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  • 1
    Electronic Resource
    Electronic Resource
    Effect of cimetidine and ranitidine on carbamazepine and sodium valproate pharmacokinetics (1984)
    Springer
    European journal of clinical pharmacology 27 (1984), S. 341-343 
    Details
    ISSN: 1432-1041
    Keywords: cimetidine ; ranitidine ; carbamazepine ; sodium valproate ; pharmacokinetics ; drug metabolism ; inhibition
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of a single oral dose (400 mg) of carbamazepine and sodium valproate were compared in peptic ulcer patients before and after four weeks of a therapeutic course of either cimetidine (1 g/day, n=6 subjects) or ranitidine (300 mg/day, n=6 subjects). There was a small (up to 20%) but statistically significant decrease in oral clearance of carbamazepine after cimetidine treatment. A similar fall in sodium valproate clearance in five cimetidine-treated patients was accompanied by a significantly prolonged elimination half-life. No such trends were demonstrated during ranitidine treatment. Since both anticonvulsants are partly metabolized by hepatic mixed function oxidases, an inhibition by cimetidine at this level may be responsible for the observed impairment of clearance. Thus a potentially important clinical interaction may occur in patients taking anticonvulsants and cimetidine concurrently.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00542172
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  • 2
    Electronic Resource
    Electronic Resource
    Single and chronic dose pharmacokinetic studies of sodium valproate in epileptic patients (1979)
    Springer
    European journal of clinical pharmacology 16 (1979), S. 23-29 
    Details
    ISSN: 1432-1041
    Keywords: valproate ; epilepsy ; pharmacokinetics ; drug interaction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In four refractory epileptic patients, peak plasma levels of sodium valproate occurred within 1.5 to 3 h after a single oral dose of valproate and the decline in plasma levels followed a monoexponential course with a t1/2 of 11.4 ± 0.1 h. The mean value for apparent volume of distribution was 0.176 ± 0.013 l/kg and for total plasma clearance 0.0106 ± 0.0009 l/h/kg. Steady state plasma levels were predicted using the method of superposition utilizing pharmacokinetic parameters determined following a single dose of valproate and were 78–123% of the predicted values for two patients receiving valproate alone, and 37–64% of the predicted values for the two patients receiving carbamazepine in addition to valproate. In a further group of 20 patients the mean daily doses of valproate for 8 patients receiving valproate alone (25.4 ± 4.9 mg/kg) was significantly less than those for the 12 patients receiving concomitant anticonvulsant therapy (41.6 ± 12.3 mg/kg) (p〈0.005). In addition, the steady state predose plasma levels of valproate were significantly higher in the valproate alone patients (90.3 ± 8.7 µg/ml) compared to the patients receiving additional anticonvulsants (75.3 ± 13.8 µg/ml) (p〈0.01). The higher dose requirements of valproate and lower predose and steady state plasma levels for those patients on multiple anticonvulsants indicate an interaction between valproate and other anticonvulsants.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00644962
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  • 3
    Electronic Resource
    Electronic Resource
    The possible effect of long-term high plasma levels of phenytoin on mortality after acute myocardial infarction (1973)
    Springer
    European journal of clinical pharmacology 5 (1973), S. 138-144 
    Details
    ISSN: 1432-1041
    Keywords: Phenytoin ; plasma level ; myocardial infarction ; treatment
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In a group of patients studied for 12 months after myocardial infarction plasma levels of phenytoin were measured whilst the patients received phenytoin 300–400 mg per day or placebo therapy. Two sub-groups of patients treated with phenytoin were identified, based on the steady state level of plasma phentyoin concentration. Patients who had achieved phenytoin plasma concentrations of 10 µg/ml or above, had a significantly lower mortality than patients who had plasma concentration below this level or than patients treated with placebo. Ventricular premature beats occurred significantly less often in the phenytoin treated group than among the comparative group of patients. The significance of these findings is discussed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00564893
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  • 4
    Electronic Resource
    Electronic Resource
    RELATIONSHIP BETWEEN THE DOSE-RESPONSE EFFECTS OF DIAZEPAM AND CLOBAZAM ON ELECTROENCEPHALOGRAPHIC PARAMETERS AND ON KINDLED AMYGDALOID SEIZURE ACTIVITY IN RATS (1988)
    Oxford, UK : Blackwell Publishing Ltd
    Clinical and experimental pharmacology and physiology 15 (1988), S. 0 
    Details
    ISSN: 1440-1681
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: 1. The possibility that the anticonvulsant activity of the benzodiazepines, diazepam and clobazam, is related to changes in EEG parameters, particularly β activity, was investigated in amygdaloid kindled rats.2. The effects of diazepam (1, 2, 4, 8 and 16 μmol/kg), administered intraperitoneally (i.p.), clobazam (1, 2, 4, 8, 16 and 32 μmol/kg, i.p.) or vehicle (dimethyl sulfoxide) on the cortical EEG of amygdaloid kindled rats were quantitated for 15 min using computerized period amplitude analysis. Immediately afterwards, the amygdala was stimulated and the after-discharge duration (AD) and the seizures stage (SS) were determined.3. The equivalent percentage time (EPT) of the diazepam-treated group was decreased in the θ band (4–8 Hz) and increased in the α (8–12 Hz) and first six β (12–36 Hz) bands. The mean peak amplitude (MPA) was increased in the α (8–12 Hz) and all seven β bands (12–40 Hz). Clobazam increased the EPT and MPA in the α (8–12 Hz) and all seven β (12–40 Hz) bands. The MPA was also increased by clobazam in the θ (4–8 Hz) band.4. Diazepam reduced both the AD and SS of the kindled seizures at doses of 4, 8 and 16 μmol/kg, whereas clobazam was anticonvulsant at doses of 16 and 32 μmol/kg. The reduction in both AD and SS correlated with increases in the EPT and MPA in the first β (12–16 Hz) band in the diazepam-treated group and in the first four β (12–28 Hz) bands in the clobazam-treated group.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1440-1681.1988.tb01015.x
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  • 5
    Electronic Resource
    Electronic Resource
    EFFECT OF INCREASED BILE FLOW AND BILE ACID SECRETION ON THE HEPATIC ELIMINATION OF SODIUM VALPROATE IN THE CAT (1984)
    Oxford, UK : Blackwell Publishing Ltd
    Clinical and experimental pharmacology and physiology 11 (1984), S. 0 
    Details
    ISSN: 1440-1681
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: 1. The effect of increased bile flow and hepatic bile acid flux on the systemic clearance and hepatic elimination of intravenously administered sodium valproate was studied in the bile fistula cat. Taurochenodeoxycholic acid (TCDC), tauro-3α, 7β-dihydroxy-12-keto-5β-cholanoic acid (T12K), SC-2644, and secretin were infused intravenously to vary bile flow and biliary bile acid secretion. Control animals were infused with 0.15 mol/l NaCl.2. Less than 1% of the drug administered to controls appeared as unchanged valproate in the bile over 6 h. Although SC-2644, T12K, and secretin significantly increased biliary excretion of valproate, it did not exceed 2% of the intravenous dose. Biliary clearance was directly related to the rate of bile flow, but not to the bile acid flux.3. By contrast, 18–19% of the dose appeared in bile as metabolite in controls, and none of the choleretic agents significantly increased this percentage. As a result, systemic clearance of valproate was unaltered.4. We conclude that the movement of unchanged valproate into bile is consistent with a process of simple diffusion. The fact that choleretic agents do not increase metabolite excretion into bile suggests that metabolite formation may be the rate-limiting step in the hepatic elimination of valproate, rather than transport and excretion of metabolites into bile.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1440-1681.1984.tb00269.x
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  • 6
    Electronic Resource
    Electronic Resource
    GAS CHROMATOGRAPHIC MEASUREMENT OF PLASMA LEVELS OF SODIUM VALPROATE: TENTATIVE THERAPEUTIC RANGE OF A NEW ANTICONVULSANT IN THE TREATMENT OF REFRACTORY EPILEPTICS (1978)
    Oxford, UK : Blackwell Publishing Ltd
    Clinical and experimental pharmacology and physiology 5 (1978), S. 0 
    Details
    ISSN: 1440-1681
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: 1. A precise and rapid gas chromatographic method for the measurement of plasma sodium valproate concentrations is presented.2. The extraction is a single step procedure, and is reproducible and linear throughout the concentration range encountered.3. Clinical evaluation of the drug is presented in eighteen epileptics on the basis of the percentage of days on which subjects had seizures before and after sodium valproate therapy.4. A tentative therapeutic range for sodium valproate is presented on the basis of plasma levels and therapeutic effect.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1440-1681.1978.tb00653.x
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  • 7
    Electronic Resource
    Electronic Resource
    Renal clearance of methotrexate in man during high-dose oral and intravenous infusion therapy (1981)
    Springer
    Cancer chemotherapy and pharmacology 6 (1981), S. 59-64 
    Details
    ISSN: 1432-0843
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The renal excretion and clearance of methotrexate (MTX) following high-dose (800 mg) therapy followed by folinic acid rescue was studied in 12 patients (2 female, 10 male): the mean age was 49.3±5.5 (SE), weight 68.6±3.9 (SE) and body surface area 1.8±0.1 m2. Plasma and urine were collected over 154 h at intervals of 2–24 h, and the collection times, volume, and pH of urine samples recorded. Total MTX concentrations in urine and plasma were measured by the highly specific competitive protein-binding assay method. Plasma and urinary creatinine levels were measured on an SMA-12 autoanalyser. The renal clearance of MTX was calculated for each urine collection period. Following oral administration, clearance values during the first 6 h were high at 257±8.3 (ml/min), followed by a trough in clearance of 27.9±4.2 (ml/min) in the 20- to 30-h period. This was followed by a secondary rise of MTX renal clearance to 180.4±14.6 ml/min during the 68- to 84-h period and again to 84.9±17.1 ml/min between 84 and 112 h. In the last two periods it rose to 209±57.9 ml/min. Similar fluctuations were seen following IV administration. The changes in clearance were statistically significant at the P〈0.005 level. It is suggested that high concentrations of MTX in the renal tubules result in inhibition of carrier protein synthesis, leading to a fall in active tubular secretion. When MTX concentrations fall the tubular cell recovers and a secondary rise in renal clearance occurs, leading to cyclical changes in MTX elimination.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00253011
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