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  • pharmacokinetics  (5)
  • occlusion pressure  (2)
  • Benzoic acid  (1)
  • 1
    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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  • 2
    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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  • 3
    ISSN: 1432-1041
    Keywords: carteolol ; pharmacokinetics ; beta-adrenoreceptor blocking drug ; absolute bioavailability ; plasma levels ; urinary excretion ; renal handling
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics and absolute bioavailability of a new nonselective β-adrenoreceptor blocking agent, carteolol, were investigated after administration of single intravenous and oral doses to eight normal volunteers. Plasma and urine drug concentrations were measured by an HPLC method. The pharmacokinetic parameters after intravenous dosing were obtained by a two-compartment analysis: elimination or β-phase t1/2 4.7±0.3 h; Vc, 0.74±0.101/kg; Vd, 4.05±0.48 l/kg; Cl, 10.13±0.94 ml/min/kg; ClR, 6.56±0.58 ml/min/kg; and ClNR, 3.57±0.40 ml/min/kg. The absolute bioavailability obtained from plasma data was 83.7±8.0%, which was consistent with that derived from analysis of urine of 82.7±4.2%. The amounts excreted unchanged in urine up to 48 h after the intravenous and oral doses were 65.0±1.5% and 53.8±3.2% of the administered doses, respectively. The t1/2 for removal of the drug derived from plasma and urine findings after intravenous and oral dosing were similar, which indicates that the main route of elimination of carteolol is via the kidneys. As the ClR of carteolol exceeded the Cl of creatinine there may be renal tubular secretion of the drug.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-1041
    Keywords: ketoprofen ; pharmacokinetics ; relative bioavailability ; single doses ; repeated doses ; prediction of kinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of ketoprofen was studied in the same healthy subjects after single oral, intramuscular and rectal doses, and after repeated oral administration. No significant difference in the mean t1/2 (1.13–1.27 h) was observed after the different modes of administration. The mean [AUC] 0 ∞ after rectal administration of a suppository showed the minimum significant difference (p〈0.05) from that after oral administration of the capsule. The apparent volume of distribution (Vd/F) was approximately 10–15% of body weight. The renal contribution (mean, 0.10–0.15 ml/min/kg) to the plasma clearance of free ketoprofen was assumed to be, at most, 8.3–12.9%. The projected cumulative excretion of total (free plus conjugated) ketoprofen via urine exceeded 63–75% of the dose, of which approximately 90% was ketoprofen glucuronide. A mean of 71–96% and 73–93% of the oral capsule was estimated to be systemically available after administration of the intramuscular preparation and rectal suppository, respectively. In four of seven subjects, CPK concentration was elevated after the intramuscular injection. The mean steady-state concentration of ketoprofen in plasma ranged from 0.43 to 5.62 µg/ml after the final dose of a 50 mg q.i.d. regimen. The disposition data and plasma levels observed at steady-state were in agreement with those predicted from the single oral dose study. The accumulation ratio was 1.08±0.08. The results suggest that the rectal suppository can be recommended as an extravascular mode of administration of this drug.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-1041
    Keywords: theophylline ; smoking habit ; absolute bioavailability ; pharmacokinetics ; sustained release preparation ; plain tablet preparation ; antipyrine pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The bioavailability and pharmacokinetics of theophylline from a plain uncoated and 2 newly designed, sustained-release tablet formulations, as compared to intravenous aminophylline, were studied in 12 healthy adult male volunteers. The subjects were divided into two groups (n=6) with respect to smoking habit and on 4 separate occasions each received, on a randomized cross-over basis, a single dose of 400 mg equivalent of theophylline from every dosage form. The intravenous aminophylline study showed that habitual smoking had a significant (p〈0.05) effect on plasma theophylline clearance (0.051±0.006 vs 0.035±0.004 l/kg/h). Smoking significantly reduced the raw AUC from the 4 dosage forms (p〈0.05), but did not change the characteristics of absorption of each formulation. There was a non-significant trend towards reduced absolute bioavailability of theophylline from sustained-release formulations in smokers (percentage mean difference — 16% for one formulation and 13% for another). The trend was not observed for the plain uncoated tablet, which was rapidly absorbed (p〈0.01 to 0.05 in Ka, tmax and Cmax compared to sustained-release tablets). Similarity of the in vitro dissolution profiles of the two sustained-release formulations did not imply similarity of the in vivo absorption characteristics. Plasma clearances of theophylline and antipyrine were significantly correlated (p〈0.05,r=0.693,n=10). Thus, smoking enhanced the elimination of theophylline regardless of the dosage form administered. However, the extent to which habitual smoking may affect the hepatic first-pass effect on theophylline from sustained-release formulations requires further study. The results also suggest that theophylline and antipyrine may share a similar or common and presumably polycyclic hydrocarbon-inducible form(s) of microsomal drugmetabolizing enzyme.
    Type of Medium: Electronic Resource
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  • 6
    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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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 44 (1993), S. 493-495 
    ISSN: 1432-1041
    Keywords: Timolol ; β-adrenoceptor antagonist ; transdermal ; percutaneous absorption ; skin ; pharmacokinetics ; bioavailability ; adverse effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetic profiles of transdermal timolol 6 and 24 mg (as 5 and 20% w/v patches) was studied in four healthy young volunteers. To assess its bioavailability, the pharmacokinetics of an IV infusion of timolol maleate 5 mg was also determined in the same subjects. When the 20% (w/v) timolol patch was applied, the mean bioavailability was 74.4%. Plasma timolol concentrations were below the detection limit when a 5% patch was applied to the same skin area in all four subjects, except for one in whom the bioavailability was 23.6%. Weak erythema developed at the application site in all of the volunteers after application of the 20% (w/v) patch. However, erythema did not develop in any volunteer when the 5% patch was applied. The β-blocking effect was determined by exercise testing. Similar plasma levels generated similar changes in exercise-induced heart rate after the transdermal and intravenous administration of timolol.
    Type of Medium: Electronic Resource
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