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  • metoclopramide  (2)
  • acetylsalicylic acid  (1)
  • autoinduction  (1)
  • 1
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 20 (1981), S. 465-471 
    ISSN: 1432-1041
    Keywords: metoclopramide ; pharmacokinetics ; bioavailability ; first-pass effect
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The time courses of plasma metoclopramide concentrations were followed in six subjects after oral and intravenous single dose administration. Plasma concentration-time data following i.v. administration in each subject were found to fit a two compartment model with a mean terminal half-life of 4.55 h±0.80 h and a mean distribution half-time of 0.35 h±0.09 h. Volumes of distribution were high (3.43±1.181 · kg−1), and clearances (0.53±0.191 · kg−1h−1) approached liver plasma flow. This suggests that metoclopramide occurs at higher concentrations in tissues than in plasma, and that its clearance is probably limited by liver blood flow rather than liver metabolic capacity. The post-absorption decline in metoclopramide plasma levels after oral administration was also biexponential in each subject. The terminal half-life was 5.17 h±0.98 h. Mean volume of distribution and mean clearance were similar to intravenous values (after adjustment for bioavailability). Oral absorption was rapid with peak plasma concentrations being reached at a mean time of 0.93 h. A mean bioavailability of 0.77 was calculated for the six subjects, and it was postulated that this incomplete availability is due to a first-pass effect. The inter-individual variation in the degree of ‘first-pass’ was considerable (0.47–1.14).
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 24 (1983), S. 777-785 
    ISSN: 1432-1041
    Keywords: aspirin ; migraine ; salicylic acid ; metoclopramide ; drug absorption ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of aspirin (ASA) in acute migraine attacks, and the influence of metoclopramide on ASA disposition, were studied in 32 attacks in 30 patients. An intergroup comparison was made between normal volunteers, and the migraineurs, who were assigned at random to one of three treatment groups: a) oral ASA only (900 mg); b) 10 mg oral metoclopramide + oral ASA 900 mg; c) 10 mg i. m. metoclopramide + oral ASA 900 mg. Plasma ASA and SA levels were measured serially over 2 h, and the resultant data evaluated pharmacokinetically. Metoclopramide plasma levels were also determined over 2 h, and the results compared with a second group of normal volunteers. The rates of oral ASA absorption and elimination were unaffected by migraine. Mean absorption rate constants of 14.15±9.48 h−1 (normals), 7.91±3.42 h−1 (ASA only), 6.74±3.26 h−1 (ASA + oral metoclopramide) and 8.12±2.82 h−1 (ASA + i. m. metoclopramide) were calculated. Mean elimination rate constants ranged from 2.56 h−1 to 3.37 h−1, and did not differ significantly between controls and migrainous patients. Values for absorption lag time, however, were higher in migraine patients treated with ASA alone than in any other group. The amount of ASA absorbed unhydrolysed was also lower in this group. SA levels appeared unaffected either by the migraine attack, or by metoclopramide administration, over the period of study. Metoclopramide plasma levels were significantly lower during migraine attacks, and the amount of drug absorbed up to 2 h from dosing was also reduced, as compared with non-migrainous subjects. It was concluded that acute migraine caused a delay in orally administered ASA reaching its absorption sites, probably as a result of gastric stasis, and may have decreased the amount of ASA absorbed. The prior administration of metoclopramide, either orally or intramuscularly, reduced the absorption lag time, and thus promoted the early absorption of ASA, probably by restoring alimentary tract motility.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-1041
    Keywords: acetylsalicylic acid ; salicylic acid ; effervescent tablets ; enteric coated tablets ; liquid chromatography ; platelet aggregation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Single doses of effervescent tablets (1200 mg) and enteric coated (EC) tablets (1300 mg and 650 mg) of acetylsalicylic acid (aspirin, ASA) were given to healthy volunteers in random order. Plasma ASA and salicylic acid (SA) levels were measured and concurrent in vitro measurements of the volunteers' platelet aggregation were carried out. The effervescent preparation resulted in peak ASA concentrations of 17–40 mg/l, achieved 20 to 30 min after a 1200 mg dose, whereas peak ASA levels of 0.01–0.37 mg/l were observed 4–6 h after a 650 mg dose of the EC preparation. With all the aggregating agents that were added to the test system maximum inhibition of platelet aggregation (about 50% of pre dose levels) was seen 1.0 h after the effervescent ASA dose, and persisted to at least 24 h, but with the EC preparation not until 24 h, at which time the degree of inhibition was also about 50% of pre-dose levels. A 1.0 g dose of sodium salicylate had no effect on in vitro platelet function. It was concluded that mean plasma levels of ASA of less than 0.25 mg/l are sufficient to depress aggregation by approximately 50%. A low dose of ASA taken daily either as effervescent ASA or EC ASA, significantly inhibits platelet aggregation and so may reduce the risk of ischaemic episodes in susceptible patients.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 47 (1994), S. 355-360 
    ISSN: 1432-1041
    Keywords: Carbamazepine ; metabolism ; autoinduction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Six healthy young adult male volunteers were given two 600 mg (2540 μ moles) oral doses of carbamazepine (CBZ) 5 days apart. Serial concentrations of CBZ and its 10,11-epoxy (CBZ-epoxide) and 10,11-dihydro-10,11-trans-dihydroxy (CBZ-diol) metabolites in plasma, and daily excretions of these substances and the 2-hydroxy (2-OH-CBZ), 3-hydroxy (3-OH-CBZ) and 9-hydroxymethyl-10-carbamoylacridan (acridan) metabolites in urine were followed for 5 days after each dose. Pharmacokinetic analysis showed that autoinduction of CBZ metabolism was present within 6–10 days of the initial drug dose. The mean oral clearance of CBZ increased from 1.48 to 1.74 l·h− (difference 0.26 l·h−, 95% confidence interval 0.11 to 0.41 l·h−) and the mean percentage urinary recovery of the amount of CBZ eliminated increased from 41.8% to 44.6% (difference 2.8%, 95% confidence interval 0.5 to 5%) between the two studies 5 days apart. The data for daily clearance to metabolite and the time-courses of the plasma CBZ-epoxide to CBZ and CBZ-diol to CBZ concentration ratios suggested that autoinduction had begun by the second day after CBZ intake, and involved not only the epoxide-diol pathway but, to a lesser extent, the oxidations to phenolic derivatives.
    Type of Medium: Electronic Resource
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