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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 32 (1987), S. 289-295 
    ISSN: 1432-1041
    Keywords: theophylline ; pregnancy ; pharmacokinetics ; lactation ; methylxanthines ; metabolism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effects of pregnancy on the disposition of theophylline were assessed in 10 patients throughout pregnancy and post-partum. The clearance relative to total theophylline concentrations was only slightly affected during the first two trimesters (2.61±0.63 l/h and 2.85±1.05 l/h), while a statistically significant reduction was evident late in pregnancy (2.05±0.49 l/h). Post-partum clearance values (2.16±2.81 l/h) suggest an ongoing suppression relative to pre-pregnancy levels. A similar pattern was evident with clearance values based on free theophylline plasma concentrations (p=0.12). Absolute volume of distribution increased in concert with gestation, suggesting that theophylline partitions into the enlarged tissue spaces. In addition, theophylline binding to plasma proteins decreased, albeit insignificantly, during the second (fraction bound=29%) and third (32%) trimesters compared to post-partum values (41%). Increases in half-life during the third trimester (13.00±2.31 h vs 9.53±3.53 h post-partum) were highly significant. This change reflects the net effect of reduced clearance and increased distribution. Breast feeding had no effect on the disposition of theophylline, although the transfer of this compound into breast milk was confirmed.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 13 (1978), S. 303-308 
    ISSN: 1432-1041
    Keywords: Pharmacokinetics ; procainamide ; pharmacogenetics ; antiarrhythmic agent ; therapeutic serum concentrations ; constant rate infusion
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A pharmacokinetic approach was employed to design a dosing regimen for the i. v. use of procainamide (PA) which consisted of a loading infusion given over one hour followed by a maintenance infusion. Therapeutic serum concentrations of PA were achieved in less than 15 min, and toxic serum concentrations were avoided in 12 patients. A mean maximum serum concentration of PA of 5.78 mg/l was obtained with a loading infusion of 16.6 mg/min PA HCl. An average steady-state serum concentration of PA of 5.05 mg/l was obtained with a mean maintenance infusion of 222 mg/hour PA HCl. The total body clearance of PA in slow and fast acetylators averaged 31 and 43 l/h respectively. Use of PA in cardiac patients by i. v. infusion can be safe and effective therapy.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 19 (1981), S. 61-64 
    ISSN: 1432-1041
    Keywords: desipramine ; tricyclic antidepressant ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Disposition characteristics of desipramine and its metabolite, 2-hydroxy-desipramine, were determined in four healthy male volunteers following an oral 50 mg dose of desipramine. Nonlinear least-squares regression of concentration-time data indicated that parent drug disposition could be described by a one-compartment open pharmacokinetic model for two subjects and by a two-compartment model for two subjects. The early appearance of 2-hydroxydesipramine and its high peak concentrations indicates that desipramine probably undergoes pre-systemic elimination partly through formation of 2-hydroxy-desipramine. The substantial production of 2-hydroxy-desipramine, as reflected by the area under its concentration-time curve which was 51% to 94% of that for desipramine, indicates that accumulation will occur following multiple dosing. As 2-hydroxy-desipramine may possess antidepressant activity, future studies designed to assess the therapeutic effect of desipramine should account for the presence of its pharmacologically active metabolite.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 23 (1982), S. 429-433 
    ISSN: 1432-1041
    Keywords: methylprednisolone ; nephrotic syndrome ; high pulse dose ; pharmacokinetics adults ; children
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The disposition of a large pulse-dose of methylprednisolone was examined in paediatric and adult patients with the nephrotic syndrome. Plasma concentrations and urinary excretion rates were measured by high performance liquid chromatography. Most of the dose was metabolized, as indicated by urinary recovery of less than 10 percent of the dose. There was only slight age-dependence of the plasma clearance and volume of distribution of the steroid, although the T1/2 and mean transit time were shorter in younger patients. The pharmacokinetic parameters of the large doses (12–20 mg/kg) were similar to low dose (0.5–1 mg/kg) data from asthmatic patients. The limited variability of the pharmacokinetics of methylprednisolone suggests that tissue sensitivity may be a more important indicator of drug dosage needs in nephrotic syndrome.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 23 (1982), S. 129-134 
    ISSN: 1432-1041
    Keywords: theophylline ; ethinylestradiol ; oral contraceptives ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effect of chronic oral contraceptive (OC) usage on the disposition of theophylline was examined. Aminophylline solution (4 mg/kg) was given orally to 8 healthy female non-OC users and to 8 healthy women who were chronic (〉6 months) OC users. The OC user group had a significantly lower total plasma clearance of theophylline than women not using OC (35.1±5.6 vs. 53.1±14.5 ml/h/kg). The t1/2 was also significantly prolonged in the OC group (9.79±1.43 vs. 7.34±1.75 h) while the volume of distribution was similar between the 2 groups. The serum ethinylestradiol (EE) concentrations after oral OC administration were measured simultaneously. The apparent clearance of EE was about 30% lower in the OC users. A significant positive correlation was found between the apparent clearance of EE and the plasma clearance of theophylline. The effects of OC are predominantly due to chronic use with decreased elimination of both theophylline and EE.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 30 (1986), S. 323-329 
    ISSN: 1432-1041
    Keywords: methylprednisolone ; prednisolone ; pharmacokinetics ; healthy volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The disposition and plasma binding of methylprednisolone were examined in seven normal volunteers following the administration of 5, 20 and 40 mg of intravenous methylprednisolone sodium succinate. Methylprednisolone exhibits linear plasma protein binding averaging 77%. The mean plasma methylprednisolone clearance of 337 ml·h−1. kg−1 was independent of dose. The steroid appears to moderately distribute into tissue spaces with a mean volume of distribution of 1.41·kg−1. Methylprednisolone disposition parameters were compared with the non-transcortin bound parameters for prednisolone. The prednisolone plasma clearance based on the transcortin free-drug is similar to methylprednisolone total plasma clearance. However, the corrected volume of distribution of prednisolone is only one-half that of methylprednisolone. The disposition rate of these two steroids is thus similar, in spite of their metabolic control by different enzymatic pathways and major influence of saturable transcortin binding on prednisolone elimination.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 45 (1993), S. 581-583 
    ISSN: 1432-1041
    Keywords: Fluocortolone ; cortisol ; pharmacodynamics ; pharmacokinetics ; adrenal suppression
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effect of fluocortolone on cortisol suppression was characterized using a ‘direct suppression pharmacodynamic model’. The model incorporates the physiologic circadian secretion of cortisol under normal and treatment conditions, together with pharmacokinetic data from single fluocortolone doses of 20, 50, and 100 mg. A mean IC50 value (fluocortolone plasma concentration at which the circadian secretion of cortisol is inhibited by 50%) of 15.5 ng·ml−1 was found. This analysis shows how use of pharmacodynamic modeling can characterize dose-proportionality data to provide an in vivo measure of drug potency.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    Journal of pharmacokinetics and pharmacodynamics 6 (1978), S. 179-186 
    ISSN: 1573-8744
    Keywords: gentamicin ; nephrotoxicity ; prenephrotoxic identification
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract A computer method has been investigated to differentiate the prenephrotoxic patient from the nontoxic patient by routine monitoring of serum gentamicin concentrations duringtherapy, without the need to discontinue medication. The method deliberately assumes an incorreect pharmacokinetic model and uses a nonlinear regression program to analyze data collected during continuous dosing. In principle, it appears that the prenephrotoxic patients may be identified on the basis of a decreasing “apparent” elimination rate constant of gentamicin during continuous therapy.
    Type of Medium: Electronic Resource
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