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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 24 (1983), S. 357-360 
    ISSN: 1432-1041
    Keywords: diazepam ; ranitidine ; pharmacokinetics ; hydroxycorticosteroids ; hepatic enzymes ; interaction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In 6 healthy volunteers the steady state pharmacokinetics of diazepam (5 mg p.o. once daily) was investigated in a randomized cross-over study with and without concomitant doses of ranitidine (150 mg bid). Following the last dose of diazepam on Day 10 of each part of the study, the plasma concentrations of diazepam were monitored for one dosing interval plus the subsequent 2 days. In addition, urinary excretion of 6-β-hydroxycortisol and 17-hydroxycorticosteroids were measured, their ratio being taken as an indicator of hepatic enzyme activity. Coadministration of ranitidine significantly reduced (p〈0.03) the trough and steady state concentrations (mean ± SD) of diazepam (114±36 Vs 104±30 ng/ml and 170±55 Vs 125±36 ng/ml, respectively). Plasma protein binding of diazepam (98.5±0.3%) was not affected by ranitidine. The half-life of elimination of diazepam (42.5±13.5 h) did not change significantly but its apparent oral clearance (assuming complete absorption) was significantly increased (p〈0.005) by ranitidine, from 22.6±9.2 to 30.0±9.1 ml/min. Urinary excretion of 6β-OH-cortisol (p=0.029) and 17-OH-corticosteroids (p=0.041) were significantly elevated by ranitidine, but their ratio did not change. In addition, in 4 additional subjects the disposition of diazepam following a single intravenous dose of 0.1 mg/kg was not significantly altered by ranitidine. Thus, the lowered steady state concentration of diazepam is most likely due to diminished absorption caused by the concurrent administration of ranitidine. However, it may be more important clinically that, unlike cimetidine, ranitidine did not impair the hepatic elimination of diazepam.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 21 (1981), S. 161-163 
    ISSN: 1432-1041
    Keywords: diazepam ; desmethyldiazepam ; product inhibition ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of a single intravenous dose of diazepam 0.1 mg/kg was studied in 6 healthy volunteers, in random order under controlled conditions and following pretreatment with its major metabolite, desmethyldiazepam (20 mg/day) for one week. In the two subjects with the highest plasma concentration of desmethyldiazepam (990 and 1100 ng/ml, respectively), total plasma clearance (Cl) of diazepam was reduced after desmethyldiazepam, by 31% and 54%, respectively. In three individuals there was a moderate decrease of 14% to 21%, and no effect was seen in one volunteer. Cl was significantly reduced (11.5±1.8 vs. 9.1±3.3 ml/min;p=0.015) and elimination half-life tended to be prolonged (38.5±10.4 vs. 65.8±67.1 h;p=0.15). It is concluded that high concentrations of desmethyldiazepam can influence the elimination of its parent drug diazepam by product inhibition.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 26 (1984), S. 223-226 
    ISSN: 1432-1041
    Keywords: diazepam ; metoprolol ; drug combination ; pharmacodynamics ; pharmacokinetics ; drug metabolism ; sedation ; interaction study
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In 6 normotensive, healthy male volunteers the pharmacodynamic responses (blood pressure, heart rate; sedation index, tracking test, reaction time) to metoprolol (100 mg bid orally), diazepam (0.1 mg/kg intravenously) and to their combination were studied. The pharmacokinetics of diazepam were also compared in a cross-over experiment, with and without pretreatment by the β-adrenoceptor antagonist to evaluate the possibility of a drug interaction. The pharmacodynamic and pharmacokinetic investigations indicated that metoprolol only slightly impaired the elimination of diazepam (18% decrease in total clearance, 25% increase in elimination half-life). The pharmacodynamics of metoprolol (17% decrease in heart rate, 17% decrease in diastolic RR) was not significantly altered by the bolus injection of diazepam. The extent of prolongation in choice reaction time (RT2) induced by diazepam was significantly (p=0.001) more pronounced following the co-administration of metoprolol. However, the results of RT1, the tracking test and the sedation index did not indicate any increased effect due to the β-blocking agent. It is concluded that concomitant treatment with metoprolol and diazepam causes only minor and clinically irrelevant changes in drug metabolism and drug response.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 0138-4988
    Keywords: Life Sciences ; Life Sciences (general)
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Process Engineering, Biotechnology, Nutrition Technology
    Notes: A fermentation process for manufacturing 1,4-piperazinium-(L,L)-dilactate from renewable raw materials and a method for processing this product into L,L-dilactide are described. Lactic acid fermentation with Lactobacillus paracasei was modified in such a way that pH control occurred by using an aqueous solution of piperazine as a correcting agent instead of sodium hydroxide solution. The production of a stoichiometrically composed piperazinium lactate was possible when the pH was 5.0. From 5.0 kg of glucose and 2.15 kg of piperazine, 6.65 kg of 1,4-piperazinium-(L,L)-dilactate were formed in the fermentation process. Separation from fermentation broth, purification and concentration of the product in aqueous solutions were carried out by means of ultrafiltration, nanofiltration and electrodialysis. Total product retention by the membranes used was about 33%. The crystalline salt was obtained by vacuum evaporation. Processing of the 1,4-piperazinium-(L,L)-dilactate into L,L-dilactide was performed in a special glass reactor. A product yield of 70% was achieved. The purified product was characterized by elementary analysis, as well as solubility behaviour, polarity and spectroscopic data. An overall process consisting of the stages fermentation, purification and concentration of piperazinium dilactate as well as cyclization of the latter to dilactide is described.
    Additional Material: 9 Ill.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Berlin : Wiley-Blackwell
    Acta Biotechnologica 7 (1987), S. 265-274 
    ISSN: 0138-4988
    Keywords: Life Sciences ; Life Sciences (general)
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Process Engineering, Biotechnology, Nutrition Technology
    Notes: A hybrid computer completes a scale up line to a computer coupled fermentation (CCF) system for data processing, monitoring and operator servicing, documentation and process control. Presented experiences using this arrangement were adapted and transferred to microcomputer systems.
    Additional Material: 2 Ill.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Berlin : Wiley-Blackwell
    Acta Biotechnologica 8 (1988), S. 147-150 
    ISSN: 0138-4988
    Keywords: Life Sciences ; Life Sciences (general)
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Process Engineering, Biotechnology, Nutrition Technology
    Notes: A significant difference between the maxima of the specific growth rate (μ) and the specific product formation (kp) may indicate a retarded correlation model of biomass (X) and product (P).Therefore phenomenological growth parameters which connect X and P or their derivations (Yp/x, kp) have to take into consideration this kind of lag-time in the same way.
    Additional Material: 3 Ill.
    Type of Medium: Electronic Resource
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