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  • 1
    Electronic Resource
    Electronic Resource
    Distribution and effects on cytochrome P450 system of two hexachlorobiphenyl isomers in the rat (1991)
    Springer
    Archives of toxicology 65 (1991), S. 661-665 
    Details
    ISSN: 1432-0738
    Keywords: Polychlorinated biphenyls ; 2,2′,3,3′,6,6′-hexachlorobiphenyl ; 2,2′,4,4′,5,5′-hexachlorobiphenyl ; Cytochrome P450 isoenzymes ; Enzyme induction ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Tissue distribution and effects induced by 2,2′,4,4′,5,5′-hexachlorobiphenyl (245-HCB) on cytochrome P450 isozymes were compared with those of 2,2′,3,3′,6,6′-hexachlorobiphenyl (236-HCB). Male Wistar rats were given a single intragastric dose (23 mg/kg body wt) of either isomer, and killed after 72 h. At termination the tissue concentrations of 245-HCB were considerably higher than those of 236-HCB, suggesting a more effective metabolism of the latter. The binding affinity of 236-HCB to cytochrome P450 was higher and the magnitude of binding greater than of 245-HCB. 245-HCB-treatment elevated the hepatic concentration of cytochrome P450 and also the activities of 7-pentoxyresorufin O-depentylase (50-fold), aniline p-hydroxylase (2-fold) and 7-ethoxycoumarin O-deethylase (2-fold), a response typical of phenobarbital-type inducers. In the Western immunoblot of liver microsomes from 245-HCB treated rats, an increased amount of P450IIB1/2 was detected by a monoclonal antibody 2-66-3, which specifically detects phenobarbital inducible isoenzymes. The minimum molecular mass of the P450 isozyme induced was 52 kDa. After 236-HCB administration, a weak inducing effect was observed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02098033
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  • 2
    Electronic Resource
    Electronic Resource
    Environmental influences on human foetal and placental xenobiotic metabolism (1980)
    Springer
    European journal of clinical pharmacology 18 (1980), S. 17-24 
    Details
    ISSN: 1432-1041
    Keywords: foetus ; xenobiotic metabolism ; placenta ; environment ; induction ; ontogenesis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The human foetus is more capable of metabolizing xenobiotics than foetuses of common laboratory animal species. However, xenobiotic metabolism in animal foetuses is inducible by the exposure of the mother to various inducers during late pregnancy. Xenobiotic metabolism in neonates is more easily inducible than in foetal animals. With respect to the human foetus at mid-pregnancy, the hepatic enzyme systems do not seem to be readily inducible by exogenous inducers, whereas the placental monooxygenase system is almost totally dependent on maternal cigarette smoking. In the human newborn, indirect evidence points to the possibility of induction by potential inducers. The ontogenetic development of xenobiotic metabolism is probably regulated by endogenous hormones. It is possible that environmental factors may affect these normal regulatory and “imprinting” phenomena and thus lead to permanent disturbances in xenobiotic metabolism.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00561474
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  • 3
    Electronic Resource
    Electronic Resource
    Effect of cimetidine on microsomal drug metabolism in man (1980)
    Springer
    European journal of clinical pharmacology 18 (1980), S. 185-187 
    Details
    ISSN: 1432-1041
    Keywords: cimetidine ; microsomal drug metabolism ; man ; interaction ; liver microsomes ; antipyrine kinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effect of cimetidine on human microsomal drug metabolism was studied. In five of six healthy volunteers therapeutic doses of cimetidine prolonged the half-life of antipyrine (range 12–37%; p〈0.05). Its clearance was decreased in five subjects (range 2–18%) and was increased in one subject (15%), the changes not being statistically significant. The volume of distribution increased on average by about 14% (range 9–19%; p〈0.001). Cimetidine in vitro inhibited the hydroxylation of benzo(a)pyrene and coumarin, as well as the O-deethylation of 7-ethoxycoumarin, by homogenised liver biopsies. The in vitro studies suggest that the effect of cimetidine on antipyrine elimination is due to inhibition of microsomal drug metabolism, which may prove an important drug interaction.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00561588
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  • 4
    Electronic Resource
    Electronic Resource
    Interindividual variability of coumarin 7-hydroxylation in a Turkish population (1994)
    Springer
    European journal of clinical pharmacology 47 (1994), S. 315-318 
    Details
    ISSN: 1432-1041
    Keywords: Coumarin ; Coumarin 7-hydroxylation ; interindividual variability ; polymorphism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract One hundred healthy Turkish volunteers (70 male, 30 female) aged from 19 to 56 years were given 5 mg coumarin p.o. after an overnight fast. Urine samples were collected before and 2, 4 and 8 h after drug administration. The extent and rate of formation of 7-OH-coumarin (7OHC) was determined by the urinary excretion of the metabolite as measured with the fluorometric method. On average, 80% of 7OHC formed was excreted in 2 h. The total amount of 7OHC formed was 59.8% (21.5%) (mean and SD, n=100, range 17–100%) of the given dose. The percentage of 7OHC excreted during the first 2 h compared with the 7OHC excretion at 8 h was a constant and stable individual characteristic for the rate of the formation of 7OHC (‘2 h coumarin test’). Although four individuals had relatively slow coumarin test values (34–40%), no clear-cut polymorphism in the rate of 7OHC formation was found. However, 7OHC formation was lower in males and in cigarette smokers.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00191161
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  • 5
    Electronic Resource
    Electronic Resource
    Placental transfer and hormonal effects of metoclopramide (1983)
    Springer
    European journal of clinical pharmacology 24 (1983), S. 345-348 
    Details
    ISSN: 1432-1041
    Keywords: metoclopramide ; placental transfer ; prolactin ; maternal blood level ; fetal blood level ; amniotic fluid level ; plasma half-life ; plasma TSH ; plasma oestradiol
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In order to study the transplacental transfer of metoclopramide, and its endocrine effects, measurements were made of its concentration in maternal and fetal blood, and in the amniotic fluid, together with maternal and fetal plasma concentrations of prolactin, TSH and oestradiol, during delivery by elective Caesarean section. The drug, 10 mg, was injected i.m. 12 and 2 h and just before the onset of anaesthesia. Metoclopramide was detectable in all the umbilical arterial and venous and amniotic fluid samples, in mean concentrations of 50, 63 and 75 ng/ml, respectively. The mean ratio between the umbilical venous and maternal plasma concentrations was 0.63. Accurate maternal plasma half-lives could not be established, but they must have averaged 2 to 4 h. The high amniotic fluid concentrations and relatively high umbilical venous and arterial concentrations soon after administration suggest that metoclopramide equilibrates relatively rapidly between the mother and fetus. Metoclopramide raised the maternal plasma prolactin levels from 315±128 ng/ml (SD) before therapy to 357±112 ng/ml at the time birth. No statistically significant difference in cord arterial or venous plasma prolactin levels was seen between the control and metoclopramide-treated groups. Metoclopramide did not affect maternal plasma TSH or oestradiol levels. The only change was a slight but significant increase in TSH level in cord blood taken from the umbilical artery after metoclopramide treatment.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00610052
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  • 6
    Electronic Resource
    Electronic Resource
    Placental transfer of clenbuterol early in human pregnancy (1982)
    Springer
    European journal of clinical pharmacology 22 (1982), S. 403-406 
    Details
    ISSN: 1432-1041
    Keywords: clenbuterol ; pregnancy ; placental transfer ; fetal concentration ; placental concentration ; amniotic fluid concentration ; maternal plasma level ; maternal-fetal concentration ratio
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary After administration of clenbuterol 80 µg p.o., a β-adrenoceptor agonist, the concentrations of (14C-labelled)clenbuterol in fetus, placenta and maternal plasma in 9 patients at 9–12 weeks gestation were measured during therapeutic abortion. The time interval between the administration and abortion ranged from 120 to 280 min. The mean concentrations of clenbuterol in maternal plasma, fetus and placenta were 0.37 (range 0.22–0.56), 0.32 (0.14–0.48) and 0.91 (0.12–1.73) ng equivalents per ml or per gram of tissue wet weight. The mean concentration ratio of clenbuterol between fetus and maternal plasma was 0.84 (6 cases); it did not vary with time. The concentration of clenbuterol in three amniotic fluid samples ranged from 0.06 to 0.18 ng/ml (mean 0.11). Maternal plasma concentrations showed wide variability of the pharmacokinetic phase at the time of abortion. The studies indicate that clenbuterol crosses the placenta early in human pregnancy and that it accumulates in the placenta.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00542542
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  • 7
    Electronic Resource
    Electronic Resource
    Metoclopramide and breast feeding: Transfer into milk and the newborn (1983)
    Springer
    European journal of clinical pharmacology 25 (1983), S. 819-823 
    Details
    ISSN: 1432-1041
    Keywords: metoclopramide ; breast milk level ; transfer into milk ; prolactin ; thyrotrophin ; maternal blood level ; newborn blood level
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics and endocrinological effects of metoclopramide were investigated in 5 mothers with deficient lactation and in their children soon after delivery. In addition, the transfer of metoclopramide into breast milk was evaluated in 18 mothers during the 8th to 12th puerperal weeks. Metoclopramide was detected in all the milk samples studied, generally at a higher concentration than in maternal plasma. Metoclopramide was found in plasma from only 1 of the 5 neonates studied. Exposure of the child to metoclopramide, estimated by multiplying the daily breast milk volume by the concentration of metoclopramide in the milk, ranged from 6 to 24 µg/kg/day for the 5 children in the early puerperium to 1 to 13 µg/kg/day for the 18 children during the late puerperium. These quantities are considerably less than the therapeutic dose of 500 µg/kg/day recommended for children. However, the plasma concentration of prolactin in 4 out of 7 neonates sampled taken during administration of metoclopramide to the mother were higher than the highest plasma prolactin level in children of same age of untreated mothers. The plasma concentration of thyrotrophin in the newborns remained within the normal range.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00542527
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  • 8
    Electronic Resource
    Electronic Resource
    Coumarin 7-hydroxylation in long-term adherents of a strict uncooked vegan diet (1996)
    Springer
    European journal of clinical pharmacology 50 (1996), S. 133-137 
    Details
    ISSN: 1432-1041
    Keywords: Key words Coumarin ; Coumarin 7-hydroxylation ; Vegan diet ; Biotransformation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Objective: Coumarin 7-hydroxylation was investigated in 21 Finnish vegans (20 females, one male) consuming a strict, uncooked vegan diet (“living food diet”) and in their matched omnivorous controls, by means of an in vivo coumarin test. Method: A capsule containing 5 mg of coumarin (Venalot®) was taken after an overnight fast, and urine samples were collected before and 2, 4 and 6 h after the drug administration. The extent and rate of urinary excretion of 7-hydroxycoumarin was determined using HPLC. Results: The total urinary excretion of 7-hydroxycoumarin during 6 h was 58 (range 23–85) and 64 (range 39–92)% of the administred dose in the vegan and control groups. The coumarin index (excretion of 7-hydroxycoumarin during the first 2 h as percentage of total excretion) was 72% in the vegan and 78% in the control groups. A negative correlation was observed between the coumarin index and the consumption of wheatgrass juice by the vegans (r = −0.60, P 〈 0.01, n = 21). Proportion of slow hydroxylators (excreting 7-hydroxycoumarin after 4 h) was not statistically different between the groups (5/21 in the vegans vs 8/20 in the controls). Conclusion: According to the present study, the clearly different dietary patterns and nutrient intakes between the vegans and the omnivores resulted in similar extent and rate of 7-hydroxycoumarin formation, indicating only a minor effect on coumarin hydroxylase (CYP2A6) activity by the plant substances in the uncooked vegan diet.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002280050081
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  • 9
    Electronic Resource
    Electronic Resource
    Serum zinc and serum copper and indices of drug metabolism in alcoholics (1977)
    Springer
    European journal of clinical pharmacology 12 (1977), S. 147-151 
    Details
    ISSN: 1432-1041
    Keywords: Serum zinc ; serum copper ; drug metabolism ; antipyrine ; cytochrome P-450 ; alcoholism ; liver biopsy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Serum zinc and copper levels were studied in relation to in vitro and in vivo drug metabolism in 25 alcoholics, in whom various diseases of the liver had been diagnosed by histology. Serum zinc was elevated in alcoholics with normal or fatty liver and was low in those with alcoholic hepatitis or cirrhosis. There was a significant positive correlation between serum zinc and cytochrome P-450 content of liver biopsies. The relationship between zinc and antipyrine half-life was significant and non-linear. Serum copper level was elevated in all the alcoholics and no significant relationship could be found between copper and drug metabolism in alcoholics. The findings suggest parallelism between changes in serum zinc and indices of drug metabolism in alcoholics.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00645136
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  • 10
    Electronic Resource
    Electronic Resource
    Serum sex hormone levels after replacing carbamazepine with oxcarbazepine (1995)
    Springer
    European journal of clinical pharmacology 47 (1995), S. 461-464 
    Details
    ISSN: 1432-1041
    Keywords: Carbamazepine ; Oxcarbazepine ; Liver enzyme induction ; sex hormones ; sex hormone binding globulin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract The function of the hepatic P450 enzyme system was evaluated by measuring the kinetics of antipyrine and serum sex hormone levels were determined in 12 male patients with epilepsy during carbamazepine medication, and two and six months after changing their medication to oxcarbazepine. Antipyrine t1/2 increased and antipyrine CL decreased after the change reflecting normalisation of the liver P450 enzyme system function. Serum sex hormone binding globulin levels decreased, and serum dehydroepiandrosterone sulphate increased after the change. The results show that the carbamazepine-associated induction of the liver P450 enzyme system and changes in serum sex hormone balance can be avoided by replacing carbamazepine with oxcarbazepine.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00196862
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