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  • 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
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 36 (1989), S. 283-290 
    ISSN: 1432-1041
    Keywords: ibuprofen ; enantiomers ; stereoselective protein binding ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary We have developed a novel and reproducible method for determining the plasma protein binding of the two ibuprofen enantiomers in the presence of each other. The method involves the use of radiolabelled racemic ibuprofen, equilibrium dialysis, derivatization of the enantiomers to diastereomeric amides, high-performance liquid chromatography, and radiochemical analysis. We have determined the plasma protein binding of R(−)- and S(+)-ibuprofen in 6 healthy male volunteers after the oral administration of 800 mg racemic ibuprofen. The mean time-averaged percentage unbound of the R(−)-enantiomer, 0.419 was significantly less than that of the S(+)-enantiomer, 0.643, consistent with stereoselective plasma protein binding. The percentage unbound of each ibuprofen enantiomer was concentration-dependent over the therapeutic concentration range and was influenced by the presence of its optical antipode.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-1041
    Keywords: aspirin ; salicylic acid ; low-dose aspirin pharmacokinetics ; platelet function
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of low-dose aspirin and the resulting salicylic acid were studied in 6 healthy volunteers. Each received a single 50-mg dose of (1) oral modified release capsules, (2) oral solution and (3) intravenous solution. The volunteers also received 50 mg modified release capsules daily for 6 days to determine the effect on collagen, ADP and arachidonate induced platelet aggregation and thromboxane production, and to compare the pharmacokinetics after repeated dosing with the parameters obtained after the single dose. The formulation and route of administration profoundly influenced several pharmacokinetic parameters for aspirin: the maximum concentration (Cmax, ng·ml−1) was 221 and 191 after modified release for single and chronic dosing respectively, 1323 after the oral solution and 6000 after intravenous injection; the time to achieve this maximum concentration (tmax, h) was 3.42 and 3.02 after modified release for single and chronic dosing respectively, and 0.29 after the oral solution; the area under the plasma drug concentration versus time curve (AUC, µg·h·ml−1) was 0.38 and 0.27 after modified release single and chronic dosing respectively, 0.68 after the oral solution and 1.57 after intravenous injection. The elimination of aspirin after the two solutions was at least biphasic. The terminal phase rate constant ranged from 1.52 h−1 after intravenous injection to 1.88 h−1 after the oral modified release form. The absorption of the oral forms of aspirin was complete as reflected by the total recovery of the doses as salicylic acid in urine. The pharmacokinetic parameters for salicylic acid showed similar tmax and Cmax for the oral solution and intravenous injection but, as for aspirin, Cmax was least and tmax greatest when the modified release form was used. After 7 days of modified release aspirin platelet aggregation and thromboxane formation in response to collagen and arachidonate were markedly inhibited. There was no inhibition of ADP-induced aggregation, but thromboxane production in response to ADP was abolished.
    Type of Medium: Electronic Resource
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  • 5
    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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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 31 (1986), S. 235-237 
    ISSN: 1432-1041
    Keywords: cimetidine ; tolbutamide ; pharmacokinetic interaction ; drug metabolism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary We have investigated the influence of cimetidine on the disposition of tolbutamide in 7 healthy subjects, who received 250 mg tolbutamide daily for 4 days followed by the concomitant intake of cimetidine 400 mg twice daily for a further 4 days. Cimetidine had no effect on the disposition of tolbutamide, including the unbound hydroxylation clearance rate (324 ml·min−1, tolbutamide alone; 316 ml·min−1, tolbutamide plus cimetidine). The total urinary recovery of carboxy- and hydroxy-tolbutamide metabolites was 85.7±20.3% of the dose when tolbutamide was given alone and 78.9±14.3% when given with cimetidine. This lack of a pharmacokinetic interaction suggests selectivity of cimetidine-induced inhibition of Phase I drug oxidation.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 39 (1990), S. 457-461 
    ISSN: 1432-1041
    Keywords: Vancomycin ; drug utilization ; drug usage evaluation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A prospective, two-phase, drug utilization review (DUR) was performed at the Royal Adelaide Hospital (RAH) to determine the extent and pattern of vancomycin use. For all patients commencing oral or parenteral vancomycin, treatment indication, route of administration, duration of therapy, results of culture and sensitivity tests, adverse drug reactions and results of therapeutic drug level monitoring were recorded. Vancomycin courses were classified as being for therapy or prophylaxis and compared with predetermined audit criteria to assess appropriateness of use. During the 8 week initial phase, data on 62 treatment courses in 59 patients were recorded, 50% for therapy and 50% for prophylaxis. Sixty four percent were classified as inappropriate, occurring in 32% of therapeutic courses and 97% of those for prophylaxis. During the 10 week re-evaluation, conducted 10 months later, data for 43 treatment courses in 43 patients were reviewed, 42% for therapy and 58% for prophylaxis. Sixty five percent were inappropriate occuring in 17% of therapeutic courses and 100% of the prophylactic courses. When compared with the initial phase, the re-evaluation demonstrated a decrease in the empirical use of vancomycin in the combination treatment of neutropaenic fever and also in the duration of vancomycin use for surgical prophylaxis. During both study phases, criteria contraventions were mostly due to inappropriate indication or duration of therapy. The cost of inappropriate vancomycin use was reduced by over 50% between survey phases, from $Aus11,500 or 55% of total vancomycin cost during the initial phase to $Aus3,600 or 25.7% during the re-evaluation. The most effective of the remedial strategies implemented after the initial phase was direct consultation with prescriber groups. The effectiveness of this DUR has provided the basis for an ongoing DUR programme at the RAH which has been met with general acceptance by hospital clinicians and administrators.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1432-1041
    Keywords: salicyl phenolic glucuronide ; rheumatoid arthritis ; aspirin ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of salicyl phenolic glucuronide (SPG) and other salicylic acid (SA) metabolites were studied at three aspirin dosage regimens in eight patients with rheumatoid arthritis. Each patient received 1, 2 and 4 g enteric coated aspirin (ASA) daily in ascending order. At the end of each 2-week dosage period, plasma and urine were collected over a dosage interval for the estimation of various pharmacokinetic parameters. With increasing ASA dosage, mean clearance of SA to SPG was approximately constant (1.8±0.3, 1.7±0.2, and 1.5±0.2 ml/min at 1, 2 and 4 g/day, respectively) when related to plasma concentrations of total SA. The percentage of the ASA dosage recovered in urine as SPG increased from 5.2±1.1 to 7.1±1.1 to 10.5±1.7 at 1, 2 and 4 g/day, respectively. It was concluded, however, that the conversion of SA to SPG is saturable, since the mean clearance of SA to SPG decreased when calculated with respect of the plasma concentration of unbound SA (13.4±1.6, 11.0±1.4, and 6.6±1.9 ml/min at 1, 2 and 4 g/day, respectively). The kinetics of the formation and excretion of salicylurate and the excretion of gentisate were similar to those found in previous studies.
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 41 (1991), S. 379-382 
    ISSN: 1432-1041
    Keywords: Codeine ; paracetamol ; codeine-6-glucuronide ; pharmacokinetics ; metabolism ; partial clearance ; drug interaction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Plasma and urine concentrations of codeine and its measurable metabolites were determined by HPLC in six healthy subjects after a single 30 mg oral dose of codeine either alone or after 7 doses of 1 g paracetamol 8 hourly. After codeine alone, the t1/2 (h), AUC (μmol·l−1·h) and CLR (ml·min−1) for codeine were 2.2, 0.81, and 252 respectively. These were not significantly altered by paracetamol: 2.2, 0.84, and 291 respectively. For codeine-6-glucuronide the values were 2.4, 22.0, and 29.7 respectively. These were not significantly different from those after codeine plus paracetamol: 2.4, 21.9, and 39.6. There were no significant differences between the two treatments in the apparent partial clearances (ml·min−1) of codeine to morphine (88 codeine alone, 70 codeine plus paracetamol), to norcodeine (71 codeine alone, 88 codeine plus paracetamol), and to codeine-6-glucoronide (820 codeine alone, 1022 codeine plus paracetamol). The urinary excretion of codeine-6-glucuronide, morphine, norcodeine, and codeine were not significantly different between the two treatments.
    Type of Medium: Electronic Resource
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  • 10
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    Journal of Chromatography B: Biomedical Sciences and Applications 183 (1980), S. 175-184 
    ISSN: 0378-4347
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
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