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  • 1
    Electronic Resource
    Electronic Resource
    Serum concentration of piroxicam and inhibition of platelet aggregation in patients with rheumatoid arthritis and M. Bechterew (1994)
    Springer
    Inflammation research 43 (1994), S. 48-52 
    Details
    ISSN: 1420-908X
    Keywords: Platelet aggregation ; Piroxicam ; ADP ; Epinephrine ; Collagen
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract An open trial was conducted in 22 in-patients with classic or definite rheumatoid arthritis (RA) and 17 in-patients with M. Bechterew with the aim to investigate the effect of increasing concentrations of piroxicamin vivo on the platelet aggregation in such patients. In all patients therapy with piroxicam (10 mg/d) was started after with-drawing other non-steroidal antiinflammatory drugs. In 36 cases the daily dose of piroxicam was increased to 20 mg/d and in five cases to 30 mg/d based on clinical judgment. The platelet aggregation in platelet-rich plasma (PRP) caused by epinephrine, ADP (both 5 μM) and collagen (2 μg/ml) was measured at the beginning of the trial and before each dose increase. The results of the trial suggest that a significant positive correlation exists between increasing serum concentrations of piroxicam and the degree of inhibition of platelet aggregation, caused by all three platelet aggregation agonists. This action of piroxicam was most pronounced when epinephrine was used as platelet agonist.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02005764
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  • 2
    Electronic Resource
    Electronic Resource
    Influence of the cytochrome P4502D6*4 allele on the pharmacokinetics of controlled-release metoprolol (1998)
    Springer
    European journal of clinical pharmacology 54 (1998), S. 469-474 
    Details
    ISSN: 1432-1041
    Keywords: Key words CYP2D6 ; Genetic polymorphism ; Metoprolol ; Pharmacokinetics ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Aim: The aim of the present paper was to compare the pharmacokinetics of metoprolol in homozygous Caucasian volunteers for the wild-type CYP2D6 allele (CYP2D6*1/CYP2D6*1) and heterozygous (CYP2D6*1/CYP2D6*4) Caucasians. Methods: Thirty-six unrelated healthy male Caucasians were screened for two of the most frequently occurring mutant alleles (CYP2D6*3 and CYP2D6*4) using polymerase chain reaction (PCR). Twenty-four volunteers with a genotype suggesting a rapid hydroxylator phenotype were enrolled in a bioequivalence trial and each received in a randomized, cross-over fashion one of the three formulations compared. Each formulation contained 200 mg metoprolol tartrate/(tablet). In each of the three periods of the trial, one of the formulations was administered under fasting conditions in the morning on 4 consecutive days. Blood for quantification of metoprolol was drawn immediately before the last dose and in selected time intervals thereafter. A sensitive and specific high-performance liquid chromatography (HPLC) method with fluorescence detection was applied for the quantification of metoprolol. Pharmacokinetic parameters were determined for each subject and statistically compared in two groups of 16 homozygous (CYP2D6*1/CYP2D6*1) and six heterozygous (CYP2D6*1/CYP2D6*4) volunteers. Results: Significant differences between homozygous and heterozygous individuals were observed for all pharmacokinetic parameters. The AUC in the course of one those interval of 24 h (AUCτ), minium steady-state concentration (Cmin ss) and average steady-state concentration (Cav ss) values for heterozygous individuals were more than twice those of individuals. Significantly higher values for Css max , t1/2, half-value duration (HVD) and mean residence time (MRT) were also observed in heterozygous volunteers. The higher concentrations of metoprolol in heterozygous individuals also had pharmacodynamic consequences, namely, greater heart rate and blood pressure reduction.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002280050495
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  • 3
    Electronic Resource
    Electronic Resource
    On the pharmacokinetics of pengitoxin and its cardioactive derivative 16-acetyl-gitoxin (1983)
    Springer
    European journal of clinical pharmacology 25 (1983), S. 369-373 
    Details
    ISSN: 1432-1041
    Keywords: pengitoxin ; pharmacokinetics ; 16-acetylgitoxin ; absorption ; urinary excretion ; healthy subjects ; cardiac glycoside
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of pengitoxin has been studied in 28 healthy subjects after intravenous and oral administration. The mean plasma concentration 24 h after 0.5 mg i.v. was 5.2 ng · ml−1. Following an open two-compartment model a mean elimination half-life of 60.5 h (24.9 to 103.5 h) and a mean volume of distribution (Vdarea) of 66.91 (31.8 to 109.61) were calculated. Absorption calculated by comparison of the AUC0-∞-values amounted to 99%. Within 4 days, 16.7% (11.7 to 21.1%) or 27.8% (18.4 to 33.7%) (0.5 mg i.v. or 1.2 mg p.o.) was excreted in urine. After pengitoxin 0.5 mg i.v. total body clearance and renal clearance were 13.3 ml · min−1 (7.0 to 18.6 ml · min−1) and 3.0 ml · min−1 (1.9 to 3.9 ml · min−1) respectively. The elimination half-life of pengitoxin is longer than that of digoxin and distinctly shorter than that of digitoxin, whilst its distribution volume and clearance are closer to those of digitoxin than of digoxin.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01037950
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  • 4
    Electronic Resource
    Electronic Resource
    Effect of diprafenone on the pharmacokinetics of digoxin (1996)
    Springer
    European journal of clinical pharmacology 50 (1996), S. 97-100 
    Details
    ISSN: 1432-1041
    Keywords: Key words Diprafenone ; Digoxin ; Drug interaction; antiarrhythmics ; human pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract This study was conducted to investigate the effect of diprafenone on the steady-state pharmacokinetics of digoxin. Twelve healthy men, all rapid hydroxylators of debrisoquine, received digoxin (0.5 mg per day over 7 days with a loading dose of 2 × 1 mg) or digoxin and diprafenone (3 × 100 mg per day) in three different phases, without a wash-out period (phase 1, digoxin alone; phase 2, digoxin + diprafenone; phase 3, digoxin alone). Blood and urine samples were collected for pharmacokinetic analyses. Diprafenone caused a statistically significant increase in digoxin trough concentrations [1.4 (SD 0.2) vs 1.6 (0.3) ng ⋅ml−1], AUC0–24 values [41 (7) vs 48 (9) ng⋅h⋅ml−1 and Css-max [3.9 (0.6) vs 5.5 (0.9) ng⋅ml−1]. In all volunteers the parameters tended to return to the original values after administration of diprafenone was discontinued [1.4 (0.3) ng⋅ml−1, 39 (11) ng⋅h⋅ml−1, and 3.9 (1.1) ng⋅ml−1 for trough concentration, AUC0–24 and Cmax respectively]. The mean relative magnitude of the increase in AUC0–24 and trough concentration values corresponded to the mean relative decrease in the renal clearance of digoxin (in both cases approximately 20%). This suggests that the increase in AUC and Css was caused by reduced renal clearance of digoxin.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002280050075
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  • 5
    Electronic Resource
    Electronic Resource
    Influence of food on the bioavailability and some pharmacokinetic parameters of diprafenone – a novel antiarrhythmic agent (1996)
    Springer
    European journal of clinical pharmacology 50 (1996), S. 315-319 
    Details
    ISSN: 1432-1041
    Keywords: Key words Diprafenone; antiarrhythmics ; bioavailability ; human ; foods ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Objective: The present study was done to investigate the effect of food on the bioavailability of diprafenone. Methods: The most important pharmacokinetic parameters (Cmax, t1/2, AUC) and the relative oral availability of a solid oral preparation of racemic diprafenone were investigated when administered to fasting subjects and 10 min after a standard meal, in an open, randomised, crossover trial. Single oral doses of 100 mg were given on two different occasions, at least 1 week apart. The serum concentrations of diprafenone and its hydroxy-metabolite were determined up to 24 hours after administration by a sensitive, specific HPLC method. Fifteen healthy, male volunteers were enrolled in the trial. Their mean height, weight and age were 183 cm, 80 kg and 22 years, respectively. Fourteen volunteers were found to be rapid hydroxylators and one was a slow hydroxylator of debrisoquine. Only data from the rapid hydroxylators were used in the statistical analysis. Results: Food increased the oral bioavailability of diprafenone by approximately 50%. This effect was similar in rapid and in slow hydroxylators. The only slow hydroxylator in this trial had an AUC0–last ratio (with food/fasting) of 1.54. These findings suggest that diprafenone should be administered in a constant temporal relationship to food.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002280050115
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  • 6
    Electronic Resource
    Electronic Resource
    Differences in the bioavailability of dihydrotachysterol preparations (1994)
    Springer
    European journal of clinical pharmacology 47 (1994), S. 81-84 
    Details
    ISSN: 1432-1041
    Keywords: Dihydrotachysterol ; bioavailability ; pharmacokinetics ; human ; HPLC
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract The bioavailability of four preparations containing dihydrotachysterol (DHT2) was tested in two separate trials with administration of single, oral doses of 1 mg per individual. The relative bioavailability of corresponding preparations (capsules vs capsules and oral solution vs oral solution) was tested in a randomised, crossover pattern within the same group of volunteers. Two different groups of 24 healthy volunteers took part in each trial. Solution and capsule bioavailability was also compared inter-individually. A new sensitive HPLC-method (quantification limit 0.5 ng · ml-1) was used for the measurement of DHT2 concentration in serum. Three of the preparations tested had a similar bioavailability (mean AUC values of 195.5–223 ng · h · ml-1); the bioavailability of the fourth preparation (A.T.10 oral solution) was considerably lower (mean AUC value 111.5 ng · h · ml-1). The present dosage recommendations of all four preparations are identical. A new dosage recommendation is thus required for the oral solution with low bioavailability (A.T.10).
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00193484
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  • 7
    Electronic Resource
    Electronic Resource
    Absolute bioavailability of oral immediate and slow release fluphenazine in healthy volunteers (1996)
    Springer
    European journal of clinical pharmacology 51 (1996), S. 183-187 
    Details
    ISSN: 1432-1041
    Keywords: Key words Fluphenazine; bioavailability ; human ; slow release formulation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Objective: The present study was conducted with the aim of investigating the absolute bioavailability of fluphenazine in healthy volunteers after administration of immediate and slow release oral formulations. Methods: The oral dose was 12 mg fluphenazine hydrochloride. The intravenous bolus dose was 2.5 mg. Fourteen healthy volunteers of both sexes were enrolled in this randomised, crossover trial. Twelve volunteers completed the trial according to protocol. Results: The concentration maxima after administration of the slow release formulation were approximately half those measured after the immediate release formulation and were recorded later by a factor of 2 (immediate release: Cmax = 2.3 ng⋅ml−1, tmax = 2.8 h; slow release: Cmax = 1.2 ng⋅ml−1, tmax = 4.6 h). The concentrations measured 10 min after intravenous bolus administration of 2.5 mg fluphenazine hydrochloride were approximately 100 times higher (261 ng⋅ml−1). The geometric means for the absolute bioavailability of fluphenazine were 2.7% for the immediate release formulation and 3.4% for the slow release formulation. The absolute bioavailability of fluphenazine is thus much lower than previously generally accepted.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002280050182
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