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  • 1980-1984  (7)
  • pharmacokinetics  (7)
  • urinary excretion  (3)
  • 1
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 23 (1982), S. 327-330 
    ISSN: 1432-1041
    Keywords: bendroflumethiazide ; cantharides plasters ; blister fluid ; plasma levels ; pharmacokinetics ; compartmental analysis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of bendroflumethiazide (BFT) was investigated following the oral administration of 10 mg to 3 healthy volunteers. Each subject participated twice in the study. BFT was determined in plasma and cantharides blister fluid from 1/2 to 30 h post administration. Blister fluid was obtained from blisters 10–22 h old. Plasma levels were fitted to a tri-exponential equation and the concentration of the drug in the peripheral compartment was calculated from the microscopic rate constants. In 5 of 6 cases investigated, cantharides blister fluid levels paralleled the concentration of the drug in the peripheral compartment. The mean blister fluid levels exceeded the calculated concentration in Compartment 2 1.46 fold. In one case, the blister fluid level paralleled the plasma level. This subject clearly differed from the others as more than 10 h were required for blister formation in her. The results suggest that following the administration of BFT, cantharides blister fluid behaves as part of the peripheral compartment. The possible value of studying blister fluid levels in pharmacokinetic investigations is discussed.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 24 (1983), S. 661-665 
    ISSN: 1432-1041
    Keywords: hydrochlorothiazide ; pharmacokinetics ; renal failure ; dosage adjustment ; excretory mechanism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of hydrochlorothiazide (HCT) was investigated in 23 subjects with normal renal function or widely varying degrees of renal failure. The half-life of elimination increased from 6.4 h in subjects with normal renal function to 11.5 h in patients with mild renal impairment (endogenous creatinine clearance between 30 and 90 ml/min), and to 20.7 h in patients with an endogenous creatinine clearance below 30 ml/min. The cumulative urinary excretion and the renal HCT clearance were correspondingly reduced in patients with impaired kidney function. In normal subjects HCT was mainly excreted by tubular secretion, but as renal HCT clearance in patients with renal impairment did not differ significantly from endogenous creatinine clearance, it was concluded that the secretory mechanism is most markedly impaired. In patients with an endogenous creatinine clearance of 30 to 90 ml/min, the dosage of HCT should be reduced to 1/2 and in patients with a endogenous creatinine clearance below 30 ml/min to 1/4 of the normal daily dose to avoid dose dependant side-effects.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 25 (1983), S. 237-241 
    ISSN: 1432-1041
    Keywords: triamterene ; bioavailability ; pharmacokinetics ; metabolism ; hydroxy triamterene sulphate ; urinary excretion ; i.v. administration ; first-pass-effect
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary With a new formulation, which made intravenous infusion of triamterene (TA) possible, plasma levels and urinary excretion rates of TA and its main metabolite (OH-TA-ester) were measured in a randomized, cross-over trial in 6 healthy volunteers given triamterene 10 mg i.v. and 50 mg p.o. TA and OH-TA-ester were determined by densitometric measurement of native fluorescence after thin layer chromatography. Distribution volumes of the central compartment of TA and OH-TA-ester were 1.49 l/kg and 0.11 l/kg, respectively. Terminal half-lives were 255 min for TA and 188 min for OH-TA-ester after i.v. administration. For TA total plasma clearance was 4.5 l/min and renal plasma clearance 0.22 l/kg. The formation of OH-TA-ester was very rapid and the concentration of the metabolite exceeded that of TA at all times. After i.v. administration the urinary recovery of TA and OH-TA-ester was 4.4% and 50.9%, respectively. The bioavailability of TA was 52%, corresponding to absorption of 83%. TA is partly eliminated by a first-pass-effect. The main metabolite of TA is OH-TA-ester, which is pharmacologically active.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 19 (1981), S. 65-71 
    ISSN: 1432-1041
    Keywords: atenolol ; haemodialysis ; renal failure ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of atenolol were determined following acute intravenous and chronic oral administration to 20 subjects with a glomerular filtration rate (GFR) between 5 and 113 ml/min. Plasma levels in a further 5 patients on haemodialysis were measured after intravenous treatment. The mean half life of elimination increased from 5.9 h in patients with normal renal function to 42.1 h in preuraemic patients (GFR 〈10 ml/min) following a single i. v. dose. The half life of elimination following chronic oral administration was not significantly different. Mean peak plasma concentrations increased from 540 ng/ml in patients with normal renal function to 1493 ng/ml in preuraemic patients following chronic oral treatment with 100 mg/day. The mean half life of elimination during a single haemodialysis treatment was 4.3 h. In patients with a GFR 〉30 ml/min the normal daily dose of atenolol should be employed, in patients with a GFR between 10 and 30 ml/min the dose should be reduced by half, and in patients with a GFR 〈10 ml/min a reduction by three quarters of the normal dose is recommended.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 21 (1982), S. 315-323 
    ISSN: 1432-1041
    Keywords: bendroflumethiazide ; propranolol ; hydralazine ; pharmacokinetics ; thin-layer chromatography ; fluorimetry ; fixed combination product
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Bendroflumethiazide (Bft) was administered to 6 healthy subjects at 3 different dose levels (2.5, 5 and 10 mg) in a cross-over design, either as capsules (2.5 mg) or as tablets (5 mg). Its pharmacokinetics were evaluated then and following administration of a fixed combination of Bft with propranolol and hydralazine to a further 7 volunteers. Plasma and urinary concentrations of Bft were determined by a new fluorimetric — thin-layer chromotography procedure. Peak plasma levels occurred after 2–3 h and averaged 15, 27 and 45 µg/l in the three dose groups. Areas under the plasma concentration — time curves (AUC0→12), which were 75, 147 and 250 µg l−1 h respectively, and cumulative urinary recovery (20%) were independent of the dose administered and the type of formulation. Thus Bft kinetics proved to be linear within the dose range evaluated. The plasma clearance was calculated to be 505 ml/min, renal clearance 108 ml/min and nonrenal clearance 396 ml/min. Bioavailability of Bft was not altered following administration of the fixed combination. The amount of propranolol found in the circulation did not change, whereas that of hydralazine (determined as apparent hydralazine) increased by 59% when the fixed combination was administered.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 24 (1983), S. 453-456 
    ISSN: 1432-1041
    Keywords: triameteren ; renal failure ; hydroxytriamterene sulphate ; pharmacokinetics ; plasma protein binding ; urinary excretion ; renal tubular secretion
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The kinetics of triamterene and its active phase II metabolite were studied in 32 patients with various degrees of impaired renal function; the creatinine clearances ranged from 135 to 10 ml/min. The area under the plasma concentration-time curves (AUC) for triamterene were not influenced by kidney function, but the AUCs for the effective metabolite OH-TA-ester were significantly elevated in renal failure, indicating accumulation of the metabolite. Urinary recovery of triamterene and its metabolite over a 48 h collection period was significantly reduced in renal failure. This is considered to be due to delayed urinary excretion, corresponding to reduced renal clearance. The renal clearance of the native drug exceeded that of the metabolite, because of their different protein binding, 55% for triamterene and 91% for the metabolite. The latter is eliminated almost exclusively via tubular secretion and extrarenal elimination is less important. Administration of this antikaliuretic is therefore considered hazardous in patients with impaired kidney function.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 26 (1984), S. 125-127 
    ISSN: 1432-1041
    Keywords: nadolol ; pharmacokinetics ; plasma levels ; urinary excretion ; bioavailability ; circadian rhythm
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In 7 healthy subjects (3 males and 4 females), the kinetics of nadolol was investigated after oral doses of 60 and 120 mg. The t1/2 was 14.0±1.8 h. The peak plasma level was doubled on doubling the dose (from 69±15 to 132±27 ng/ml, respectively) and the urinary excretion (13.5%) rose similarly. The half-life of elimination was longer at night than in the day, probably because of the slower nocturnal flow of urine.
    Type of Medium: Electronic Resource
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