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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 45 (1993), S. 465-468 
    ISSN: 1432-1041
    Keywords: Benzoate ; Citrullinaemia ; hyperammonaemia ; ureagenesis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Although sodium benzoate therapy is beneficial in patients with inborn error of urea cycle, it has been suggested that an accumulation of benzoyl-CoA would inhibit ureagenesis. In this study, we examined several aspects of ureagenesis after the single oral dosing of sodium benzoate in six healthy subjects who participated in the study previously reported and in two patients with citrullinaemia. Urea nitrogen appearance (UNA) did not change after the doses of 40, 80 and 160 mg·kg−1 of sodium benzoate in the 6 healthy subjects. Sum of UNA and urinary hippurate nitrogen (UHN) increased with increasing the dose. In the 2 patients with late-onset citrullinaemia who benefit from a partially functional urea cycle, no apparent inhibitory effects on the UNA were observed after the administration of 80 mg/kg of sodium benzoate. The precursors of urea (ammonia, glutamate, glutamine and α-amino nitrogen) did not increase after the benzoate administration in the 6 normal subjects as well as in the 2 patients with citrullinaemia.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 41 (1991), S. 363-368 
    ISSN: 1432-1041
    Keywords: Benzoic acid ; hippuric acid ; pharmacokinetics ; hyperammonaemia ; ureagenesis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Plasma concentration-time data for benzoic and hippuric acids and urinary excretion-time data for hippuric acid were analyzed simultaneously after oral doses of 40, 80 or 160 mg/kg sodium benzoate administered at least one week apart to 6 healthy subjects. The mean AUCs of benzoic acid after the doses of 80 and 160 mg/kg of sodium benzoate were 3.7- and 12.0-times greater, respectively, than after 40 mg/kg. However, the mean AUC of hippuric acid was roughly proportional to the benzoate doses. The observed data were explained by a one-compartment model with first-order rate absorption and Michaelis-Menten elimination of benzoic acid, together with a one-compartment model with first-order elimination for hippuric acid. Although the maximum rate of biotransformation of benzoic acid to hippuric acid varied between 17.2 and 28.8 mg·kg−1·h−1 among the six individuals, the mean value (23.0 mg·kg−1·h−1) was fairly close to that provided by daily maximum dose (0.5 g·kg−1·day−1) recommended in the treatment of hyperammonaemia in patients with inborn errors of ureagenesis. The individual maximum rate of metabolism can be estimated from the urinary excretion rate of hippuric acid 1.5 to 3 h after the single oral dose of 80 to 160 mg·kg−1 sodium benzoate. The justification of this concept requires further studies in patients with inborn errors of urea synthesis.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 33 (1987), S. 85-88 
    ISSN: 1432-1041
    Keywords: theophylline ; aminophylline ; incremental concentration ; occlusion pressure ; maximum inspiratory pressure ; transdiaphragmatic pressure ; ventilatory function
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary To investigate the possible mechanisms by which theophylline affects the control of ventilation, neuromuscular drive and ventilatory function were examined in 7 healthy men receiving an incremental intravenous aminophylline dosing schedule to achieve plasma theophylline concentrations of 5, 10, and 15 µg/ml. As compared with the baseline (predose) values, the 3 incremental aminophylline doses significantly (p〈0.05 to 0.01) increased occlusion pressure (P0.1) and maximum inspiratory pressure static (MIPS) at functional residual capacity (FRC). This was not observed for ventilatory flow $$(\dot V)$$ , tidal volume (VT), inspiratory time to total breathing cycle time ratio (Ti/Ttot), VT/Ti, and effective impedance [P0.1/(VT/Ti)]. When maximum electrical activity of diaphragm (Edimax) and transdiaphragmatic pressure (Pdimax) were examined in 3 of the 7 subjects, Pdi/Edi tended to increase with increasing theophylline concentrations, while Edimax did not. Our results suggest that the increase in P0.1 during the increase in aminophylline dose is caused by an improvement in respiratory muscle contractility, rather than by a central effect or by an increase in neural drive.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 34 (1988), S. 55-59 
    ISSN: 1432-1041
    Keywords: doxapram ; ventilatory function ; occlusion pressure ; serum drug concentration ; concentration-effect relationship
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary To investigate the means by which doxapram affects the control of ventilation, ventilatory function and P0.1 have been related to serum doxapram concentration during a 45-min infusion of doxapram hydrochloride in 7 healthy, conscious subjects under normoxic conditions. Serum doxapram concentrations increased during the infusion: 1.88, 2.48, 3.42, and 3.97 µg/ml after 5, 10, 30 and 45 min, respectively. The majority of significant changes in the measurements from the baseline were observed at 30 and 45 min: $${{\dot V}}_{{E}}$$ , VT, P0.1, P0.1/end-tidal CO2 tension, VT/Ti and blood pressure were increased, and end-tidal CO2 tension was decreased. No significant changes in Pdimax, Ti/Ttot, $${{\dot V}}_{{E}}$$ /P0.1, and P0.1/(VT/Ti) were observed. A correlation was observed between the % increases in P0.1 and $${{\dot V}}_{{E}}$$ and doxapram concentration, and between $${{\dot V}}_{{E}}$$ and P0.1. The doxapram-induced increase in $${{\dot V}}_{{E}}$$ appears to be caused by increased neural drive. It is related to the serum drug concentration in the conscious subject.
    Type of Medium: Electronic Resource
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