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  • 1
    ISSN: 1432-1041
    Keywords: prostaglandins ; ductus arteriosus ; preterm infants ; HPLC-GC/MS
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-1041
    Keywords: benzodiazepine ; lormetazepam ; lormetazepam glucuronide ; transfer to milk ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-1041
    Keywords: Metamizole ; Furosemide ; prostaglandins ; drug interaction ; adverse effects ; pharmacokinetics ; pharmacodynamics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetic and pharmacodynamic interactions between metamizole (dipyrone) and furosemide were investigated in 9 of 12 healthy female subjects able to complete the study. They received oral metamizole 3×1 g for 3 days or placebo (cross-over) and on the last day of both study periods furosemide 20 mg IV. On the last two days a balanced sodium diet (120 mEq) and on Day 3 an oral water load (600 ml) were given. Metamizole significantly inhibited basal urine flow, whereas the fractional excretion of sodium and chloride and the 12 h-GFR remained unchanged. Metamizole significantly reduced furosemide clearance (175 vs 141 ml · min−1), furosemide-stimulated plasma renin activity (1.42 vs 0.79 ng AI · ml−1 · h−1) and the urinary excretion of prostacyclin metabolites and of prostaglandin F2α (by 70–81%). The renal clearance and terminal half-life of furosemide, peak renal chloride and volume excretion were unchanged. Thus, metamizole did not interact with the renal excretion and the diuretic effect of furosemide, although prostaglandin synthesis was significantly reduced.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-1076
    Keywords: Indomethacin ; Drug level monitoring ; Very low birth weight infants ; Ductus arteriosus
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract First results are described of individually tailored indomethacin dose rates employing on-line drug level monitoring for pharmacologically induced ductal constriction in very low birth weight infants with symptomatic patent ductus arteriosus (sPDA). In addition prolonged indomethacin therapy was introduced. From our data it appears that the effective threshold indomethacin level for the induction of ductus constriction has to be about 1000 ng/ml 10 h postdosing, while ductus closure can be maintained with a dose rate that exceeds a plasma level of 500 ng/ml for at least 1 week. These maintenance levels were also effective in completely suppressing the urinary metabolite excretion rates of PGI2 and PGE2, which are potential mediators of ductal relaxation. On-line indomethacin level monitoring appears to be practically essential for prolonged indomethacin therapy to overcome the marked variation of indomethacin disposition in preterm infants with sPDA.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-1076
    Keywords: Indomethacin ; Preterm infants ; Patent ductus arteriosus
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Fifteen preterm infants with patent ductus arteriosus and respiratory distress syndrome were given indomethacin (0.2 mg/kg) at 12 h intervals up to three times, either orally or intravenously, in an uncontrolled, non-randomized study. Serum indomethacin concentrations were determined in blood samples taken 12 h after dosing. There was considerable variability in the serum indomethacin concentrations, especially after oral administration, although the mean concentrations after each of the three doses were similar after both oral and intravenous administration. The frequency of closures and transient closures of the ductus arteriosus was also similar for both routes of administration. There was, however, no relation between concentration and effect in individual patients. The sustained exposure to indomethacin which appears to be necessary for ductal closure can sometimes be attained by oral administration.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1432-1076
    Keywords: Indomethacin ; Ductus arteriosus ; Intestinal perforation ; Necrotising enterocolitis ; Premature infant diseases
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Within 9 months we observed intestinal perforations in three very low birth weight (VLBW) infants undergoing indomethacin treatment for symptomatic patent ductus arteriosus (sPDA). The three patients exhibited striking similarities in their clinical courses and predisposing factors. Although clinical and histological criteria did not differentiate the perforations from necrotising enterocolitis (NEC), a well-known entity in premature infants, these events were remarkable to us since we had observed no other cases of NEC in recent years. From animal experiments and pathophysiological data, a role for indomethacin in gastrointestinal ischaemic damage must be considered. This communication is not meant to discredit indomethacin treatment. However, awareness of potential complications and careful monitoring during treatment is warranted.
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    European journal of pediatrics 147 (1988), S. 341-349 
    ISSN: 1432-1076
    Keywords: Eiosanoids ; Prostaglandins ; Modulation ; Mediation ; Early life
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Prostanoids are unsaturated cyclic fatty acids, are synthesized primarily from arachidonic acid, and, like the leukotrienes, belong to the growing family of eicosanoids. As tissue hormones, prostanoids act on specific receptors near their site of synthesis and degradation. Prostanoids operate as modulators and mediators in a large spectrum of physiological processes. They are involved in the regulation of maternal and fetal circulation, patency of the ductus arteriosus, plateletvessel wall interaction and kidney function. Besides their physiological function in protecting organ perfusion under stress conditions, they are also involved in diseases as described in the hyperprostaglandin E2-syndrome or — together with leukotrienes-in inflammatory processes. More specific pharmacological tools than the nonsteroidal antiinflammatory drugs, such as receptor antagonists, selective synthesis inhibitors, and eicosanoid analogues offer the prospect of enriching our arsenal of pharmacotherapeutic interventions in a variety of diseases. Before active intervention, however, more and specific biochemical analyses are required to identify the pathophysiological role of eicosanoid.
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  • 8
    ISSN: 1432-1041
    Keywords: prostanoid concentrations ; plasma ; gas chromatography/mass spectrometry ; PGE2 ; PGF2α ; 6-keto-PGF1α ; TxB2
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Plasma concentrations of PGE2, PGF2α, 6-keto-PGF1α and TxB2 were determined in 4 healthy volunteers by gas chromatography-negative ion chemical ionization mass spectrometry. TxB2 concentrations in all volunteers increased with time during blood collection, increases occurred more sporadically in the case of PGE2, PGF2α and 6-keto-PGF1α. Rapid changes in plasma prostanoid concentrations within a sampling series were unpredictable and were inexplicable. The measured plasma prostanoid concentrations apparently depended on the sampling conditions, which could not be adequately standardized and controlled. However, very short term changes in plasma prostanoid levels cannot be excluded.
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1432-1076
    Keywords: Indomethacin ; Drug level monitoring ; Infant, premature ; Ductus arteriosus, patent
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Indomethacin treatment for 1 week monitored by drug level determinations was evaluated in 32 preterm infants with symptomatic patent ductus arteriousus (sPDA). Inter- and intra-individual indomethacin dispositions varied considerably with the need for marked dosage adjustments to maintain the drug level within the proposed therapeutic range. The overall success rate of this prolonged treatment was 63%. There were no significant differences between the groups of responders (n=20), relapsers (n=5) and non-responders (n=7) with respect to postnatal age, sex, total indomethacin dose, and indomethacin serum concentrations. The responders, however, had significantly higher birth weights. Eighty-five percent of infants weighing more than 1000g (n=20) were treated successfully. Only four of these children experienced adverse reactions. The benefit-to-risk ratio was lowest in the group of infants weighing 1000 g or less (n=12) with a success rate of only 25% and, potentially, severe adverse reactions in ten infants. In conclusion, prolonged indomethacin treatment is an alternative to conventional short-term treatment and appears to be particularly efficacious and safe in infants weighing more than 1000 g. In infants weighing 1000 g or less and suffering from severe pulmonary diseases, this treatment cannot generally be recommended. The advantage of on-line drug level monitoring during indomethacin treatment deserves further investigation.
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  • 10
    ISSN: 1432-1076
    Keywords: Persistent ductus arteriosus ; Prematurity ; Indomethacin overdosage ; Side-effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We describe a preterm infant with severe idiopathic respiratory distress syndrome (iRDS, hyaline membrane disease) who needed artificial ventilation with high inspiratory pressure, high frequencies, 100% oxygen and developed a symptomatic patent ductus arteriosus (sPDA) in the course of the disease. The infant was given indomethacin to induce constriction of sPDA. Due to an error in drug dilution the patient received a 100-fold overdose of indomethacin. Compared to the normal study protocol side-effects such as renal failure were not observed probably due to sufficient fluid intake and good clinical condition prior to treatment and to the rapid and persistent ductal closure.
    Type of Medium: Electronic Resource
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