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  • Elimination  (2)
  • Key words Imidapril  (2)
  • 17-OHCS  (1)
  • 1
    ISSN: 1432-1041
    Keywords: Key words Imidapril ; Liver dysfunction; pharmacokinetics ; angiotensin-converting enzyme inhibitor
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Objective: The possible influence of impaired liver function on the pharmacokinetic disposition of imidapril, a novel prodrug type angiotensin-converting enzyme (ACE) inhibitor, and its active metabolite, imidaprilat, was investigated. Methods: Eight subjects with normal liver function and eight patients with liver dysfunction received an oral dose of 10 mg imidapril once daily for 7 days. Results: Plasma imidapril concentrations after single and, although less pronounced, after repeated dosing were higher in the liver disease patients, whereas imidaprilat concentrations were lower. This suggests that the conversion of imidapril into imidaprilat in the liver is delayed in patients with impaired liver function. However, the slower biotransformation did not result in statistically significant differences in Cmax and AUC for either imidapril or its active metabolite following repeated administration. Moreover, no relevant accumulation of either imidapril or imidaprilat occurred after repeated dosing. Conclusions: Imidapril is regarded as an ACE inhibitor of which the pharmacokinetic disposition is only slightly affected in patients with impaired liver function.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-1041
    Keywords: Key words Imidapril ; Chronic renal failure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Objective: An open study on the single dose and steady-state pharmacokinetics of imidapril, a novel prodrug-type angiotensin-converting enzyme (ACE) inhibitor, and its active metabolite imidaprilat was conducted in eight patients with moderate chronic renal failure [mean creatinine clearance (CLCR) 64 ml · min−1; range 42–77 ml · min−1], eight patients with severe chronic renal failure (mean CLCR, 18 ml · min−1; range 11–29 ml · min−1) and eight healthy volunteers with normal renal function. Subjects received an oral dose of 10 mg imidapril once per day for 7 days. Results: No statistical differences of either maximum concentration (Cmax) or the area under the curve (AUC) were found between patients with moderate renal failure and healthy subjects. However, Cmax and AUC for both imidapril and imidaprilat were significantly higher in patients with severe renal impairment than in healthy volunteers. There were no clinically relevant differences among the three subject groups with regard to total urinary excretion of both imidapril and imidaprilat. Conclusion: The smallest imidapril dose which is clinically effective should be used in patients with severe renal insufficiency.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 42 (1992), S. 641-644 
    ISSN: 1432-1041
    Keywords: Testosterone ; Enzyme Induction ; antipyrine ; phenobarbital ; rifampicin ; plasma testosterone ; urinary excretion ; FSH ; LH ; 6β-OH cortisol ; 17-OHCS
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effects of three different enzyme-inducing drugs (antipyrine 1200 mg, phenobarbital 100 mg, rifampicin 600 mg per day for 7 days) on plasma and urinary testosterone concentrations, plasma gonadotropin levels, antipyrine kinetics, and urinary 6β-hydroxycortisol excretion were studied in 18 healthy volunteers. Changes in plasma and urinary testosterone concentrations following exogenous testosterone undecanoate (TU) were also investigated. Although both antipyrine and rifampicin increased antipyrine clearance by about 60%, they produced contrary effects on testosterone: antipyrine lowered the total morning plasma testosterone and plasma testosterone AUC following TU, while rifampicin led to increases of about 20% and 78%, respectively. By contrast, phenobarbital did not significantly alter the endogenous and exogenous plasma testosterone concentrations, but it increased the urinary excretion of testosterone by more than 60%. The other two enzyme inducers did not alter this parameter. Gonadotropin levels remained unchanged. The results indicate that different enzyme-inducing agents exert divergent effects on endogenous and exogenous testosterone concentrations and suggest that the effect of enzyme induction on endogenous testosterone depends on the type of microsomal enzyme-inducing drug used rather than on the extent of the induction achieved.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Journal of molecular medicine 52 (1974), S. 1111-1116 
    ISSN: 1432-1440
    Keywords: Dextran 40 ; elimination ; renal function ; Dextran 40 ; Elimination ; Nierenfunktion
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung 36 Patienten mit unterschiedlicher Nierenfunktion (GFR zwischen 0,5–142 ml/min) erhielten 500 ml 10%iges Dextran 40 (Rheomacrodex®). Dabei ergab sich ein relatives Verteilungsvolumen von 10,2±2,2 1/100 kg. Die Eliminationshalbwertzeiten von Dextran 40 stehen mit der Nierenfunktion (51 Cr-EDTA-Clearance) in einem Zusammenhang, der sich rechnerisch am besten durch eine Potenzfunktion darstellen läßt. Patienten mit normaler Nierenfunktion (GFR über 90 ml/min) haben eine Eliminationshalbwertzeit von 573±138 min und eine 12 Std-Recovery im Urin von 48%. Ein Glomerulusfiltrat unter 10 ml/min führt dagegen zur Verlängerung der Halbwertzeit auf das Fünffache (Dextran 40-HWZ=2591±1022 min) und zum Rückgang der 12 Std-Recovery auf 4%. Im Clearancebereich zwischen 30 und 142 ml/min bleiben Eliminationshalbwertzeit und Urinausscheidung im wesentlichen konstant. Dextran 40 kann deshalb bei diesen Patienten nach den bekannten Regeln dosiert werden. Bei glomerulären Filtrationswerten unter 30 ml/min ist jedoch mit einer gestörten Elimination zu rechnen. Aus der veränderten Dextran 40-Ausscheidung im Urin und aus den Eliminationshalbwertzeiten ergeben sich Dosierungsrichtlinien, die diskutiert und tabellarisch aufgeführt werden.
    Notes: Summary 36 patients with different renal function (GFR=0.5−142 ml/min) received 500 ml of 10% dextran 40 (Rheomacrodex®). The relative distribution volume proved to be 10.2±2.21/100 kg. Dextran 40 half life time and renal function are correlated mathematically as a power function. In patients with normal renal function (GFR〉90 ml/min) we determined a dextran 40 half life time of 573±138 min and a 12 hour urinary recovery of 48%. In contrast to that a glomerular filtration rate below 10 ml/min prolongs the half-life five times to a value of 2591±1022 min and reduces the urinary elimination to 4% per 12 hours. In patients with a clearance between 30 and 142 ml/min no essential changes of half life time and urinary elimination can be observed. To those patients dextran 40 can be applied in the common dosage. Contrary to that a glomerular filtration rate below 30 ml/min leads to a prolonged elimination and consequently a different dosage has to be applied.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    Journal of molecular medicine 53 (1975), S. 523-527 
    ISSN: 1432-1440
    Keywords: Dextran 40 ; elimination ; dosage ; hemodialysis ; bleeding ; Dextran 40 ; Elimination ; Dosierung ; Hämodialyse ; Blutungen
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Bei 24 Hämodialysepatienten wurden nach einmaliger und wiederholter Gabe von Dextran 40 (Rheomacrodex®) die Dextranspiegel im Serum bestimmt und daraus die Eliminationshalbwertzeiten errechnet. Diese betrugen bei Heimdialysepatienten 2237±447 min, bei Zentrumsdialysepatienten 4283±810 min und waren damit gegenüber nierengesunden Patienten (HWZ=573±183 min) auf das Fünf- bzw. Zehnfache verlängert. Die Unterschiede zwischen Heimdialyse- und Zentrumsdialysepatienten erklären sich durch die bessere Nierenrestfunktion der ersteren. Während der Hämodialyse kam es zu keinem Abfall der Dextranspiegel i.S. Weiterhin zeigte sich, daß die exponentielle Elimination von Dextran 40 über einen Beobachtungszeitraum von 6,25 Tagen durch die intermittierende Hämodialyse nicht beeinflußt wurde. Da keine nennenswerte Ausscheidung von Dextran 40 durch die Hämodialyse erfolgt, braucht die intermittierende Hämodialyse bei der Dosierung nicht berücksichtigt zu werden. Die Dosierung von Dextran 40 hat sich jedoch streng nach der verlängerten Eliminationshalbwertzeit zu richten. Die Gabe von 2 × 50 g Dextran 40 pro Woche (2 × 500 ml 10%iges Dextran 40) kann schon nach der 4. Infusion zu Dextranspiegeln i.S. über 20 g/l und zu Blutungen führen. Um diese Komplikationen zu vermeiden, wird eine von der Nierenfunktion unabhängige Initialdosis vorgeschlagen mit einer anschließenden Erhaltungsdosis, die sich nach der Nierenfunktion richtet.
    Notes: Summary In 24 patients on regular hemodialysis the serum levels and the half-life of dextran 40 were determined after single or repeated infusion of dextran 40 (Rheomacrodex®). One group of hemodialysis trainees had a dextran 40 half-life of 2237±447 min. In contrast, a second group, consisting of hospital dialysis patients, had a dextran 40 half-life of 4283±810 min, whereas patients with normal renal function had a half-life of 573±183 min. The difference in dextran half-life between the two groups of hemodialysis patients may be explained by the better residual ronal function of our hemodialysis trainees. During hemodialysis no change in serum dextran levels could be observed. Intermittent hemodialysis, also, had no influence on the exponential elimination of dextran over a period of 6.25 days. Since hemodialysis by itself has no effect upon dextran elimination, the dosage of dextran 40 has to be adjusted to the prolonged elimination time only, disregarding dialysis. After the fourth infusion of 50 g dextran 40 (twice a week 500 ml of 10% dextran 40) serum dextran levels exceeding 20 g/l and cutaneous bleeding were observed. To avoid these complications an initial saturation dose is suggested, followed by a maintenance dose adjusted to the impaired renal function.
    Type of Medium: Electronic Resource
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