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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 42 (1992), S. 559-560 
    ISSN: 1432-1041
    Keywords: Mefloquine ; Thai subjects ; pharmacokinetics ; Primaquine ; drug interaction ; adverse effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
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  • 2
    ISSN: 1432-1041
    Keywords: Insulin ; Fosinopril ; insulin sensitivity ; glucose tolerance ; lipoproteins ; ACE inhibition ; normal humans ; blood pressure ; adverse effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effect of the new ACE-inhibitor, fosinopril, on insulin sensitivity (SI), glucose homoeostasis and lipid profile has been examined in 24 young, healthy, normotensive men. SI, fasting plasma glucose and insulin, serum total triglycerides (Tg) and lipoprotein cholesterol (C) fractions, and ACE activity were assessed after subjects had taken placebo for 1 week and after 3 further weeks either on placebo (12 subjects) or fosinopril 20 mg daily (12 subjects), administered in a doubleblind, randomized order. Measurements were made after 3 days on a standard diet (2500 kcal/d, 45% carbohydrates, 40% fat and 15% proteins) and after an over-night fast. Compared with control values at the end of the runin placebo phase, fosinopril reduced plasma ACE activity (from 106 to 24 nmol·ml−1·min−1), Significantly increased plasma potassium and lowered upright systolic blood pressure. It also improved the k-value of the glucose disappearance rate after glucose load (from −1.70 to −1.88%·min−1) and tended to increase SI slightly although not significantly (from 10.2 to 12.0·10−4·min−1·μU−1·ml−1). Fasting plasma glucose, insulin, serum total, high-, low-, and very-low density lipoprotein cholesterol fractions and total triglycerides were unchanged following fosinopril and placebo. The findings indicate that in healthy lean humans, ACE inhibition with fosinopril is neutral with regard to lipoprotein and carbohydrate metabolism, and that it may slightly enhance cellular glucose disposal. This calls for further evaluation in individuals at high risk of developing insulin resistance and in patients with impaired insulin sensitivity related to hypertension, obesity, decreased glucose tolerance and diabetes mellitus.
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  • 3
    Electronic Resource
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    European journal of clinical pharmacology 42 (1992), S. 43-46 
    ISSN: 1432-1041
    Keywords: Isradipine ; hypertension ; platelet function ; prostaglandin system ; adverse effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effect of treatment for eight weeks with isradipine 1.25 mg twice daily for 4 weeks and thereafter 2.5 mg twice daily for 4 weeks on ex vivo platelet function was investigated in 10 male hypertensive patients, aged 51 (6.1) y. Systolic and diastolic blood pressure, platelet aggregation in response to ADP, serum thromboxane B2 and β-thromboglobulin levels were significantly decreased at rest before exercise ergometry, during exercise and at rest after exercise. The platelet count, platelet sensitivity and the plasma levels of 6-oxo-prostaglandin F1α were not affected by isradipine. It is concluded that a compound that lowers blood pressure and inhibits platelet activation may be of clinical benefit in the routine treatment of hypertension.
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  • 4
    ISSN: 1432-1041
    Keywords: Skin atrophy ; Prednicarbate cream ; ultrasound ; betamethasone-17-valerate-cream ; clobetasol-17-propionate cream ; adverse effects ; skin atrophy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The atrophogenic potential of medium-potent topical glucocorticoids is still controversial. In a double-blind controlled trial 24 healthy volunteers either applied 0.25% prednicarbate cream or the corresponding vehicle to one and 0.1% betamethasone-17-valerate cream or 0.05% clobetasol-17-propionate cream to the other forearm twice daily. Skin thickness was regularly assessed during the six week period of application and for further three weeks thereafter, using both the B- and A-mode of a 20 MHz ultrasound scanner. Both betamethasone-17-valerate and clobetasol-17-propionate cream significantly reduced skin thickness as compared to cream base while prednicarbate cream did not. Given that 0.1% betamethasone-17-valerate- and 0.25% prednicarbate cream are reported to be about equipotent in the treatment of atopic eczema the latter preparation shows an increased ratio between its desired anti-inflammatory and its unwanted atrophogenic effect.
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  • 5
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    European journal of clinical pharmacology 42 (1992), S. 171-174 
    ISSN: 1432-1041
    Keywords: Quinine ; Malaria ; pharmacokinetics ; red blood cells ; plasma ; saliva ; adverse effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of quinine has been studied in ten healthy adult Africans after intravenous infusion and oral ingestion of a 500 mg dose. Blood and saliva samples were collected over 48 h and quinine in plasma, red cells and saliva was determined by HPLC. Quinine was rapidly and almost completely absorbed after an oral dose, with absorption half-life of 0.53 h, a tmax of 1–3 h and a bioavailability of 88%. Analysis of the i. v. data gave an apparent volume of distribution of 3.6 1·kg−1 and a plasma clearance of 0.19 l·kg−1·h−1. The concentration-time curves for plasma, red cells and saliva had declining phases were approximately parallel, giving a similar half-life that in all three media. The half-lives after the i. v. infusion also did not different from those after oral administration. The dose was well tolerated by both methods of administration.
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  • 6
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    European journal of clinical pharmacology 42 (1992), S. 203-207 
    ISSN: 1432-1041
    Keywords: Nicorandil ; pharmacokinetics ; angina pectoris ; uraemia ; adverse effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of oral nicorandil 20 mg 12 hourly for 9 doses was evaluated in 21 hospitalized patients with angina pectoris due to coronary heart disease and with normal and impaired renal function. Patients were divided into 3 groups based on creatinine clearance (CLCr): GROUP I (n=6) 〉 80 ml/min, GROUP II (n=8) 20–80 ml/min, and GROUP III (n=7) 〈 20 ml/min. After the first dose, the total clearance of nicorandil (CL) value did not change with increasing renal failure and so was not dependent on creatinine clearance. After the last dose CL was 51 l·h−1 in Group I, 44 l·h−1 in Group II and 56 l·h−1 in Group III, and it was not related to creatinine clearance. The percentage of the dose excreted in the urine was 0.4%. No significant difference was noted in any of the other pharmacokinetic parameters examined in the three groups, not even on comparing values obtained on the first and last days of treatment. The findings suggest that there is no need to change the dose of nicorandil in subjects with different degrees of renal failure.
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  • 7
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    European journal of clinical pharmacology 42 (1992), S. 95-99 
    ISSN: 1432-1041
    Keywords: Ofloxacin ; Haemodialysis ; ofloxacin metabolites ; pharmacokinetics ; multiple doses ; dosage selection ; renal failure ; adverse effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary 7 patients with end-stage renal disease on regular haemodialysis were treated orally with a loading dose of 200 mg ofloxacin and multiple maintenance doses of 100 mg per 24 h for 10 days. The pharmacokinetics of ofloxacin and its metabolites were studied at the end of the treatment period. Plasma and dialysate concentrations of ofloxacin and ofloxacin metabolites were measured by HPLC. Peak (3.1 mg·1−1) and trough levels (1.6 mg·1−1) and the AUC of ofloxacin were comparable to the values in healthy volunteers given 300 to 400 mg ofloxacin p.o. The mean half-life, determined in the dialysis-free interval (t1/2β) and during the haemodialysis session (t1/2HD), was 38.5 h and 9.9 h, respectively. Extrarenal clearance (32.7 ml·min−1) was unchanged as compared to that reported in healthy volunteers after a single dose of ofloxacin. The fractional removal by haemodialysis amounted to 21.5%. Two metabolites, ofloxacin-N-oxide and demethyl-ofloxacin, were detected in plasma. Despite prolonged t1/2β of both metabolites (66.1 and 50.9 h) and multiple doses of ofloxacin the peak concentrations of the metabolites reached only 14% and 5% of that of the parent drug, respectively. It is concluded that in patients on regular haemodialysis treatment the dosage adjustment employed resulted in safe and therapeutically favourable plasma concentrations. The observed accumulation of ofloxacin metabolites does not appear to have any toxic or therapeutic significance.
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  • 8
    ISSN: 1432-1041
    Keywords: Methotrexate ; non-steroidal anti-inflammatory drugs (NSAIDs) ; interaction ; disposition ; adverse effects ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary We have studied the pharmacokinetics of methotrexate in patients with rheumatoid arthritis concurrently treated with choline magnesium trisalicylate, ibuprofen, naproxen, or a non-NSAID analgesic (control treatment). The apparent systemic clearance of methotrexate was significantly reduced by all three treatments. Trisalicylate and ibuprofen both significantly reduced methotrexate renal clearance, but only the trisalicylate significantly displaced methotrexate from protein, increasing the fraction unbound by 28%. These data show that NSAIDs can affect the disposition of methotrexate, possibly increasing the potential for toxicity and necessitating dosage adjustments. However, large inter-subject variability precludes specific dosage recommendations.
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  • 9
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    European journal of clinical pharmacology 43 (1992), S. 567-569 
    ISSN: 1432-1041
    Keywords: Mefloquine ; Tetracycline ; Thai subjects ; Thai subjects ; drug interaction ; pharmacokinetics ; adverse effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The kinetics of a single oral dose of mefloquine given either alone or with tetracycline has been studied in 20 healthy Thai male volunteers. There was a significantly higher maximum whole blood mefloquine concentration after coadministration with tetracycline (1600 vs 1160 ng · ml−1), as well as a significantly reduced terminal half-life (14.4 vs 19.3 days), mean residence time (11.9 vs 16.0 days) and volume of distribution at steady state (13.3 vs 19.91 · kg−1). Although there was no significant change in the AUC from zero time to infinity, the AUC from zero time to 7 days was significantly increased by tetracycline (6.18 vs 4.76 μg · ml−1 · day). The changes in mefloquine disposition after tetracycline treatment are probably due to a reduction in enterohepatic recycling. The initial increase in mefloquine AUC without an apparent increase in side-effects suggests that this combination may have a place in the treatment of multi-drug resistant falciparum malaria.
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  • 10
    ISSN: 1432-1041
    Keywords: Theophylline, Nocturnal hypoxaemia ; chronic obstructive pulmonary disease ; sleep study ; static charge sensitive bed ; adverse effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effect of a 24-h controlled-release (CR) preparation of theophylline (Th) on nocturnal arterial oxygen saturation (SaO2) and sleep quality has been evaluated in 7 patients with advanced chronic obstructive pulmonary disease (COPD) in a double-blind cross-over experiment; median values: age 61 y; PaO2 8.0 kPa; PaCO2 5.8 kPa. During treatment with 450–900 mg Th in the evening, morning plasma drug levels ranged from 5.2–12.9 µg·ml−1. During Th and placebo treatment, the median evening FEV1 was 0.45 l and 0.46 l, respectively, and the morning FEV1 was 0.53 l and 0.41 l. Sleep was monitored by whole-night polysomnographic recording of oximetric SaO2, airflow, respiratory and body movements (static charge sensitive bed), eye movements and submental electromyogram. There was no significant difference between Th and placebo in sleep quality. Th treatment was associated with a marginal improvement in nocturnal oxygenation in most of the patients; the average nocturnal SaO2 ranged from 84.4%–92.8% during Th and from 82.2–90.5% during placebo treatment, respectively. Only in the morning, during the last 2 h in bed, was the slight difference in SaO2 statistically significant in favour of Th. It is concluded that a moderate dose of CR-theophylline did not alter the sleep quality or substantially improve nocturnal oxygenation in patients with advanced COPD and mild to moderate day-time hypoxaemia.
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  • 11
    ISSN: 1432-1041
    Keywords: Felodipine ; Hypertension ; dosage regimen ; extended release tablet ; adverse effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The blood pressure lowering capacity of felodipine administered either as extended release tablets once or twice daily or as plain tablets twice daily has been compared in a double-blind, three-way cross-over study in 16 hypertensive patients. All the patients were on long-term treatment with 10 or 20 mg felodipine daily and other antihypertensive therapy (mainly beta-blockers) was allowed if it was kept unchanged. Non-invasive blood pressure and heart rate recordings were obtained throughout 24 hour periods using an Accutracker ambulatory system. The 24 h mean systolic and diastolic blood pressures after extended release tablets o.m. did not differ significantly from those after extended release tablets b.d. or plain tablets b.d. There was a tendency for the extended release tablets given o.m. to reduce blood pressure somewhat more in the morning, and for the extended release tablets b.d. to reduce blood pressure more during the night than the other treatments. Mean 24 h heart rate after all treatments was comparable. Manual recordings confirmed these results. Blood pressure was well-controlled throughout the 24 h period by all three treatments. The extended release tablets tended to give less extreme plasma concentrations of felodipine. This may be of value for patients with adverse vasodilator effects. For a majority of hypertensive patients the adequacy of blood pressure control and the simplicity of once daily dosing will favour the extended release tablet given once daily.
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  • 12
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    European journal of clinical pharmacology 42 (1992), S. 593-598 
    ISSN: 1432-1041
    Keywords: Metamizole ; Furosemide ; prostaglandins ; drug interaction ; adverse effects ; pharmacokinetics ; pharmacodynamics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetic and pharmacodynamic interactions between metamizole (dipyrone) and furosemide were investigated in 9 of 12 healthy female subjects able to complete the study. They received oral metamizole 3×1 g for 3 days or placebo (cross-over) and on the last day of both study periods furosemide 20 mg IV. On the last two days a balanced sodium diet (120 mEq) and on Day 3 an oral water load (600 ml) were given. Metamizole significantly inhibited basal urine flow, whereas the fractional excretion of sodium and chloride and the 12 h-GFR remained unchanged. Metamizole significantly reduced furosemide clearance (175 vs 141 ml · min−1), furosemide-stimulated plasma renin activity (1.42 vs 0.79 ng AI · ml−1 · h−1) and the urinary excretion of prostacyclin metabolites and of prostaglandin F2α (by 70–81%). The renal clearance and terminal half-life of furosemide, peak renal chloride and volume excretion were unchanged. Thus, metamizole did not interact with the renal excretion and the diuretic effect of furosemide, although prostaglandin synthesis was significantly reduced.
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  • 13
    ISSN: 1432-1041
    Keywords: Nitrendipine ; Bisoprolol ; Hypertension ; self-measured blood pressure ; diurnal variation ; adverse effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In a double-blind, placebo-controlled study the antihypertensive efficacy and tolerability of a single morning dose of either 10 mg bisoprolol (n=26) or 20 mg nitrendipine (n=27) were investigated. Blood pressure was measured by three techniques: (1) Casual blood pressure 24 h after the dose; (2) ambulatory 24-h whole-day monitoring; and (3) self-recorded blood pressure in the morning 24 h after the dose (6–8 a.m.) and in the evening (6–8 p.m.). After 4 weeks of therapy bisoprolol had produced a highly significant reduction in blood pressure as assessed by casual, ambulatory day- and night-time monitoring, and self-measured morning and evening readings. Bisoprolol was significantly more effective than nitrendipine, which did not induce a significant reduction in the ambulatory night-time recordings. Whole-day ambulatory blood pressure profiles showed an antihypertensive effect of bisoprolol throughout the entire 24-h period. 24-h blood pressure curves after nitrendipine demonstrated a markedly shorter duration of action, with no reduction in early morning blood pressure. Adverse effects and tolerability of the two drugs were comparable. The average changes in systolic and diastolic blood pressure after bisoprolol and nitrendipine in 2-h periods of ambulatory monitoring (6–8 a.m. and 6–8 p.m.) and self-measured blood pressure (6–8 a.m. and 6–8 p.m.) showed a good agreement between ambulatory and self-measured blood pressure determinations with no significant difference between the methods. The results show that 24 h antihypertensive efficacy was more pronounced for bisoprolol than for nitrendipine at the doses studied. Further, self-measured blood pressures at home were suitable for accurate estimation of the 12-h and 24-h antihypertensive efficacy of the two drugs. The methodological findings of this study have important implications for further pharmacological trials investigating the duration of action of antihypertensive drugs.
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  • 14
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    European journal of clinical pharmacology 43 (1992), S. 527-531 
    ISSN: 1432-1041
    Keywords: Calcitonin ; Colonic administration ; Bioavailability ; pharmacokinetics ; pharmacodynamics ; adverse effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Human calcitonin (hCT) injected into the lumen of the descending colon of normal human subjects was absorbed within minutes and could be recognized intact in plasma as shown by RIA in combination with reverse-phase HPLC. The absorption was low and variable, with bioavailabilities ranging from 0.01% to 2.7% relative to intravenously administered hCT (area under the concentrationtime curve). With intravenous hCT serum calcium was lowered and the fractional urinary excretion of calcium, phosphorus, sodium and chloride was significantly stimulated. With the intracolonic hCT, the fractional urinary excretions of calcium, sodium and chloride were also marginally stimulated relative to intracolonic vehicle (placebo). In conclusion, hCT is absorbed intact from the colon, but the bioavailability is low and highly variable.
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  • 15
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    European journal of clinical pharmacology 43 (1992), S. 85-88 
    ISSN: 1432-1041
    Keywords: Hypertension ; Carvedilol ; chronic renal failure ; pharmacokinetics ; adverse effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetic and acute systemic haemodynamic effects of a single oral dose of 50 mg carvedilol has been studied in 24 hypertensive patients with chronic renal failure. The patients were stratified into 3 groups according to the creatinine clearance: I 51–90 ml · min−1; II 26–50 ml · min−1; III 4–25 ml · min−1. The area under plasma level time curve AUC, the elimination half-life t/12, the maximum plasma concentration Cmax, the time to peak concentration tmax were not significantly different between groups, whereas the amount of unchanged drug or metabolite excreted in urine Ae and the renal clearance CLR of carvedilol and its metabolites M2, M4, M5 were significantly decreased in Group III. Blood pressure and heart rate decreased in all 3 groups of patients after acute administration of 50 mg carvedilol. Mild adverse effects were reported in 6 patients. Despite a decrease in the renal clearance of carvedilol and of its metabolites with decreasing kidney function, its main pharmacokinetic parameters remained unchanged. The present results suggest that the dose of carvedilol need not be reduced in hypertensive patients with chronic renal failure.
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  • 16
    ISSN: 1432-1041
    Keywords: Paracetamol ; Analgesia ; plasma concentration ; sustained release ; dose-effect relation ; laser induced pain ; adverse effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The analgesic efficacy of single doses of immediate release paracetamol 500 mg and 1000 mg, sustained release paracetamol 2000 mg, and placebo was evaluated over a 12 h period in 10 healthy volunteers. The efficacy was related to the concurrent plasma concentrations of paracetamol. Experimental pain was induced by brief cutaneous application of argon laser pulses, and the analgesic effect was assessed as change in pricking pain threshold. Both 0.5 g and 1.0 g immediate release paracetamol had an analgesic effect superior to that of placebo from 1 to 5 h after administration. Peak analgesia was reached after 2 h. No difference was found in the analgesic effect of the two dosages. Sustained release paracetamol was not significantly superior to placebo at any time. The plasma concentration of paracetamol had peaked in the 1 h sample after of the immediate release tablet. The peak plasma concentration was reached 3–4 h after 2.0 g sustained release paracetamol. It is not known why the sustained release formulation did not produce any detectable analgesia. It is proposed, that the rate of increase in the plasma concentration of paracetamol might be important in the alleviation of acute (laser-induced) pain.
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  • 17
    ISSN: 1432-1041
    Keywords: Dihydropyridine ; Felodipine ; availability ; flavonoids ; dietary interaction ; pharmacokinetics ; pharmacodynamics ; adverse effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effect of drinking grapefruit juice on the acute pharmacokinetic and haemodynamic actions of the dihydropyridine calcium antagonist felodipine given as a 5 mg plain tablet has been studied in nine, healthy, middle-aged males. Compared to water, grapefruit juice caused an increase in Cmax from mean 6 to 16 nmol · l−1, and in the AUC from 23 to 65 nmol · h · l−1. The change in AUC corresponded to an increase in the systemic availability of felodipine from 15 to 45%, assuming no change in its clearance. This change was probably caused by inhibition of the oxidation of felodipine to the inactive dehydrofelodipine by flavonoids in grapefruit juice. The interaction with grapefruit juice is believed to be a class effect for the dihydropyridines, as oxidation of the dihydropyridine ring to the corresponding pyridine derivative is a major metabolic route for all these drugs. The higher plasma concentrations of felodipine taken with grapefruit juice resulted in a greater change in blood pressure measured in the morning 3 h after dosing (−9%) than did water (0%).
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  • 18
    ISSN: 1432-1041
    Keywords: Nifedipine ; omeprazole ; absorption ; gastric pH ; pharmacokinetic ; drug interaction ; adverse effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effects of single dose (20 mg) and short-term (20 mg/day for 8 days) oral treatment with omeprazole on the pharmacokinetics and effects of oral nifedipine (10 mg capsule) and on gastric pH have been investigated in a randomized, double-blind, placebo-controlled cross-over study in 10 non-smoking healthy male subjects. The single dose of omeprazole had no significant effect on any pharmacokinetic parameter of nifedipine, nor on gastric pH, or blood pressure or heart rate. Short-term omeprazole treatment increased the AUC of nifedipine by 26% (95% confidence interval 9–46%), but all other pharmacokinetic parameters of nifedipine, including elimination half-life, Cmax, tmax, and recovery of the main urinary metabolite, were not significantly changed. The median gastric pH during the absorption phase of nifedipine was increased by short-term omeprazole (pH 4.2) compared to placebo treatment (pH 1.4). Blood pressure and heart rate did not differ between treatments. The interaction between nifedipine and omeprazole is not likely to be of major clinical relevance.
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  • 19
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    European journal of clinical pharmacology 42 (1992), S. 347-348 
    ISSN: 1432-1041
    Keywords: Neuroleptics ; Debrisoquine oxidation ; haloperiodol ; phenothiazines ; adverse effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
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  • 20
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    European journal of clinical pharmacology 42 (1992), S. 371-374 
    ISSN: 1432-1041
    Keywords: Ambenonium chloride ; Myasthenia gravis ; dietary effect ; serum concentration ; adverse effects ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Influence of food on the serum concentration and kinetics ambenonium chloride (AMBC) has been examined in thirteen patients with myasthenia gravis (MG). Mean serum concentrations and Cmax during fasting were higher than those in the non-fasting state. The AUC (0–3 h) was also about four-times larger. The drug effects versus the serum concentration were observed to be anti-clockwise or clockwise. The effective range of the Cmax varied between patients. The unexpected increase in Cmax led to adverse muscarinic actions of AMBC, when the condition was changed from the non-fasting to the fasting state. It is recommended that the dose be changed during non-fasting treatment when adjusting the optimum regimen for patients myasthenia gravis. Patients must be advised to keep to the dosing and dietary schedule in order to avoid unexpected adverse actions to AMBC.
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  • 21
    ISSN: 1432-1041
    Keywords: Lovastatin ; Pravastatin ; Hypercholesterolaemia ; cholestyramine ; lipoproteins ; apolipoproteins ; adverse effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effects of the HMG CoA reductase inhibitors lovastatin and pravastatin on serum lipids, lipoproteins and apolipoproteins have been studied in 35 patients with primary hypercholesterolaemia. LDL cholesterol was lowered to the same extent by both agents compared on a mg basis of each drug per day. HDL cholesterol was increased by lovastatin but not by pravastatin. The reduction in serum triglycerides, VLDL triglycerides and VLDL cholesterol was more pronounced after lovastatin than pravastatin. After 1 year the effect of combined treatment with 40 mg pravastatin and 8 g cholestyramine on the reduction in LDL cholesterol (−39%) in 13 patients was comparable to that of 80 mg lovastatin plus 8 g cholestyramine (−40%) in 12 patients with identical baseline values. Differences were also found in the effects of the combination therapy with the two drugs on HDL cholesterol, serum triglycerides, VLDL triglycerides, VLDL cholesterol, and apolipoproteins.
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  • 22
    ISSN: 1432-1041
    Keywords: Nicardipine ; Hypertension ; ambulatory blood pressure ; adverse effects ; hydrochlorothiazide ; captopril
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The antihypertensive efficacy of sustained-release nicardipine compared to placebo as third-line therapy has been assessed by ambulatory blood pressure monitoring in severly hypertensive patients with clinically unsatisfactory blood pressure control on 50 mg hydrochlorothiazide o.d. and 75 mg captopril b.d. Forty-two patients, 31 m and 11 f, with supine diastolic blood pressure 95–115 mm Hg after a 4 week run-in period on open hydrochlorothiazide and captopril, were randomly allocated to sustained-release nicardipine 45–60 mg/d or placebo. At a visit to the clinic blood pressure and heart rate were measured 12 h after the evening dose by a trained observer unaware of the treatment. Twenty-four hour ambulatory monitoring was performed at the end of baseline and after 8 weeks of blinded medication. There was no significant change in BD at the visit or on ambulatory monitoring in the placebo treated patients. In contrast, nicardipine produced a significant reduction in both blood pressures without affecting heart rate. Nicardipine also decreased the mean 24-h blood pressure by 14/10 mm Hg in patients whose clinical hypertension had been confirmed by ambulatory blood pressure monitoring but by only 3/2 mm Hg in ambulant patients who were normotensive on two-drug therapy. One patient experienced an episode of severe symptomatic hypotension while on nicardipine. Otherwise, the numbers and percentages of patients from each group reporting adverse experiences were similar. It is concluded that nicardipine appears to be an effective antihypertensive agent when used as third line therapy with diuretics and angiotensin converting enzyme inhibitors in patients with severe hypertension. In addition, since 40% of such patients already on two drug therapy were found to have a normal ambulatory blood pressure, the results reinforce the value of ambulatory monitoring in distinguishing hypertensives in whom more aggressive treatment may not by justified.
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  • 23
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    European journal of clinical pharmacology 43 (1992), S. 209-210 
    ISSN: 1432-1041
    Keywords: Moxonidine ; Hydrochlorothiazide ; pharmacokinetics ; drug interaction ; steady-state ; healthy volunteers ; adverse effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Type of Medium: Electronic Resource
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