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  • 1
    Electronic Resource
    Electronic Resource
    The pharmacokinetics of captopril and captopril disulfide conjugates in uraemic patients on maintenance dialysis: Comparison with patients with normal renal function (1987)
    Springer
    European journal of clinical pharmacology 32 (1987), S. 267-271 
    Details
    ISSN: 1432-1041
    Keywords: captopril ; uraemia ; captopril disulfide ; dialysis ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary We have measured the plasma concentrations of captopril and total disulfide conjugates of captopril after a 50 mg oral dose in 6 uraemic patients on maintenance dialysis and in 8 hypertensive subjects with normal renal function. The mean peak plasma concentration of captopril was 2.5 times higher (0.447 µg·ml−1 vs 0.181 µg·ml−1) and the concentrations of the disulfides 4 times higher (3.62 µg·ml−1 vs 0.924 µg·ml−1) in the uraemic patients. Moreover captopril disulfide conjugates in the uraemic subjects reached peak concentrations at 8 h after the dose and subsequently felt. The apparent plasma half-time was 46±19 h. Only 15% of these conjugates were removed by dialysis. This marked accumulation of captopril conjugates was associated with a sustained fall in both systolic and diastolic blood pressures. In uraemic patients the mean maximum reduction in systolic and diastolic blood pressures were 37±7 mmHg and 24±9 mmHg respectively, occurring 6 h after the dose, compared with 8±7 and 8±1 mmHg respectively at 30 min in normal renal function patients. These results are consistent with the results of animal experiments, which show that captopril disulfides can be converted back to free captopril and can contribute to the antihypertensive effect of the drug. They provide a reationale for reducing the dose and frequency of administration of captopril in patients with significant renal impairment.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00607574
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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
    Pharmacokinetic and pharmacodynamic studies of oral clonidine in normotensive subjects (1982)
    Springer
    European journal of clinical pharmacology 23 (1982), S. 1-5 
    Details
    ISSN: 1432-1041
    Keywords: clonidine ; noradrenaline ; pharmacokinetics ; arterial blood pressure ; plasma concentration
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of clonidine and its relation to blood pressure response and side effects were studied after single oral doses of 75 µg, 150 µg and 250 µg in normotensive subjects. Following oral administration, the drug was absorbed rapidly after an initial lag time of 19–22 min and peak levels were reached between 2.4 and 2.9 h. Sampling over 48 h was necessary for accurate estimation of pharmacokinetic parameters. Post-peak plasma concentration declined in a monoexponential manner and the half-life of the elimination phase ranged from 9.0 to 15.1 h. Maximum plasma concentration (Cmax) and area under curve (AUC) increased proportionally with increasing doses. Clonidine produced significant reductions in the pulse rate and a dose dependent decrease in blood pressure. Clonidine (150 µg) also produced significant reductions in plasma catecholamine levels.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01061368
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  • 4
    Electronic Resource
    Electronic Resource
    Adrenaline and phenylethanolamine-N-methyltransferase in rat medullary and anterior hypothalamic-preoptic nuclei (1979)
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 33 (1979), S. 0 
    Details
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1471-4159.1979.tb09926.x
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  • 5
    Electronic Resource
    Electronic Resource
    RELATIONSHIP BETWEEN SYSTEMIC AND CORONARY VASCULAR RESPONSES TO DIGOXIN AND CONCURRENT DRUG THERAPY WITH VERAPAMIL/β-ADRENOCEPTOR ANTAGONISTS IN HUMANS (1990)
    Oxford, UK : Blackwell Publishing Ltd
    Clinical and experimental pharmacology and physiology 17 (1990), S. 0 
    Details
    ISSN: 1440-1681
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: 1. In 24 patients who were undergoing coronary arteriography for the assessment of ischaemic heart disease, the relationship between the systemic and coronary vascular responses to acute intravenous digoxin administration (500 μg) and concurrent drug therapy with the calcium antagonist verapamil (group I) or a β-adrenoceptor antagonist (group II) or neither of these agents (group III) was examined.2. Systemic vascular resistance (SVR) tended to rise rapidly after digoxin injection in patients in groups II and III, and tended to decline initially in patients in group I; however, these differences were not statistically significant (variance ratio [VR] = 0.77).3. No significant differences were observed in coronary vascular responses to acute digoxin administration between the three groups of patients (VR = 0.34).4. For the entire group of 24 patients, no statistically significant digoxin-induced effects on resistance could be demonstrated in either the systemic or coronary circulations, although in individual patients vasoconstrictor effects were observed.5. We conclude that acute intravenous administration of digoxin does not consistently cause systemic or coronary vasoconstriction in patients with ischaemic heart disease. Variability in vasomotor responses to digoxin is not clearly related to concurrent drug therapy with verapamil or a β-adrenoceptor antagonist. The observation that systemic vascular resistance tends to increase in the first few minutes after digoxin injection should be addressed in future studies.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1440-1681.1990.tb01344.x
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  • 6
    Electronic Resource
    Electronic Resource
    THE METABOLIC FATE OF LEVODOPA IN MAN AND ANIMALS (1974)
    Oxford, UK : Blackwell Publishing Ltd
    Clinical and experimental pharmacology and physiology 1 (1974), S. 0 
    Details
    ISSN: 1440-1681
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: SUMMARY 1. Administration of levodopa in man and rats resulted in a large increase in the daily excretion in the urine of dopamine and its metabolites, but not of noradrenaline.2. In the rat administration of levodopa substantially increased dopamine concentrations in the heart and brainstem, but noradrenaline concentrations were decreased.3. It is suggested that administration of levodopa leads to dopamine production in concentrations high enough to saturate intraneuronal uptake, so that the main uptake is extraneuronal, hence the major products are dopamine and its metabolites.4. The lack of evidence of increased noradrenaline synthesis in the presence of diminished tissue levels of noradrenaline suggests that either the intraneuronal vesicular uptake or the β-hydroxylation of dopamine may be an important regulating step in the synthesis of noradrenaline.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1440-1681.1974.tb00556.x
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  • 7
    Electronic Resource
    Electronic Resource
    COMPARISON OF THE PHARMACOKINETICS AND PHARMACODYNAMICS OF PERINDOPRIL, CILAZAPRIL AND ENALAPRIL (1992)
    Oxford, UK : Blackwell Publishing Ltd
    Clinical and experimental pharmacology and physiology 19 (1992), S. 0 
    Details
    ISSN: 1440-1681
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: 1. The pharmacokinetic and pharmacodynamic responses to enalapril, perindopril and cilazapril have been studied in essential hypertensives (2, 4 and 8 mg perindopril and 2.5 mg cilazapril, single dose and steady state) and normotensive volunteers (10 mg enalapril, single dose).2. Plasma levels of the active diacid compounds reached similar peaks after single dose administration of the drugs. However, perindoprilat levels persisted for 5 days whereas cilazaprilat levels were not detectable beyond 12 h.3. The higher levels of perindoprilat were associated with a greater inhibition of plasma angiotensin-converting enzyme (ACE) activity in both acute and steady state studies.4. The potency of the active diacids in inhibiting plasma ACE activity was perindoprilat 〉 cilazaprilat 〉 enalaprilat.5. There was a close relationship between plasma concentration, ACE inhibition and blood pressure decrease. Although both cilazapril and perindopril administration reduced blood pressure in hypertensive subjects, only perindopril exerted 24 h blood pressure control at the doses used.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1440-1681.1992.tb02811.x
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  • 8
    Electronic Resource
    Electronic Resource
    HAEMODYNAMIC EFFECTS OF A SINGLE LOW DOSE OF PRAZOSIN IN PATIENTS WITH CHRONIC CONGESTIVE CARDIAC FAILURE CORRELATIONS WITH PHARMACOKINETICS (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 haemodynamic effects and pharmacokinetics of a single orally administered dose of 0.5 mg of prazosin have been compared in six patients with stable severe congestive cardiac failure. Administration of prazosin induced significant decreases in mean pulmonary capillary wedge pressure (from 27.5, s.e.m.=4.5 to 19.4, s.e.m.=5.1 mmHg; P〈0.001), mean arterial blood pressure (from 94.5, s.e.m.=6.0 to 85.4, s.e.m.=5.0 mmHg; P〈0.01), and systemic vascular resistance (from 1690, s.e.m.=360 to 1420, s.e.m.=200 dyn. s/cm5; P〈0.05) and a rise in cardiac index from 1.98 (s.e.m.=0.07) to 2.28 (s.e.m.=0.16) litres/min per m2 (P〈0.05). There was a non-significant fall in heart rate.2. Pharmacokinetic analysis revealed maximum plasma prazosin concentrations of 4.1 (s.e.m.=1.4) ng/ml, occurring 2.1 (s.e.m.=0.4) h after drug ingestion. The mean elimination half-life was 5.1 (s.e.m.=0.8) h, which is longer than that found in our previous studies in normal subjects. There was considerable interindividual variation in peak plasma prazosin concentrations, elimination half-life and area under the concentration-time curve. While mean maximal haemodynamic effects of prazosin occurred at similar times to the peak plasma concentration of the drug, there was no significant correlation between the extent of haemodynamic response and individual pharmacokinetic parameters.3. It is concluded that significant and potentially beneficial haemodynamic effects occur with the initial administration of 0.5 mg oral doses of prazosin in patients with stable congestive cardiac failure and it is suggested that in many patients little advantage will be achieved with higher initial doses.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1440-1681.1984.tb00234.x
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  • 9
    Electronic Resource
    Electronic Resource
    EFFECTS OF ANTIHYPERTENSIVE DRUGS ON CARDIOVASCULAR RISK FACTORS (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. Large scale studies have failed to show a substantial benefit of antihypertensive therapy on the incidence of ischaemic heart disease.2. This may be due to adverse effects of antihypertensive drugs on plasma lipoproteins or because of failure to adequately manage other risk factors for atherogenesis.3. Hypercholesterolaemia is very common in patients receiving antihypertensive therapy, and is difficult to manage successfully using existing treatment strategies.4. The achievement of a reduction in mortality and morbidity from ischaemic heart disease amongst hypertensive patients represents a major challenge. Success will probably depend upon the development of adequate methods of lowering plasma cholesterol levels.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1440-1681.1988.tb01062.x
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  • 10
    Electronic Resource
    Electronic Resource
    ACUTE AND CHRONIC PHARMACOKINETIC STUDIES OF SLOW RELEASE KETOPROFEN (ORUVAIL) IN RHEUMATOID ARTHRITIS (1986)
    Oxford, UK : Blackwell Publishing Ltd
    Clinical and experimental pharmacology and physiology 13 (1986), S. 0 
    Details
    ISSN: 1440-1681
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: 1. Slow release preparations of non-steroidal anti-inflammatory drugs are used to simplify dose regimes in the treatment of rheumatoid arthritis with the aim of improving patients compliance. This study examines the acute and chronic pharmacokinetics of slow release ketoprofen in 13 rheumatoid patients with a mean age of 59.8 years.2. Pharmacokinetic parameters following the first dose including Tmax which was 6.92 h (s.e.m. = 0.80), Cmax 3.87 μg/ml (s.e.m. = 0.54), apparent half-life 8.8 h (s.e.m. = 1.0) and AUC 41.92 μg.h/ml (s.e.m. = 4.02) were not significantly different from those following the last dose after 3 months of chronic treatment, when these were Tmax 6.38 h (s.e.m. = 0.84) Cmax 3.57 μg/ml (s.e.m. = 0.33) apparent half-life 8.8 h (s.e.m. = 1.1) and AUC 43.18 μg.h/ml (s.e.m. = 5.34) respectively. These results show that no accumulation of ketoprofen occurred with chronic treatment.3. Clinical assessments were performed in an open design and showed significant improvement in pain, articular index, grip strength and duration of morning stiffness when these parameters were compared to treatment with paracetamol during an initial washout. The drug was well tolerated although there was a trend for the haemoglobin to fall and this parameter should be monitored during therapy with ketoprofen.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1440-1681.1986.tb00938.x
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