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  • phenobarbital  (5)
  • Springer  (5)
  • 1980-1984  (5)
  • 1970-1974
  • 1920-1924
  • 1980  (5)
  • 1971
Collection
Publisher
  • Springer  (5)
Years
  • 1980-1984  (5)
  • 1970-1974
  • 1920-1924
Year
  • 1
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 17 (1980), S. 197-202 
    ISSN: 1432-1041
    Keywords: hexobarbital ; cholestasis ; phenobarbital ; rifampicin ; phenytonin ; pharmackoinetics ; drug metabolism ; induction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of intravenously infused hexobarbital was studied in 10 patients with intrahepatic cholestasis and in 9 with extrahepatic biliary obstruction. The results were compared with those obtained in 16 healthy young volunteers and 5 older patients with normal liver function. After infusion, the plasma concentrations showed a rapid initial decline (α-phase) and subsequently a slower decrease (β-phase). The half-life of a latter phase was 323±84 min in the healthy group, 357±151 min in the patients with intrahepatic cholestasis and 344±115 min in the group with biliary obstruction; the clearances were 3.41±0.90, 4.08±1.95 and 3.81±1.97 ml×min−1×kg−1, respectively. The differences were not statistically significant. The mean volume of the central compartment of distribution and the steady state volume of distribution were not significantly different. In two patients hexobarbital clearance during cholestasis was greater than after it had subsided. After treatment of 11 patients with cholestasis with drug metabolism-inducing agents (phenobarbital, rifampicin or phenytoin), the half-life of hexobarbital was significantly shortened and the mean value of hexobarbital clearance was more than doubled.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 18 (1980), S. 95-104 
    ISSN: 1432-1041
    Keywords: corticosteroids ; progestins ; betamethasone ; phenobarbital ; amniotic fluid ; fetoplacental unit
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Corticosteroids (CS) are known to be essential for fetal organ maturation and seem to play an important role in both the initiation of parturition and the postnatal adaptation of the human neonate. Pharmacologically, CS are widely used for enhancing fetal lung maturation prior to premature delivery. However, knowledge of endogenous CS and precursor levels throughout fetal and perinatal life and their response to exogenous CS is limited. Therefore, using automated liquid column chromatography plus specific radioimmunoassays, unconjugated aldosterone (Aldo), corticosterone (B), 11-deoxycorticosterone (DOC), progesterone (P), 17-hydroxyprogesterone (17-OHP), 11-deoxycortisol (S), cortisol (F) and cortisone (E) were simultaneously followed in 70 amniotic fluid (AF) control samples throughout pregnancy, and in cord and neonatal plasma longitudinally during the first week of life. From 14 to 38 weeks, AF levels of all measured steroids except E rose by 2 to 12-fold on the average (allP〈0.001) but declined at term. E increased until 31–35 weeks (P〈0.01), then remained almost constant until term. Cord levels of all steroids were substantially higher than those found in AF at term. While levels of the placentally derived steroids P, 17-OHP, DOC and E dropped sharply after birth by several orders of magnitude (P≪0.01) showing typical disappearance curves, the biologically most potent CS Aldo and F rose even further immediately after birth. Whereas Aldo levels declined from maxima about 100 times above normal adult levels at 6 h by almost 3-fold until day 7 (P〈0.01), F (and also B) fluctuated considerably resembling a damped oscillation and, by day 7, reached mean levels less than half of those seen in later childhood. After betamethasone treatment of the mother, neonatal levels of Aldo and F were suppressed to 24–69% of normal until day 9, whereas those of the other steroids (except E) returned to normal during the first hours of life. Phenobarbital (PB) therapy of the mother led to decreased steroid levels in maternal and umbilical venous plasma at term, while umbilical arterial CS levels, notably those of Aldo and F (P〈0.02), were increased when compared with untreated controls, indicating a stimulation of the most potent CS in the fetus after PB. The significance of the findings in view of fetoplacental function and fetal organ maturation is briefly discussed.
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 18 (1980), S. 255-261 
    ISSN: 1432-1041
    Keywords: D-glucaric acid ; renal insufficiency ; phenobarbital ; dipyrone ; cortisol ; enzyme induction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The urinary excretion rate ofD-glucaric acid, an in vivo parameter of the activity of drug metabolizing enzymes, has been determined in patients with chronic renal insufficiency (glomerular filtration rate 4.5–80 ml/min/1.73 m2). The mean value of 22.3 µmoles/d (SD 7.2; n 28) was almost identical to that of healthy controls (22.1 µmoles/d, SD 7.3; n 22). Thus, no inhibitory or enhancing effect of renal insufficiency could be detected. The ability of this parameter to indicate alterations in the activity of hepatic drug metabolism, even in patients with renal insufficiency, was demonstrated by the increased excretion rate of glucaric acid (107 µmoles/d, SD 43.5; n 8; p〈0.001) after treatment for 7 days with the enzyme inducer phenobarbital. No significant correlation was found between glucaric acid excretion and sex, age, body weight or body surface in 50 patients. Glucaric acid excretion, therefore, should not be related to the creatinine content of urine samples, since creatinine excretion decreases with severity of renal insufficiency and varies with sex, age, body weight and many other conditions. A single dose of dipyrone (Novalgin®), a further in vivo indicator of drug metabolism, increased glucaric acid excretion on the same day, but no interference was found after a single dose of cortisol.
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  • 4
    ISSN: 1432-1041
    Keywords: primidone ; phenobarbital ; placental transfer ; PEMA ; neonatal metabolism ; aminopyrine demethylation ; renal clearance ; breast milk ; withdrawal symptoms ; GC-MS analysis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The placental transfer of primidone and its metabolites phenobarbital, phenylethylmalondiamide (PEMA) and p-hydroxyphenobarbital (free and conjugated) has been investigated at birth in 14 epileptic women who had been treated with primidone throughout pregnancy. All drugs studied were found in similar concentrations in maternal and cord blood. In seven of the newborns the pharmacokinetics of these drugs were studied during the first postnatal weeks. Primidone and phenobarbital were eliminated with mean half-lives of 23±10 h and 113±40 h, respectively, PEMA with 35±6 h. In some neonates the serum concentrations of phenobarbital and PEMA increased during the first few days due to their formation by neonatal primidone metabolism. Some babies showed a biphasic elimination pattern with elimination rates increasing after a few days. Although half-lives varied greatly, they corresponded well with renal clearance values and aminopyrine demethylase activities as measured by13CO2-exhalation from13C-labelled aminopyrine. Two newborns whose mothers had been treated with phenytoin in addition to primidone, showed half-lives, renal clearance values and aminopyrine demethylase activities well within the corresponding ranges for adults, thus demonstrating prenatal induction. Newborns whose mothers had been treated with valproate as comedication, did not exhibit elevated excretion rates as compared to newborns of mothers who were treated with primidone alone. Withdrawal symptoms developed in two newborns at times when primidone had been essentially excreted, and in spite of the presence of elevated phenobarbital and PEMA levels. All drugs studied were also present in mothers' milk. During breast feeding, drugs ingested with the milk contributed to the neonate's blood levels, particularly in the case of phenobarbital.
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  • 5
    ISSN: 1573-8221
    Keywords: induction ; phenobarbital ; albumin ; cytochrome P-450 ; immune response
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Definite interaction exists between the induction of microsomal enzymes and induction of the immune response to foreign substances. The loss by phenobarbital of its ability to induce the cytochrome P-450-hydroxylase system when bound covalently with albumin, coupled with the acquisition by phenobarbital of ability to induce a lymphocytic immune system reflects the ability of the two defensive systems of the body — hydroxylase and immune — to interact with foreign compounds of low and high molecular weight. The cytochrome P-450-hydroxylase system of the liver and other tissues is designed to protect the body against the action of low-molecular-weight hydrophobic compounds. The immune system is responsible for the protective effect against high-molecular-weight foreign substances.
    Type of Medium: Electronic Resource
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