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  • healthy volunteers  (17)
  • phosphorus
  • Springer  (24)
  • American Institute of Physics (AIP)
  • 1980-1984  (24)
Collection
Publisher
  • Springer  (24)
  • American Institute of Physics (AIP)
Years
Year
  • 1
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 27 (1984), S. 447-452 
    ISSN: 1432-1041
    Keywords: alaproclate ; antipyrine clearance ; serotonin reuptake inhibitor ; healthy volunteers ; antipyrine metabolism ; metabolite clearance ; alaproclate kinetics ; inhibition of drug metabolism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Alaproclate, a selective serotonin reuptake inhibitor, presently undergoing clinical trial for the treatment of major depressive disorders, has been shown to inhibit hexobarbital metabolism in mice. In the present study the influence of oral alaproclate on the total plasma clearance of antipyrine and on the formation of its metabolites was investigated in 10 healthy volunteers. The peak level of alaproclate was reached after about 1.5 h, and after a distribution phase, its plasma elimination half-life was between 3.0 and 3.5 h. Antipyrine tests were performed before treatment, during the first four doses and after the seventh dose of alaproclate 200 mg/day. During treatment, total plasma antipyrine clearance and the clearance for production of all antipyrine metabolites were reduced by 30%, indicating non-selective inhibition of oxidative drug-metabolizing enzyme activity in man by alaproclate. After the last dose of alaproclate, antipyrine plasma clearance and the clearance to its metabolites returned to control values. In order to allow more detailed evaluation of the results, the time course of the clearances for production of metabolites was investigated. This revealed that the extent of inhibition of metabolite formation by alaproclate was dependent on the plasma alaproclate level, indicating a rapidly reversible inhibition.
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 21 (1982), S. 433-441 
    ISSN: 1432-1041
    Keywords: antipyrine ; antipyrine metabolites ; drug metabolism ; route of administration ; healthy volunteers ; urinary excretion ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of antipyrine in plasma and saliva, and urinary excretion of its major metabolites, were studied following i.v. and oral administration of antipyrine 500 mg to 6 healthy volunteers. Data from both plasma and saliva showed that the oral bioavailability of antipyrine given as an aqueous solution was complete. The saliva/plasma concentration ratio was constant with time from about 3 h onwards, with a mean value of 0.87 after oral and 0.91 after i.v. administration. It is concluded that the pharmacokinetic parameters of antipyrine can be satisfactorily established on the basis of salivary data, although the volume of distribution and clearance values are then slightly too high. After i.v. administration, 3.8±1.9% of the dose was excreted in urine as unchanged antipyrine in 48h, 24.9±6.3% as 4-hydroxyantipyrine, 16.5±3.2% as norantipyrine, 13.0±2.2% as 3-hydroxymethyl-antipyrine and 5.8±1.0% as 3-carboxy-antipyrine. No significant differences were observed following oral administration. The half-lives calculated from the linear part of the urinary excretion rate curves of the metabolites were about the same for oral and i.v. administration, and were of the same order of magnitude as the elimination half-life of parent drug in plasma and saliva. It is important for determination of the ultimate metabolite ratio that urine is collected for at least 36h, because there is a delay in the excretion of 3-hydroxymethyl-antipyrine in urine.
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  • 3
    ISSN: 1573-5117
    Keywords: phosphorus ; nutrient cycling ; stratification ; epilimnion
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Phosphorus regeneration from lake sediments, and subsequent migration to trophogenic surface water, significantly contributes to the lake nutrient budgets and algal bloom conditions in some lake types. Decomposition of organic matter in deep water and sediments results in the accumulation of regenerated nutrients, alternate electron acceptors (reduced products of anaerobic respiration = COD), carbon dioxide, and depletion of dissolved oxygen (electron acceptor in aerobic respiration). Thermal stratification creates spatial segregation of trophogenic and tropholytic environments in the lake, resulting in gradients between sediments, hypolimnion, and the epilimnion. Exchange of oxygen, nutrients, and reduced alternate electron acceptors between the hypolimnion and epilimnion affects the productivity of a lake. Secchi depth, temperature, and dissolved oxygen profiles were determined twice each week from May 1980 to October 1980 at each of five lake stations. Nutrient concentration profiles, including total soluble and total phosphorus, ammonium-N, nitrate, soluble Kjeldahl, and total Kjeldahl nitrogen were determined twice each month. Epilimnetic algal samples were collected twice each week using Kemmerer and water column ‘straw’ amplers. Cell counts of total, green, bluegreen, and diatom algae groups were made. Three methods were used to describe hypolimnetic-epilimnetic exchange, including coefficients of eddy diffusion (based on lake heat budget), a graphical method of defining thermocline location, and relative thermal resistance to mixing (RTRM, based on density differences). All three methods yeilded comparable estimates of net seasonal transport. The graphical and RTRM methods described events occurring at shorter intervals (greater resolution). We find general agreement between the three methods of describing hypolimnetic-epilimnetic transport. The frequency of sampling resulted in increased resolution of thermal profiles (in time), allowing accurate estimation of short-term nutrient flux into epilimnetic waters. An algal bloom event occurred 5 to 12 days following erosion of the top of the metalimnion to below the aerobic-anaerobic interface. The lag time to peak algal concentration, following such events, decreased through the summer (June = 12 days, September = 5 days)
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  • 4
    ISSN: 1573-5117
    Keywords: phosphorus ; nutrient cycling ; stratification ; epilimnion
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Phosphorus regeneration from lake sediments, and subsequent migration to trophogenic surface water, significantly contributes to the lake nutrient budgets and algal bloom conditions in some lake types. Decomposition of organic matter in deep water and sediments results in the accumulation of regenerated nutrients, alternate electron acceptors (reduced products of anaerobic respiration = COD), carbon dioxide, and depletion of dissolved oxygen (electron acceptor in aerobic respiration). Thermal stratification creates spatial segregation of trophogenic and tropholytic environments in the lake, resulting in gradients between sediments, hypolimnion, and the epilimnion. Exchange of oxygen, nutrients, and reduced alternate electron acceptors between the hypolimnion and epilimnion affects the productivity of a lake. Secchi depth, temperature, and dissolved oxygen profiles were determined twice each week from May 1980 to October 1980 at each of five lake stations. Nutrient concentration profiles, including total soluble and total phosphorus, ammonium-N, nitrate, soluble Kjeldahl, and total Kjeldahl nitrogen were determined twice each month. Epilimnetic algal samples were collected twice each week using Kemmerer and water column ‘straw’ amplers. Cell counts of total, green, bluegreen, and diatom algae groups were made. Three methods were used to describe hypolimnetic-epilimnetic exchange, including coefficients of eddy diffusion (based on lake heat budget), a graphical method of defining thermocline location, and relative thermal resistance to mixing (RTRM, based on density differences). All three methods yeilded comparable estimates of net seasonal transport. The graphical and RTRM methods described events occurring at shorter intervals (greater resolution). We find general agreement between the three methods of describing hypolimnetic-epilimnetic transport. The frequency of sampling resulted in increased resolution of thermal profiles (in time), allowing accurate estimation of short-term nutrient flux into epilimnetic waters. An algal bloom event occurred 5 to 12 days following erosion of the top of the metalimnion to below the aerobic-anaerobic interface. The lag time to peak algal concentration, following such events, decreased through the summer (June = 12 days, September = 5 days)
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  • 5
    ISSN: 1573-5117
    Keywords: phosphorus ; nutrient cycling ; stratification ; epilimnion
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Phosphorus regeneration from lake sediments, and subsequent migration to trophogenic surface water, significantly contributes to the lake nutrient budgets and algal bloom conditions in some lake types. Decomposition of organic matter in deep water and sediments results in the accumulation of regenerated nutrients, alternate electron acceptors (reduced products of anaerobic respiration = COD), carbon dioxide, and depletion of dissolved oxygen (electron acceptor in aerobic respiration). Thermal stratification creates spatial segregation of trophogenic and tropholytic environments in the lake, resulting in gradients between sediments, hypolimnion, and the epilimnion. Exchange of oxygen, nutrients, and reduced alternate electron acceptors between the hypolimnion and epilimnion affects the productivity of a lake. Secchi depth, temperature, and dissolved oxygen profiles were determined twice each week from May 1980 to October 1980 at each of five lake stations. Nutrient concentration profiles, including total soluble and total phosphorus, ammonium-N, nitrate, soluble Kjeldahl, and total Kjeldahl nitrogen were determined twice each month. Epilimnetic algal samples were collected twice each week using Kemmerer and water column ‘straw’ amplers. Cell counts of total, green, bluegreen, and diatom algae groups were made. Three methods were used to describe hypolimnetic-epilimnetic exchange, including coefficients of eddy diffusion (based on lake heat budget), a graphical method of defining thermocline location, and relative thermal resistance to mixing (RTRM, based on density differences). All three methods yeilded comparable estimates of net seasonal transport. The graphical and RTRM methods described events occurring at shorter intervals (greater resolution). We find general agreement between the three methods of describing hypolimnetic-epilimnetic transport. The frequency of sampling resulted in increased resolution of thermal profiles (in time), allowing accurate estimation of short-term nutrient flux into epilimnetic waters. An algal bloom event occurred 5 to 12 days following erosion of the top of the metalimnion to below the aerobic-anaerobic interface. The lag time to peak algal concentration, following such events, decreased through the summer (June = 12 days, September = 5 days)
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 19 (1981), S. 53-55 
    ISSN: 1432-1041
    Keywords: digoxin ; bioavailability ; dose-dependency ; urinary excretion ; healthy volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Nine healthy volunteers received single 0.25, 0.5, 1.0, 1.5, and 2.0 mg doses of oral digoxin tablets in random sequence on five occasions separated by at least 4 weeks. Urinary excretion of immunoassayable digoxin was determined from 8 consecutive 24 h urine samples collected after each dose. Mean values of cumulative urinary excretion of digoxin at the 5 doses were: 40.9, 35.6, 36.4, 34.1, and 33.5% of the dose (F=0.64; d. f.=4.32; N. S.). Mean values of urinary excretion half-life were: 2.48, 2.03, 2.20, 2.07, and 1.87 days (F=2.87; d. f.=4.32;p=0.05). Thus, the bioavailability of orally administered digoxin tablets in healthy volunteers is dose-independent over an 8-fold range of doses.
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 26 (1984), S. 635-637 
    ISSN: 1432-1041
    Keywords: theophylline ; inhalation ; saliva-serum distribution ; healthy volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Six healthy volunteers received an iv infusion of 317 mg lysine theophylline (equivalent to 197 mg anhydrous theophylline) in order to calculate theophylline clearance by standard methods. They subsequently received a 20 minute inhalation of nebulised lysine theophylline. Serum and salivary theophylline concentrations were measured and all saliva was collected for the first hour. From these concentrations estimates were made of the distribution of theophylline into the blood and saliva with 40% to 94% identified in the blood. Very high salivary concentrations were reached during the inhalation phase with saliva: serum concentration ratios of between 60 and 1600.
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  • 8
    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.
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  • 9
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 27 (1984), S. 471-475 
    ISSN: 1432-1041
    Keywords: acyclovir ; A515U ; 6-deoxyacyclovir ; pharmacokinetics ; prodrug ; antiviral chemotherapy ; healthy volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A515U (6-deoxyacyclovir) is an analogue of acyclovir devoid of antiviral activity in vitro but which is well absorbed and undergoes conversion to acyclovir after oral administration to rats. The tolerance and pharmacokinetics of various doses of A515U have been studied in 8 healthy volunteers. Single oral doses of 25, 50, 100, 200 and 400 mg A515U and 400 mg acyclovir for comparison were administered to the volunteers at weekly intervals. Concentrations of the parent drug and acyclovir were determined in plasma and urine. The prodrug was well tolerated and did not cause adverse reactions or changes in haematological or biochemical variables. It was well absorbed and conversion to acyclovir was rapid and extensive at all doses. Plasma concentrations of acyclovir achieved with 50 mg A515U orally were comparable to and less variable than those produced by 400 mg acyclovir. A515U was rapidly cleared with a short plasma elimination half life of approximately 0.5 h. The attainment of high plasma concentrations of acyclovir by oral administration of a prodrug may represent an important advance in antiviral chemotherapy.
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  • 10
    ISSN: 1432-1041
    Keywords: benzodiazepine antagonist ; visual function ; intrinsic effect ; Ro 15-1788 ; healthy volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Ro 15-1788 is a specific benzodiazepine antagonist, which has also been shown to have some agonist properties. Since benzodiazepine receptors are involved in the physiological mechanisms of vision, a possible intrinsic effect of Ro 15-1788 was sought in 6 healthy volunteers by study of psychophysical flicker thresholds, including critical fusion frequency and low frequency modulation threshold, and pattern reversal visual evoked response, using double blind cross-over methodology. In each session 2 tablets of Ro 15-1788 30 mg were administered. Using a two factorial univariate analysis of variancé, no change was detected in any of the parameters studied.
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