flecainide metabolism in poor metabolisers of sparteine/debrisoquine has therefore been confirmed. Under conditions reflecting the clinical situation the difference in disposition between EMs and PMs would be considerable. However, it may be predicted that at standard doses concentrations greater than 1000 ng·ml−1 would not be attained in the PMs studied. The serum protein binding of R- and S-flecainide was studied in each subject and no differences between the enantiomers or the phenotypes were observed (Free fraction EM: R 0.43; S 0.42; PM R: 0.46; S: 0.46). Enantioselective disposition was noted in all PMs studied, due to a significantly lower nonrenal clearance of the R-enantiomer. In extensive metaboliser subjects, considerable interindividual variation in the enantioselective disposition of flecainide was noted, ranging from metabolism favouring either enantiomer to the absence of any selectivity.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00280070
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  • 8
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of estramustine phosphate (Estracyt®) in prostatic cancer patients (1984)
    Springer
    European journal of clinical pharmacology 26 (1984), S. 113-119 
    Details
    ISSN: 1432-1041
    Keywords: estramustine phosphate ; prostatic cancer ; pharmacokinetics ; metabolism ; estramustine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of estramustine phosphate (EMP) was studied in five prostatic cancer patients given single i.v. and oral doses of EMP in a cross-over study. Plasma and urinary concentrations of parent drug, estramustine, estromustine (the estrone analogue), estradiol and estrone were followed for 32 h. The elimination of intravenous EMP from plasma was biphasic. The mean volumes of distribution were small, being 43 and 108 ml/kg for the central and peripheral compartments, respectively. The plasma clearance was 64 ml/kg/h, and the half-lives of the two phases were 0.16 and 1.27 h. Metabolism was the major route of elimination of EMP. It was readily dephosphorylated and oxidized to yield the cytotoxic metabolites estramustine and estromustine. Estromustine was the main metabolite in plasma. When given orally EMP underwent extensive presystemic dephosphorylation, which started in the gastrointestinal tract. The relative bioavailability of estromustine after administration of EMP-capsules was 44%, which reflects incomplete absorption of EMP rather than first-pass metabolism of estromustine. The terminal half-life of estromustine was 10–20 h, which suggests that EMP might be given once or twice a day.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00546718
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  • 9
    Electronic Resource
    Electronic Resource
    Lack of clinically important interaction between erythromycin and theophylline (1984)
    Springer
    European journal of clinical pharmacology 26 (1984), S. 485-489 
    Details
    ISSN: 1432-1041
    Keywords: theophylline ; erythromycin ; interaction ; metabolism ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In 11 healthy volunteers the kinetics of theophylline and the plasma levels and the urinary excretion of its metabolites were studied before and after treatment with erythromycin for 10 days. Theophylline was administered as an intravenous bolus injection (280 mg) followed by a constant intravenous infusion (23.8±4.1 mg/h) for 6 hours. The total clearance of theophylline at steady-state (63.4±9.9 vs 63.8±14.4 ml/min, before vs after erythromycin treatment) and the elimination half-life after cessation of the infusion (6.7±2.6 vs 7.5±1.8 h, before vs after treatment) did not change during the treatment with erythromycin. No difference in the formation of metabolites before and after treatment with erythromycin was detected; the findings in urine were 40.4±5.0 vs 42.1±5.4% 1,3-dimethyluric acid, 29.6±4.6 vs 30.1±5.9% 1-methyluric acid and 13.4±3.5 vs 12.5±2.2% 3-methylxanthine before and after erythromycin treatment, respectively. It is concluded that a clinically relevant interaction between erythromycin and theophylline does not occur.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00542146
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  • 10
    Electronic Resource
    Electronic Resource
    Plasma kinetics of dipyrone metabolites in rapid and slow acetylators (1984)
    Springer
    European journal of clinical pharmacology 27 (1984), S. 453-458 
    Details
    ISSN: 1432-1041
    Keywords: dipyrone ; metabolism ; metabolite pharmacokinetics ; acetylation polymorphism ; healthy volunteers ; dapsone phenotyping
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of the dipyrone metabolites 4-methylaminoantipyrine (MAA), 4-aminoantipyrine (AA), 4-formylaminoantipyrine (FAA) and 4-acetylaminoantipyrine (AAA) were evaluated following the administration of a single oral 1.0 g dose of dipyrone to 23 healthy volunteers. Twelve were slow and 11 were rapid acetylators as previously determined by dapsone phenotyping. For MAA and FAA the mean peak plasma concentrations were 10.5±2.8 µg/ml and 2.1±0.8 µg/ml and the half-lives were 3.3±1.0 and 10.1±1.8 h, respectively. No significant difference was found between rapid and slow acetylators in MAA and FAA kinetics. For AA, the mean peak plasma concentrations were 2.7±0.6 and 1.6±0.7 µg/ml (p〈0.01), the peak times 6.7±2.1 and 3.1±1.1 h (p〈0.01) and the half-lives were 5.5±1.0 and 3.8±1.2 h in slow and rapid acetylators, respectively. For AAA, the mean peak plasma concentrations were 1.6±0.4 and 4.4±1.1 µg/ml (p〈0.01) and the peak time 16.1±5.1 and 10.0±2.6 h (p〈0.01) in slow and rapid acetylators, respectively. There was no difference in the elimination half-life between the two groups (10.6±2.2 h). Thus, it has been demonstrated that the AAA/AA ratio is an indicator of the acetylation phenotype, as it is closely correlated with that determined by dapsone (r=0.895, p〈0.0005).
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00549594
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  • 11
    Electronic Resource
    Electronic Resource
    Enantioselective steady-state kinetics of unbound disopyramide and its dealkylated metabolite in man (1991)
    Springer
    European journal of clinical pharmacology 41 (1991), S. 481-484 
    Details
    ISSN: 1432-1041
    Keywords: Disopyramide ; pharmacokinetics ; protein binding ; enantiomers ; metabolism ; metabolite kinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Disopyramide is provided as a racemic mixture of R and S enantiomers, which have different pharmacodynamic and pharmacokinetic characteristics. Five volunteers were given racemic disopyramide 100 mg and 200 mg t.d.s. in a cross-over design. Plasma and urine concentrations of disopyramide and its active metabolite monodesisopropyl-disopyramide (MND) were determined at steady state by an enantioselective HPLC method. Unbound drug in plasma was measured after ultrafiltration. There was enantioselective clearance of unbound disopyramide (0.39 l.h−1.kg−1 for R-disopyramide and 0.58 l.h−1.kg−1 for S-disopyramide after 100 mg t.d.s.). The enantioselectivity was due to differences in the metabolism of disopyramide to MND and in further non-renal clearance, and the renal clearance of disopyramide was not enantioselective. The in vivo protein binding of disopyramide, which was saturable for both enantiomers, was also enantioselective. The difference in binding of the two enantiomers was explained by a difference in apparent binding capacity rather than in apparent binding affinity. The renal clearance of S-MND was significantly higher than R-MND (0.29 and 0.19 l.h−1.kg−1, respectively, after 100 mg t.d.s.). The renal clearance of MND also showed a tendency to saturation at higher concentrations.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00626374
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  • 12
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of intramuscular nicomorphine and its metabolites in man (1991)
    Springer
    European journal of clinical pharmacology 41 (1991), S. 375-378 
    Details
    ISSN: 1432-1041
    Keywords: Nicomorphine ; 6-nicotinoylmorphine ; morphine ; intramuscular administration ; metabolism ; absorption ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary After i.m. injection nicomorphine is relatively slowly absorbed from the muscular depot and is found in the serum for approximately 1 h. The rate of absorption differs between patients and governs the overall pharmacokinetic profile of the compound. The relative AUCs were nicomorphine 18%, 6-nicotinoylmorphine 17%, and morphine 65%. Nicomorphine and 6-nicotinoylmorphine have significantly higher AUCs after i.m. injection than after i.v. injection, while the AUC of morphine and the total AUC show no difference between the two modes of administration.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00314971
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  • 13
    Electronic Resource
    Electronic Resource
    Effect of a reversible and selective MAO-A inhibitor (cimoxatone) on diurnal variation in plasma prolactin level in man (1984)
    Springer
    European journal of clinical pharmacology 26 (1984), S. 71-77 
    Details
    ISSN: 1432-1041
    Keywords: cimotaxone ; MAO inhibitor ; plasma prolactin ; circadian rhythm ; healthy volunteers ; hypothalamic MAO ; prolactin secretion ; metabolism ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Prolactin (PRL) secretion is stimulated by serotonin (5-HT) and inhibited by dopamine (DA). 5-HT is generally recognized as a substrate for type A monoamine oxidase (MAO), whereas DA is considered as a substrate for either A or B, or both forms of MAO, depending on the species and tissues used. The effect of cimoxatone, a reversible, selective MAO-A inhibitor, on diurnal variation in plasma PRL level was investigated in healthy adults after a single 40 mg oral dose, as an indirect approach to investigating whether DA is preferentially a substrate for Type A or B MAO in man. The circadian rhythm in PRL, stress conditions and diet were taken into account in the present study, which was placebo-controlled. There was a slight but significant reduction in circulating PRL in the six subjects, which persisted for at least 9 h after cimoxatone. However, the duration of the decrease in plasma PRL was shorter than the inhibition of MAO-A. The results are not inconsistent with the presence of both forms of MAO in the human hypothalamus and with DA as a substrate for both forms in this region, if it is assumed that the hypothalamic concentrations of the drug during the period 0–9 hours was sufficiently high to inhibit DA deamination by both forms of MAO.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00546712
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  • 14
    Electronic Resource
    Electronic Resource
    On the role of peroxisomes in the metabolism of lipids — evidence from studies on mammalian tissues in vivo (1984)
    Springer
    Molecular and cellular biochemistry 65 (1984), S. 23-35 
    Details
    ISSN: 1573-4919
    Keywords: fatty acids ; lipids ; metabolism ; oxidation ; peroxisomes ; regulation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Summary Recent investigations into the role of peroxisomes in mammalian lipid metabolism have employed double isotope methodologies to examine the influence of peroxisomal agents on lipid turnover in the liver and extra hepatic tissues of the living animal. The action of these agents, all of which caused extensive changes in the flux of lipid metabolism in the treated animals, may best be viewed in relation to their effects on the common pathway of fatty acid oxidation in peroxisomes. Clofibrate, for example, acts through induction of peroxisomal oxidases and catalase; glycolate and ethanol through activation of this pathway; and aminotriazole and allylisopropylacetamide through inhibition of the catalase step in the sequence. The data from these studies provide support for the concept of an important contributory and regulatory role of peroxisomes in relation to the overall balance of lipid metabolism, and emphasize that these organelles play a significant role in the oxidation of common fatty acids, as well as a potential for the elimination of fatty acids that are poorly oxidized by mitochondria. Additionally, the data raise intriguing questions on the extension of peroxisomal influence to include phospholipid metabolism and the substantial degree of inter-tissue communication which is involved in the balance of lipid metabolism in the whole animal.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00226016
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  • 15
    Electronic Resource
    Electronic Resource
    Metabolism of uscharidin, a milkweed cardenolide, by tissue homogenates of monarch butterfly larvae,Danaus plexippus L. (1984)
    Springer
    Journal of chemical ecology 10 (1984), S. 945-956 
    Details
    ISSN: 1573-1561
    Keywords: Cardenolide ; uscharidin ; metabolism ; monarch butterfly ; Danaus plexippus ; Lepidoptera ; Danaidae ; milkweed ; Asclepias ; N-demethylation ; mixed function oxidase ; monooxygenase
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract Midgut and fat body homogenates of monarch butterfly larvae,Danaus plexippus L. (Lepidoptera:Danaidae), were examined for microsomal monooxygenase activity usingp-chloro-N-methylanilineN-demethylation and for the ability to metabolize a milkweed (Asclepias spp.) cardenolide (C23 steroid glycoside), uscharidin. All homogenates tested had bothN-demethylation and uscharidin biotransformation activities. Both transformations required NADPH. The monooxygenase inhibitors sesamex, SKF525A, and carbon monoxide inhibitedN-demethylation but not uscharidin biotransformation. Subsequent subcellular fractionation revealed the uscharidin biotransformation occurs in the soluble fraction and not the microsomal fraction, whileN-demethylation occurs in the microsomal fraction and not the soluble fraction. The larval NADPH-dependent microsomal monooxygenase apparently is not involved in the metabolism of uscharidin.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00987975
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  • 16
    Electronic Resource
    Electronic Resource
    The key role of hydroxylation for the cytostatic activity and selectivity of cyclophosphamide (1984)
    Springer
    Investigational new drugs 2 (1984), S. 131-132 
    Details
    ISSN: 1573-0646
    Keywords: cyclophosphamide ; metabolism ; ASTA Z 7557 ; 4-hydroxy-cyclophosphamide
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The “pro-drug” cyclophosphamide (CP) is activated by liver “mixed function” hydroxylases to 4-hydroxy-cyclophosphamide (4-OH-CP), which represents the cytostatically active principle. Since the primary metabolite 4-OH-CP retains all the specific pharmacological properties of the parent compound without the need of metabolic activation, it constituted the basic principle and rationale for further drug development. Due to its chemical instability, 4-OH-CP had to be stabilized through appropriate substitutions at the 4-position of the oxazaphosphorine ring. ASTA Z 7557, in which the side chain is a 2-mercapto-ethanesulfonate, represents the prototype of this new class of oxazaphosphorines.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00232341
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  • 17
    Electronic Resource
    Electronic Resource
    Differences in N-acetylation of the experimental antitumor agent batracylin in the mouse and the rat (1991)
    Springer
    Investigational new drugs 9 (1991), S. 219-225 
    Details
    ISSN: 1573-0646
    Keywords: batracylin ; preclinical pharmacology ; metabolism ; N-acetylation ; mice ; rats
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Batracylin (NSC-320846) is a quinalzolineone recently evaluated as a potential antitumor agent by the National Cancer Institute. The analog was active against a number of murine tumors, including colon adenocarcinoma 38 and multidrug resistant sublines of P-388 leukemia. Preclinical toxicity studies revealed that batracylin was much more toxic when administered orally to rats than to mice. The combined sex LD10 in mice was 5,655 mg/m2 while 576 mg/m2 was lethal to all rats treated at that dose. We determined that following oral administration of batracylin, systemic exposure of parent drug to the rat was only 14.9% of that to the mouse. It was subsequently noted that systemic exposure of a relatively non-polar metabolite was approximately 9 times greater in the rat than in the mouse. The metabolite was identified as N-acetylbatracylin by TLC, HPLC and mass spectral analyses. Observations by the National Cancer Institute that N-acetylbatracylin was not toxic following oral administration to mice or rats prompted evaluation of systemic exposure following oral administration to rats. Following oral administration of N-acetylbatracylin to rats, systemic exposure was almost nil. Indeed, exposure of rats to N-acetylbatracylin was several orders of magnitude greater following oral administration of six-fold lower doses of the parent drug, batracylin. Thus, N-acetylation may play a role in the toxicity of batracylin despite the lack of toxicity observed following oral administration of N-acetylbatracylin. In addition, further metabolism of the N-acetyl conjugate, analogous to that of other aromataic amines, may be involved in the pharmacology of batracylin and similar analogs.
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    URL: http://dx.doi.org/10.1007/BF00176974
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    Growth and metabolism of human tumor kidney cells on galactose and glucose (1991)
    Springer
    Cytotechnology 7 (1991), S. 7-13 
    Details
    ISSN: 1573-0778
    Keywords: galactose ; glucose ; metabolism ; microcarrier ; reactor ; tumor cell
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Process Engineering, Biotechnology, Nutrition Technology
    Notes: Abstract The culture kinetics of human tumor kidney cells (TCL 598) grown on microcarriers are compared with media initially supplemented with either glucose alone or a mixture of galactose and glucose. Growth rates and maximal cell densities are similar, but cellular death is much slower in galactose than in glucose. Galactose is metabolized at a much slower specific rate than glucose. Cells grown in the galactose medium show a different pattern of lactate and pyruvate metabolism compared to cells grown in the glucose medium. Growth with galactose also favours oxidation of glutamine to alanine.
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    URL: http://dx.doi.org/10.1007/BF00135633
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  • 19
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    Inhibitory action of antiarrhythmic phenothiazine drugs ethmozine and its diethylamino analog on platelet aggregation and metabolism of endogenous arachidonic acid (1984)
    Springer
    Bulletin of experimental biology and medicine 97 (1984), S. 74-77 
    Details
    ISSN: 1573-8221
    Keywords: antiarrhythmic drugs ; metabolism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00830249
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    Effect of phenothiazines on Ca-ATPase of the sarcoplasmic reticulum in rabbit skeletal muscles (1984)
    Springer
    Bulletin of experimental biology and medicine 97 (1984), S. 441-443 
    Details
    ISSN: 1573-8221
    Keywords: phenothiazine ; skeletal muscle ; Ca-ATPase ; metabolism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00829653
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  • 21
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    Effect of propranolol on metabolic processes in blood and lymph in acute myocardial infarction (1991)
    Springer
    Bulletin of experimental biology and medicine 111 (1991), S. 24-27 
    Details
    ISSN: 1573-8221
    Keywords: metabolism ; blood ; lymph ; propranolol ; myocardial infarction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00841230
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  • 22
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    Induction of quinidine metabolism and plasma protein binding by phenobarbital in dogs (1984)
    Springer
    Journal of pharmacokinetics and pharmacodynamics 12 (1984), S. 495-515 
    Details
    ISSN: 1573-8744
    Keywords: quinidine ; phenobarbital ; induction ; protein binding ; metabolism ; dogs
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Two porta-caval transposed mongrel dogs were studied for phenobarbital (PB) induction of quinidine disposition after separate quinidine infusions via normal intravenous route and via portal vein. The plasma concentrations of quinidine and of three metabolites measured (3-OH quinidine, quinidine N-oxide, quinidine 10,11-dihydrodiol) were quite similar between i.v. and portal vein infusions, suggesting that the liver extraction ratio for quinidine in dogs is very low. After PB pretreatment plasma quinidine concentrations at the end of a 10 hr infusion increased about two-fold while the half-life decreased from a control value of about 16 hr to 6 hr. Plasma concentrations of the three major metabolites measured were also increased following PB treatment. Plasma protein binding for quinidine and two of its three measured metabolites (3-hydroxy quinidine and quinidine N-oxide) were increased after PB treatment. Pharmacokinetic analysis of the data showed a decrease in steady-state volume of distribution (Vdss)of quinidine from an average value of 153 L to 54 L after PB treatment, while the total clearance did not change (6.6 vs. 5.6L/hr). This decrease in Vdss could be explained by an increase in plasma protein binding of quinidine after PB treatment. The unbound nonrenal clearance of quinidine was induced by PB treatment. The decrease in fraction free in plasma and increase in unbound nonrenal (hence total) clearance resulted in little or no change in total plasma clearance for quinidine. The formation rate constants calculated for two quinidine metabolites, 3-hydroxy quinidine and quinidine N-oxide, were increased after PB treatment, suggesting an induction in these two metabolic pathways. Only quinidine 10,11-dihydrodiol was found in the bile after quinidine infusion, and the biliary clearance of this metabolite was also induced after PB treatment.
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    URL: http://dx.doi.org/10.1007/BF01060128
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  • 23
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    A Comparison of Peptidase Activities and Peptide Metabolism in Cultured Mouse Keratinocytes and Neonatal Mouse Epidermis (1991)
    Springer
    Pharmaceutical research 8 (1991), S. 70-75 
    Details
    ISSN: 1573-904X
    Keywords: mouse keratinocytes ; mouse epidermis ; aminopeptidases ; peptidases ; metabolism ; Leu-enkephalin ; liquid chromatography
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract One of the barriers to transdermal delivery of peptides is the metabolic activity of the epidermis. To define this metabolic activity, aminopeptidase activity and Leu-enkephalin metabolism were measured in the epidermis obtained from neonatal mouse skin and in cultured mouse keratinocytes. Aminopeptidase activity was measured fluorometrically using leucine, tyrosine, lysine, and aspartic acid derivatives of β-naphthylamine as substrates. Similarities in substrate kinetic values (K m and V max) and substrate specificity of the enzyme(s) in homogenates prepared from neonatal mouse skin epidermis and cultured mouse keratinocytes strongly suggest that the keratinocytes in culture express the same aminopeptidase(s) with the same relative activity as in neonatal skin. The K m and V max values for aminopeptidase(s) with different substrates in epidermis homogenates are as follows: leucine β-naphthylamide (11 µM and 38 nmol · min−1 · mg−1), tyrosine (β-naphthylamide (21 µM and 18 nmol · min−1 · mg−1), and lysine β-naphthylamide (11 µM and 35 nmol · min−1 · mg−1). Aspartic acid β-naphthylamide and glutamic acid β-naphthylamide were not hydrolyzed by these homogenates at pH 7.4 (37°C). Leu-enkephalin hydrolysis by the homogenates from cultured mouse keratinocytes and neonatal mouse epidermic gave similar K m (32 and 24 µM), V max (9.77 and 7.55 nmol · min−1 · mg−1) and K i (223 and 194 µM) values. In addition, the cellular homogenates gave similar metabolite profiles for Leu-enkephalin.
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    URL: http://dx.doi.org/10.1023/A:1015882323677
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  • 24
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    14C-Isomazole Disposition in Man After Oral Administration (1991)
    Springer
    Pharmaceutical research 8 (1991), S. 1413-1417 
    Details
    ISSN: 1573-904X
    Keywords: isomazole ; inotropic agent ; pharmacokinetics ; metabolism ; disposition ; humans
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract A 50-mg dose containing 50 µCi 14C-isomazole was administered orally to five healthy male volunteers. Blood, plasma, urine, feces, and saliva were collected and measured for total 14C; in addition, all collections except feces were measured for parent drug (ISO) and three metabolites: hydroxyisomazole (OHISO) and sulfone (SULF) and hydroxysulfone (OHSULF) analogues. Urine and fecal recoveries accounted for 97.0% of the drug administered, with 62.6% excreted in urine and 32.4% in feces. Only 47% of the drug recovered in urine could be identified, with ISO the largest constituent. Total plasma 14C peaked at 1.5 hr, indicating rapid absorption, and produced a mean half-life of 3.7 hr. This was similar to the total 14C half-life found in blood (3.1 hr) but longer than in red blood cells (1.8 hr) or saliva (1.4 hr), suggesting that different ISO-related compounds contributed to the results found in each fluid or tissue. An unidentified metabolite(s) composed a large portion of circulating plasma 14C and produced the longer half-life encountered in plasma. ISO exhibited a short half-life (1.35 hr), a high oral clearance (ClS/F; 24.2 ml/min/kg), and some extravascular distribution (Vβ; 3.07 L/kg). Total 14C in red blood cells and saliva related very well to plasma ISO disposition, suggesting preferential distribution of parent drug across cellular membranes. The estimated RBC:plasma ISO ratio (1.79) confirmed this hypothesis. Saliva may be used as a noninvasive means to monitor ISO disposition.
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    URL: http://dx.doi.org/10.1023/A:1015857324838
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    Variable Glyceryl Dinitrate Formation Following Infusions of Glyceryl Trinitrate at Different Vascular Sites in the Rat (1991)
    Springer
    Pharmaceutical research 8 (1991), S. 877-882 
    Details
    ISSN: 1573-904X
    Keywords: nitroglycerin ; glyceryl ; nitrate ; clearance ; metabolism ; uptake
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The availability of glyceryl trinitrate (GTN) and the differential formation of dinitrate metabolites (GDNs) in various organs as a function of routes of administration were investigated in the rat. GTN was infused at 2.0 µg/min via the left femoral vein (LFV), left external jugular vein (LJV), left femoral artery (LFA), and hepatic portal vein (HPV). Blood concentrations of GTN and GDNs were measured in femoral arterial samples. Different infusions yielded GTN steady-state concentrations in the following rank order: LJV ≥ LFV 〉 LFA ≥ HPV. Furthermore, the GDN formation ratios (1,2-GDN/1,3-GDN) are different: LFV ≥ LJV 〉 LFA 〉 HPV. The availabilities of GTN through the leg, vein, and liver were derived. GTN is significantly extracted and metabolized in these organs, and the leg and the vein prefer 1,2-GDN formation, while the liver forms 1,3-GDN predominantly.
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    URL: http://dx.doi.org/10.1023/A:1015851412175
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    The Pharmacokinetics and Metabolism of Human Relaxins in Rhesus Monkeys (1991)
    Springer
    Pharmaceutical research 8 (1991), S. 1032-1038 
    Details
    ISSN: 1573-904X
    Keywords: relaxin ; pharmacokinetics ; metabolism ; protein ; mass spectrometry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Two forms of chemically synthesized human relaxin (hRlx and hRlx-2) were administered as 88 µg/kg intravenous bolus doses to pregnant and nonpregnant rhesus monkeys. No significant differences in pharmacokinetics were observed between pregnant and nonpregnant animals for either form of relaxin; however, clearance of hRlx (3.1–3.4 ml/min/kg) was significantly slower than clearance of hRlx-2 (6.2–6.5 ml/min/kg) in both pregnant and nonpregnant animals. Although the terminal half-lives for hRlx and hRlx-2 were similar (148–157 min), the initial and steady-state volumes of distribution were somewhat larger for hRlx-2 (71–85 and 398–418 ml/kg, respectively) than for hRlx (61–65 and 294–319 ml/kg, respectively). The metabolism of hRlx-2 was also investigated in pregnant and non-pregnant rhesus monkeys after iv bolus (0.44 mg/kg) or 60-min infusion (1.1 mg/kg) administration. Fast atom bombardment mass spectral analysis of the relaxin immunoreactivity isolated from the plasma indicated that hRlx-2 was partially degraded by removal of amino acids from the C terminus of the B chain. The percentage of intact material declined over a 60-min time course. At 60 min post-dose, intact hRlx-2 was ∼46–64% of the detected material. Degraded forms representing loss of one and four amino acids (hRlx) from the C terminus of the B chain were ∼11–13 and ∼19–34% of the detectable material, respectively.
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    URL: http://dx.doi.org/10.1023/A:1015861108966
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    Drug Metabolism and Laboratory Anesthetic Protocols in the Rat: Examination of Antipyrine Pharmacokinetics (1991)
    Springer
    Pharmaceutical research 8 (1991), S. 544-546 
    Details
    ISSN: 1573-904X
    Keywords: anesthesia ; antipyrine ; metabolism ; pharmacokinetics ; rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1015827917684
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  • 28
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    Fate of photosensitizing furanocoumarins in tolerant and sensitive insects (1984)
    Springer
    Journal of chemical ecology 10 (1984), S. 893-911 
    Details
    ISSN: 1573-1561
    Keywords: Xanthotoxin ; psoralen ; isopsoralen ; furanocoumarin ; Papilio polyxenes ; Lepidoptera ; Papilionidae ; Spodoptera frugiperda ; Noctuidae ; metabolism ; detoxification ; tolerance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract The fate of [14C]xanthotoxin (8-methoxypsoralen) was studied in larvae of insect species that are tolerant (Papilio polyxenes Stoll) or sensitive (Spodoptera frugiperda J.E. Smith) to the phototoxic effects of photosensitizing psoralens. Both insects metabolize xanthotoxin by oxidative cleavage of the furan ring, but the detoxification occurs at a much more rapid rate inP. polyxenes in which 〉95% of an oral 5 μg/g xanthotoxin dose is metabolized within 1.5 hr after treatment. The detoxification of psoralens byP. polyxenes appears to occur primarily in the midgut tissue prior to absorption, with the result that the intact phototoxin does not reach appreciable levels in body tissues. Studies with an angular furanocoumarin indicated that isopsoralens are metabolized byP. polyxenes at a somewhat slower rate than observed for psoralens; however, a reduced rate of metabolic detoxification of isopsoralens probably does not explain the fact that psoralen tolerance inP. polyxenes does not extend to the isopsoralen series.
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    URL: http://dx.doi.org/10.1007/BF00987971
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    Cerebrovascular lesion caused by activation of platelets and leukocytes and their correction by neurotropin (1991)
    Springer
    Bulletin of experimental biology and medicine 112 (1991), S. 1448-1450 
    Details
    ISSN: 1573-8221
    Keywords: neurotropin ; platelets ; neutrophils ; aggregation ; metabolism ; brain tissue
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00841368
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    Specificity of the toxic genetic action of carcinogenic aromatic compounds on mus-mutant strains ofDrosophila (1991)
    Springer
    Bulletin of experimental biology and medicine 112 (1991), S. 1631-1633 
    Details
    ISSN: 1573-8221
    Keywords: Drosophila ; genetic toxicity ; specificity ; metabolism ; precarcinogens
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00840433
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    EEG changes in animals with neurosis as a correlate of disturbances of brain metabolism (1984)
    Springer
    Bulletin of experimental biology and medicine 97 (1984), S. 552-555 
    Details
    ISSN: 1573-8221
    Keywords: neurosis ; electroencephalogram ; brain ; metabolism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00808227
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    Effect of antisynaptosomal antibodies on synaptosomal protein metabolism (1984)
    Springer
    Bulletin of experimental biology and medicine 98 (1984), S. 1188-1189 
    Details
    ISSN: 1573-8221
    Keywords: antibodies ; brain ; synapse ; proteins ; metabolism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00804292
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    Effect of riboxine on myocardial metabolism in high-altitude hypoxia (1984)
    Springer
    Bulletin of experimental biology and medicine 97 (1984), S. 503-505 
    Details
    ISSN: 1573-8221
    Keywords: riboxine ; hypoxia ; metabolism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00829674
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