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  • Chlormethiazole  (2)
  • canrenone  (2)
  • elderly  (2)
  • 1
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of chlormethiazole in humans (1975)
    Springer
    European journal of clinical pharmacology 8 (1975), S. 353-357 
    Details
    ISSN: 1432-1041
    Keywords: Chlormethiazole ; pharmacokinetics ; man ; plasma levels ; gas-liquid chromatography
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of chlormethiazole have been studied in six healthy volunteers following an intravenous infusion of the drug. The log. plasma concentration-time curve of chlormethiazole after cessation of the infusion was found to be curvilinear and was fitted therefore, by a bi-exponential equation computed by non-linear least squares regression analysis. Half-lives for the inital α-phase (0.54±0.05 h) and the terminal β-phase (4.05 ±0.60 h) were calculated together with other pharmacokinetic parameters of the two compartment open model. An explanation for the discrepancy between the presently reported plasma half-lives and those appearing in the literature has been presented. The pharmacokinetic treatment of the plasma concentration-time data obtained following intravenous infusion also enabled the prediction that the maximal systemic availability of an orally administered dose of chlormethiazole would be of the order of 15%.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00562662
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  • 2
    Electronic Resource
    Electronic Resource
    The pharmacokinetics of amiloride-hydrochlorothiazide combination in the young and elderly (1989)
    Springer
    European journal of clinical pharmacology 37 (1989), S. 167-171 
    Details
    ISSN: 1432-1041
    Keywords: amiloride ; hydrochlorothiazide ; pharmacokinetics ; steady-state ; elderly ; fixed combination
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of amiloride and hydrochlorothiazide were studied in 12 healthy young volunteers following a single dose of a fixed combination of amiloride and hydrochlorothiazide and in 11 elderly hypertensive patients at steady-state. Following modelling of the single dose data, simulated steady-state plasma concentrations for the 2 drugs were generated to examine the effect of age and/or hypertension on pharmacokinetics. The apparent systemic plasma clearance for both amiloride and hydrochlorothiazide was significantly reduced in the elderly when compared to the young (from 753 to 325 ml·min−1, amiloride; and from 418 to 157 ml·min−1, hydrochlorothiazide). The plasma concentrations at steady state for both drugs were greatly increased in the elderly patients (Amiloride: from 7 to 25 ng·ml−1, Css,max; from 2 to 8 ng·ml−1, Css,min; and from 4 to 14 ng·ml−1, Cav; Hydrochlorothiazide: from 184 to 651 ng·ml−1, Css,max; from 31 to 121 ng·ml−1, Css,min; and from 89 to 273 ng·ml−1, Cav). The decreased clearance of the diuretics in the elderly was believed due to deterioration of renal function, and there was a significant correlation between the plasma clearance of hydrochlorothiazide and creatinine clearance in both age groups (r=0.62, young;r=0.72, elderly). As a result of the pharmacokinetic findings caution may be indicated in the clinical dosage of the diuretics particularly when in fixed dose combination.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00558226
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    Paper (German National Licenses)
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  • 3
    Electronic Resource
    Electronic Resource
    Plasma level of chlormethiazole and two metabolites after oral administration to young and aged human subjects (1977)
    Springer
    European journal of clinical pharmacology 12 (1977), S. 137-145 
    Details
    ISSN: 1432-1041
    Keywords: Chlormethiazole ; pharmacokinetics ; metabolites ; oral administration ; young and elderly human subjects ; quantitative gas chromatographymass spectrometry ; whole blood distribution
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The plasma concentration of chlormethiazole and two of its metabolites has been measured in three young and three aged human subjects following administration of a single oral dose of chlormethiazole. A sensitive analytical method based on gas chromatography-mass spectrometry using the selective ion monitoring mode of operation was developed to permit quantitation of the plasma levels. The time course of the plasma concentration of chlormethiazole and metabolites showed wide inter-subject variation, particularly between the young and elderly subjects. Absorption of chlormethiazole was rapid in the subjects of both groups as assessed by the time taken to reach the peak plasma concentration. The mean peak plasma level of chlormethiazole was more than five times greater in the elderly (2.90±1.56 µg/ml) than in the young (0.55±0.58 µg/ml) subjects. The plasma level of chlormethiazole was consistently higher in the aged subjects and this was reflected by the larger area under the plasma curve in aged (7.62±5.37 µg.h/ml) than in young (0.94±0.66 µg.h/ml) individuals. Decreased pre-systemic elimination by the liver has been suggested as an important factor contributing to the higher plasma level in the elderly. Estimates of absolute systemic availability, calculated by reference to previous intravenous studies, were greater for the elderly subjects. The distribution of chlormethiazole in whole blood from six young and six elderly human subjects was investigated in vitro. The unbound fraction of chlormethiazole in plasma increased significantly from 0.308±0.035 in young subjects to 0.403±0.067 in the elderly. Distribution of the drug in whole blood was different for the two age groups; the fraction of drug distributed to plasma water was significantly greater and the fraction in blood cells was significantly less in the aged.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00645135
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    Paper (German National Licenses)
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  • 4
    Electronic Resource
    Electronic Resource
    Comparison of plasma levels of canrenone and metabolites after base hydrolysis in young and elderly subjects following single and multiple doses of spironolactone (1984)
    Springer
    European journal of clinical pharmacology 27 (1984), S. 435-439 
    Details
    ISSN: 1432-1041
    Keywords: canrenone ; spironolactone ; elderly patients ; single and multiple doses ; plasma protein binding
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Plasma levels of canrenone and ‘total metabolites’ after base hydrolysis were compared in young and elderly subjects following single and multiple doses of spironolactone. After the initial dose on Day 1, plasma levels of canrenone and ‘total metabolites’ were higher in the young than in the elderly group, and significant differences were found between the two age groups in the AUC for both canrenone and ‘total metabolites’. However, these differences between the two age groups diminished after multiple dosing on Day 8, and the steady state predose plasma levels of canrenone and ‘total metabolites’ were significantly higher in the elderly subjects. The accumulation ratios of canrenone and ‘total metabolites’ were significantly higher in the elderly than in the young subjects. Both canrenone and canrenoic acid were extensively bound to plasma protein, but no differences were found between the two age groups in protein binding. Observed differences in plasma levels after single and multiple dosing between young and old subjects may be consequences of many factors such as 1.) a proportionate shift in metabolism with age; 2.) impaired oral absorption of the parent compound; and/or 3.) altered volume of distribution of the drug.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00549591
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  • 5
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of canrenone and metabolites after base hydrolysis following single and multiple dose oral administration of spironolactone (1984)
    Springer
    European journal of clinical pharmacology 27 (1984), S. 441-446 
    Details
    ISSN: 1432-1041
    Keywords: spironolactone ; canrenone ; metabolites ; pharmacokinetics ; single/multiple oral doses ; healthy volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of canrenone and ‘total metabolites’ after base hydrolysis was studied in eight young volunteers following single and multiple dose oral administration of spironolactone. The plasma levels of canrenone and ‘total metabolites’ were fitted to a two-compartment open model with a first-order absorption process. From our eight normal subjects studied, the harmonic mean of the distributive half-life (t1/2α) of canrenone was found to be 1.66 h, and the harmonic mean of the terminal elimination half-life (t1/2β) to be 22.6 h. Harmonic means of the distributive and elimination half-lives of ‘total metabolites’ after base hydrolysis were 2.48 h and 28.8 h respectively. The accumulation ratio of canrenone was 2.53, whereas that of ‘total metabolites’ was 1.89. Despite the fact that spironolactone has been shown to induce hepatic metabolism of other drugs, no evidence of autoinduction was noted in the present study, as plasma levels of canrenone and ‘total metabolites’ were found to obey a linear two-compartment model with reproducible absorption and disposition after single and multiple doses.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00549592
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    Paper (German National Licenses)
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  • 6
    Electronic Resource
    Electronic Resource
    Systemic availability of orally administered L-dopa in the elderly Parkinsonian patient (1980)
    Springer
    European journal of clinical pharmacology 17 (1980), S. 215-221 
    Details
    ISSN: 1432-1041
    Keywords: L-dopa ; elderly ; pharmacokinetics ; bioavailability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Previous studies have suggested that the absorption of L-dopa in the elderly Parkinsonian patient might be unusually efficient. In the present investigation, the systemic availability of L-dopa was examined in 5 elderly Parkinsonian patients (mean age=77 years) and 6 young, healthy volunteers (mean age=26 years) following a single oral 300 mg dose of L-dopa. Quantitation of plasma levels of intact L-dopa was effected by ion-exchange column chromatography and spectrofluorimetry. The L-dopa plasma concentration-time profiles obtained confirmed the considerable intersubject variability in the absorption of L-dopa previously reported in the literature. Maximum plasma concentrations of L-dopa generally occurred within 60 min of administration of the dose. The existence of more than one plasma peak of L-dopa concentration was displayed in 45% of the subjects studied. This characteristic was not confined exclusively to either subject group. There was a significantly larger (P〈0.02) area under the plasma L-dopa concentration-time curve (AUC o ∞ ) in the elderly Parkinsonian patients (mean=234.69 µg · min/ml; SD=84.70) compared to the young, healthy volunteers (mean=82.33 µg · min/ml; SD=31.00). A significant (P〈0.01) correlation existed between AUC o ∞ and age (r=0.7970; n=11) among the subjects studied. The apparent elimination phase plasma half-life of L-dopa in the elderly Parkinsonian patients (mean=66.0 min; SD=11.1) was not significantly different to that observed in the young, healthy volunteers (mean=74.0 min; SD=18.1). These results suggest that there may be an age-related alteration to the disposition of orally administered L-dopa in the elderly Parkinsonian patient.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00561903
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    Paper (German National Licenses)
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