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  • 1
    Electronic Resource
    Electronic Resource
    Plasma and urinary excretion kinetics of oral baclofen in healthy subjects (1989)
    Springer
    European journal of clinical pharmacology 37 (1989), S. 181-184 
    Details
    ISSN: 1432-1041
    Keywords: baclofen ; renal function ; healthy subjects ; pharmacokinetics ; probenecid ; tubular secretion
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Baclofen, a centrally acting muscle relaxant, is used in the treatment of spasticity. Its pharmacokinetics has been derived from plasma and urine data in four healthy subjects, whose renal function was simultaneously measured. After oral administration of a single 40 mg dose, baclofen was mainly excreted unchanged by the kidney, 69 (14) %. The half-life, calculated from extended least squares modelling (ELSMOS) both of plasma and urine data was 6.80 (0.68) h, which is longer than reported in most studies based solely on plasma data. The renal excretion rate constant had the high mean value of 0.35 (0.24) h−1, and the apparent renal clearance of baclofen equalled the creatinine clearance. Passive tubular reabsorption is relatively unimportant, since no dependence was observed on variables urine flow or pH. Although active tubular secretion may contribute to its renal clearance, as shown by the effect of coadministration of probenecid, glomerular filtration appears to be the dominant transport mechanism.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00558228
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  • 2
    Electronic Resource
    Electronic Resource
    Kinetics of atrial natriuretic peptide in young and elderly subjects (1992)
    Springer
    European journal of clinical pharmacology 42 (1992), S. 449-452 
    Details
    ISSN: 1432-1041
    Keywords: Atrial natriuretic peptide ; kinetics ; ageing
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary To study the influence of age on the kinetics of atrial natriuretic peptide (ANP) in man, human (99–126) ANP 2.0 μg·min−1 was infused IV for 60 min in 8 healthy young (18 to 25 y) and 9 healthy elderly (71 to 84 y) subjects. Both baseline ANP values and the levels at the end of infusion were higher in the elderly subjects. The mean residence time of ANP in the two age groups was not significantly different, whereas total body clearance (CL) was markedly diminished in the elderly as compared to the young subjects (mean±SD 3.1±1.0 l·min−1 and 6.2±4.1 l·min−1, respectively). The apparent volume of distribution at steady state was lower in the elderly than in the young, but the difference was not significant (mean±SD 44±19 and 103±111, respectively. The decrease in CL largely explained the higher ANP levels found in the elderly subjects. The MRT and the plasma half-life of the terminal phase did not differ between the two groups. In the elderly but not in the young subjects the calculated endogenous creatinine clearance was closely correlated with the CL (r=0.90, P〈0.001), thereby emphasizing the importance of the kidney in the metabolic clearance of ANP in the elderly.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00280134
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  • 3
    Electronic Resource
    Electronic Resource
    The effect of the molecular structure of closely related N1-substituents of sulfonamides on the pathways of elimination in man (1983)
    Springer
    Pharmacy world & science 5 (1983), S. 49-56 
    Details
    ISSN: 1573-739X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Sulfadiazine, sulfamerazine, sulfadimidine and their corresponding N4-acetyl derivatives were administered to man. The percentages of acetylation and deacetylation, protein binding, half-lives of elimination and apparent and true renal clearance values were measured. Methyl substitution in the N1-pyrimidine ring favours acetylation by an additional N-acetyltransferase isoenzyme present in ‘fast’ acetylators only. Methyl substitution in the N1-pyrimidine ring favours renal clearance of the N4-acetylsulfonamide derivatives. The N1-substituent probably reinforces the binding of the N4-acetyl group to the active tubular transport mechanism. The renal clearance of these sulfonamides is not dependent on the structure of the N1-substituent.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01960075
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  • 4
    Electronic Resource
    Electronic Resource
    Effects of methoxy groups in the N1-substituent of sulfonamides on the pathways of elimination in man (1984)
    Springer
    Pharmacy world & science 6 (1984), S. 150-156 
    Details
    ISSN: 1573-739X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Sulfisomidine, sulfamethomidine, sulfadimethoxine and their corresponding N4-acetyl derivatives were administered to man. The percentages of acetylation and deacetylation and those of protein binding, the half-lives of elimination and the apparent and true renal clearance values were measured. No acetylation phenotype could be demonstrated in these compounds. Methoxy substitution in the N1-pyrimidine group of sulfisomidine affects predominantly the renal clearance value and mechanism of the parent compound but has no influence on the renal clearance of the N4-acetyl derivatives. The renal clearance value of sulfisomidine is 232±33 ml/min, of sulfamethomidine 21.60±16.4 ml/min and of sulfadimethoxine 10.87±10.44 ml/min. The renal clearance values of the corresponding N4-acetylsulfonamide derivatives are 314±91 ml/min, 342±63 ml/min and 202±65 ml/min respectively. Tubular reabsorption, caused by methoxy substitution in the N1-pyrimidine ring, lowers the rate of elimination and increases the half-life. The half-life of sulfisomidine is 8.5±0.5 h, of sulfamethomidine 27.8±5.3 h and of sulfadimethoxine 34.6±10.4 h.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01954042
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  • 5
    Electronic Resource
    Electronic Resource
    Comparison of linear and tapered intravenous infusion of methotrexate in oncochemotherapy. A theoretical approach (1985)
    Springer
    Pharmacy world & science 7 (1985), S. 158-162 
    Details
    ISSN: 1573-739X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract In oncochemotherapy with methotrexate (MTX) a peripheral concentration 〉0.45 mg/l and a plasma concentration 〈45 mg/l must be maintained for 20 h. The time periods required to reach and maintain steady-state concentrations after tapered and linear intravenous infusion were compared. Pharmacokinetic analyses according to a two-compartment model were used to calculate dosage regimens and concentration profiles by means of the Bayesian General Modelling Program (BM) and NONLIN. When the dosage regimen is based on a steady-state concentration in the peripheral compartment (which is the target compartment for MTX) tapered infusion reaches this concentration 40% faster and maintains it 12.5% longer, but no difference is found if the dosage regimen is based on a steady-state concentration in the central compartment. In theory the two-step 24-hour tapered infusion can be replaced by a bolus injection plus linear infusion in the ratio 1∶2 of the total dose. These dosage regimens are to be preferred over linear infusion.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02097253
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  • 6
    Electronic Resource
    Electronic Resource
    Clinical effects and pharmacokinetics of articainic acid in one volunteer after intravenous administration (1988)
    Springer
    Pharmacy world & science 10 (1988), S. 284-286 
    Details
    ISSN: 1573-739X
    Keywords: Articainic acid ; Drug evaluation ; Pharmacokinetics ; Pharmacology
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Articainic acid, a major metabolite of articaine, was administered to a volunteer. Since the renewed interest in the utilization of articaine in epidural anaesthesia, it has been important to assess the clinical effects of this metabolite. It was noted that articainic acid had no effect on EEG, ECG, blood pressure and heart rate. Pharmacokinetic parameters are given.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02219670
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  • 7
    Electronic Resource
    Electronic Resource
    Deterioration of kidney function by high doses of co-trimoxazole in man (1987)
    Springer
    Pharmacy world & science 9 (1987), S. 117-124 
    Details
    ISSN: 1573-739X
    Keywords: Clearance, renal ; Crystalluria ; Kidney diseases ; Metabolism ; Pharmacokinetics ; Pneumocystis carinii ; Sulfamethoxazole ; Trimethoprim
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract High doses of co-trimoxazole in a patient withPneumocystis carinii and impaired kidney function (creatinine clearance 10 ml/min) resulted in a declining renal clearance of the drug but did not affect the average creatinine clearance. The renal clearance of sulfamethoxazole and its metabolites 5-hydroxy-, N4-acetyl-, N4-acetyl-5-hydroxysulfamethoxazole decreased 80%, while the renal clearance of trimethoprim decreased 60%. The renal clearance of all compounds was evidently dependent on urine flow. The observed phenomena may be explained by the assumption that crystalluria occurred, obstructing kidney tubules. The crystalluria effect can be reversed by cessation of the drug or by lowering its dosage.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01960746
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