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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 23 (1982), S. 267-270 
    ISSN: 1432-1041
    Keywords: terodiline ; human volunteers ; pharmacokinetics ; serum clearance ; bioavailability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of terodiline HCl was studied in nine healthy volunteers given 12.5 mg i.v. and p.o. or 20 mg i.v. and 25 mg p.o. on two different occasions. The serum concentrations were measured by gas chromatography — mass spectrometry, using deuterated terodiline HCl as the internal standard. After i.v. administration the kinetics could be described by a two-compartment model with a mean distribution half life of 0.3 h and a mean elimination half life of 63 h. The serum clearance and apparent volume of distribution varied about 4-fold with mean values of 4.8 l/h and 417 l, respectively. After oral administration, the mean half life of absorption was 0.7 h and that of elimination 65 h. The absolute bioavailability varied between 64% and 105% with a mean of 92%. The long serum half life of terodiline should permit its once daily administration.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 29 (1985), S. 477-481 
    ISSN: 1432-1041
    Keywords: budesonide ; glucocorticoid ; nasal administration ; pharmacokinetics ; bioavailability ; systemic effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Budesonide, a topically potent glucocorticoid, was administered to 4 healthy volunteers by i.v. infusion and by nasal instillation of 100 µg tritium-labelled drug. Plasma was analyzed by liquid chromatography plus scintillation counting of collected fractions. After i.v. administration the plasma clearance was 0.92 l/min and the apparent volume of distribution was 2.8 l/kg. After nasal administration, the time to reach the peak plasma level was approximately 30 min, and the systemic availability was 102%. Budesonide had marginal effects on plasma cortisol and white blood cell counts either after i.v. or nasal administration. Thus, nasally instilled budesonide in solution is rapidly and completely absorbed from the nasal mucosa. The systemic effects after this clinically recommended nasal dose were negligible.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-1041
    Keywords: enprofylline ; healthy subjects ; absorption ; pharmacokinetics ; oral- ; duodenal- ; colonic administration
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Enprofylline, a new potent bronchodilator xanthine drug, was given orally as an aqueous solution to 6 healthy subjects in single doses of 2, 4 and 6 mg/kg. The two lower doses produced plasma concentrations in the range 1–4 mg/l, i.e. in the assumed “therapeutic interval” according to previous animal studies. A high 24 h urine recovery of unchanged drug, with mean values for the three dose levels ranging from 85 to 91% of the given dose, indicated good absorption and little metabolism. The dose-corrected area under the plasma concentration-time curve rose with dose as the latter was increased from 2 to 6 mg/kg. This indicates that the elimination of enprofylline is capacity-limited at high doses. Double peaks in the plasma concentration-time curves at the higher dose levels suggested intermittent and delayed gastric emptying as a possible explanation. This hypothesis was confirmed by studies in 6 other healthy subjects, who received the drug solution by three different routes; by mouth, via a catheter in the duodenum, and rectally via a catheter in the colon. The corresponding time to peak values (mean±SEM) were 32.5±8.7, 13.3±2.5, and 157±23 min.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-1041
    Keywords: milrinone ; renal impairment ; hypertension ; pharmacokinetics ; healthy subjects ; antihypertensive effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Milrinone, a new, nonglycosidic inotropic agent with peripheral vasodilating properties, was given as a single oral 5 mg dose to 7 healthy subjects, 7 patients with moderate renal impairment (CRI I, creatinine clearance 30–63 ml/min) and 7 patients with severe renal impairment (CRI II, creatinine clearance 9–29 ml/min). All except one of the patients with renal impairment had hypertension. The mean urinary recovery of milrinone was 82% in healthy subjects, the renal clearance was 288 ml/min and the plasma half-life (t1/2) was 0.94 h. In CRI the mean plasma t1/2 was prolonged (CRI I 1.78 h, CRI II 3.24 h). There was a significant linear relationship between creatinine clearance and the elimination rate constant, and between creatinine clearance and the renal clearance of milrinone. During the study day there was a tendency to a decrease in supine BP from 1 to 6–8 h after dosing, with the maximal decrease at 2–3 h (healthy subjects 118/71→107/56, CRI 159/95→136/79 mmHg). The same degree of change was seen in standing BP. A slight rise in standing HR was seen from 2–6 h after dosing. Changes in BP and HR are difficult to evaluate since the study was not placebo-controlled. The plasma elimination rate of milrinone was decreased in CRI and dose adjustment may be necessary. Placebo-controlled studies of milrinone in hypertensive patients would be required to validate its possible antihypertensive effect.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 30 (1986), S. 421-425 
    ISSN: 1432-1041
    Keywords: nimodipine ; subarachnoid haemorrhage ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Patients with a ruptured supratentorial aneurysm undergoing early surgery after the subarachnoid haemorrhage were treated postoperatively with nimodipine to prevent delayed ischaemic dysfunction. It was given first as a continuous intravenous infusion 2 mg/h (mean dose 0.5 µg/kg/min) for at least 7 days, and then orally (45 mg × 6) for at least a further 7 days. During the i.v. infusion, the mean plasma concentration was 26.6±1.8 ng/ml. The plasma clearance ranged from 0.57 to 1.77 l/kg/h and was negatively correlated with the age of the patient. Immediately prior to successive oral doses, the mean plasma concentration was 13.2 ng/ml (range〈3–38.8 ng/ml). The peak level was usually found after 1 h; it ranged from 7.0–96.0 ng/ml. Mean bioavailability was 15.9%. The nitropyridine metabolite was found in measurable concentrations only after oral treatment with nimodipine. In some cases, the concentration of metabolite exceeded that of the parent compound. The three patients investigated who developed delayed ischaemic dysfunction had plasma concentrations well within the range in patients who did not, so it seems unlikely that the therapeutic failure could be attributed to individual deviations in the pharmacokinetics of the drug.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 10 (1976), S. 25-29 
    ISSN: 1432-1041
    Keywords: Digoxin ; exchange transfusion ; pharmacokinetics ; neonates ; 86Rb assay
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary By means of an86Rb-uptake inhibition assay, changes in the plasma concentration of digoxin and the amount of the glycoside removed during exchange transfusion have been studied in two newborns. For comparison, the exchange procedure was simulated by a computer on the basis of a two-compartment open model and available pharmacokinetic constants. A rapid decrease in plasma digoxin concentration during exchange transfusion was found when the glycoside was administered intravenously or intramuscularly within 60 min before the procedure. The amount of digoxin removed by the exchange was less than 6 per cent of the given dose. Computer simulation of the procedure also showed removal of only a minor amount of digoxin. It is concluded that the decrease in plasma concentration and the removal of only a small amount of glycoside by the exchange transfusion can be attributed mainly to extensive tissue distribution of digoxin. The results imply that replacement of digoxin after an exchange transfusion seems unnecessary.
    Type of Medium: Electronic Resource
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