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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 46 (1994), S. 473-475 
    ISSN: 1432-1041
    Keywords: Phenobarbitone ; phenobarbitone-N-glucoside ; urine ; metabolism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract The elimination of phenobarbitone (PB) was studied in 14 chronically treated epileptic patients under steady state conditions. PB, [S]-PB-N-glucoside ([S]-PB-N-G) and p-hydroxy-PB (p-OH-PB) were assayed in urine by a HPLC method. Some 57 % of the daily dose was recovered in urine, 14 % as [S]-PB-N-G, 16 % as p-OH-PB (conjugated plus non-conjugated) and 27 % as unaltered PB. Thus PB-N-G formation contributed significantly to the elimination of PB during long-term administration of the drug, and there was reason to suspect that some of the PB-N-G formed may have already been degraded to untraced products before excretion from the body.
    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
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 24 (1983), S. 727-732 
    ISSN: 1432-1041
    Keywords: propranolol ; foetus ; placenta ; metabolism ; pregnancy ; plasma levels ; plasma protein binding ; delivery
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Propranolol (P) and all of its major known metabolites were found in maternal plasma, cord plasma and neonatal plasma in 10 women at term, irrespective of the P doses administered and the time elapsed (up to 15 h) between administration of the last P dose and delivery. The ratios of cord plasma to simultaneous maternal plasma levels for propranolol and its major metabolites (mean±SD) were: propranolol 0.32±0.17, propranolol glucuronide 0.86±0.36, 4-hydroxypropranolol 1.4±1.0, 4-hydroxypropranolol glucuronide 0.71±0.45 and naphthoxylactic acid 3.0±1.6. P binding in cord plasma at delivery was 67.2±3.9% (mean±SD) which was significantly less (‘t’=13.4,df=13,p〈0.001) than the P binding in maternal plasma at delivery (87.5±1.6%, mean±SD). The plasma protein binding (mean±SD) of naphthoxylactic acid in cord plasma (98.6±0.2%) was significantly greater (‘t’=3.808,df=4,p〈0.02) than the naphthoxylactic acid binding in maternal plasma at delivery (97.6±0.4%). When the simultaneous concentrations of P and naphthoxylactic acid in maternal and cord plasma are compared in conjunction with protein binding and ionic effects, it would seem that metabolism of P does occur in the placental/foetal unit.
    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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