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Biomedical subjects

A Markham

Publications and source records attributed to A Markham.

At least 55 records · Page 3Linked to original sources
PubMed1998

Telmisartan.

Telmisartan is a nonpeptide angiotensin II receptor antagonist which selectively and insurmountably inhibits the angiotensin II AT1 receptor subtype without affecting other receptor systems involved in cardiovascular regulation. Oral telmisartan dose-dependently reduced blood pressure (BP) in various animal models of hypertension. In transgenic rats, telmisartan reduced cardiac hypertrophy and glomerulosclerosis. When administered at dosages of 40 to 160 mg once daily to patients with mild to moderate hypertension, telmisartan significantly reduced systolic and diastolic BP compared with placebo and was at least as effective as atenolol 50 or 100 mg and lisinopril 10 to 40 mg. One study showed telmisartan 80 mg/day to be more effective than enalapril 20 mg/day. In 2 studies that used ambulatory BP monitoring, once daily telmisartan provided better control of diastolic BP for the full dosing interval than losartan potassium 50 mg or amlodipine 5 or 10 mg. In a single study in patients with severe hypertension, a telmisartan-based regimen had antihypertensive efficacy similar to that of an enalapril-based regimen. Telmisartan had a tolerability profile similar to that of placebo in clinical studies.

Angiotensin Receptor Antagonists↗
PubMed1998

Theophylline. A review of its potential steroid sparing effects in asthma.

UNLABELLED: Theophylline is generally considered to be a bronchodilatory drug. However, recent pharmacodynamic studies indicate that it has anti-inflammatory effects. It reduced eosinophil survival rates in vitro, and reduced eosinophil accumulation in bronchial tissue in patients with atopic asthma. Theophylline has also been shown to reduce T cell proliferation and accumulation. These changes were mirrored by improved pulmonary function in patients with asthma in studies that evaluated this parameter. Three randomised double-blind studies have evaluated the potential role of theophylline as an anti-inflammatory treatment in patients with asthma not controlled by low doses of inhaled corticosteroids. Patients were randomised to receive low dose theophylline (400 to 750 mg daily) plus low dose inhaled corticosteroids, or an increased dose of inhaled corticosteroids. Clinical pulmonary function improved to the same or a greater extent in patients who received low dose inhaled corticosteroids plus theophylline than in those treated with high dose inhaled corticosteroids plus placebo. Where reported, the dosages of theophylline used in these studies resulted in serum theophylline concentrations of approximately 9 to 10 mg/L. Approximate monthly costs were provided in one study: these were $60 (year and currency not specified) for theophylline plus budesonide 800 micrograms/day, compared with $100 for budesonide 1600 micrograms/day, and $155 for a regimen of budesonide 800 micrograms/day and salmeterol 100 micrograms/day. CONCLUSIONS: Low dose theophylline has been shown to reduce requirements for inhaled corticosteroid therapy in patients with asthma and may reduce overall treatment costs.

Adrenal Cortex Hormones↗
PubMed1997

Lisinopril. A review of its pharmacology and clinical efficacy in elderly patients.

Lisinopril, the lysine analogue of enalaprilat, is a long-acting angiotensin converting enzyme (ACE) inhibitor which is administered once daily by mouth. The efficacy of lisinopril in reducing blood pressure is well established in younger populations, and many trials now show it to be effective in lowering blood pressure in elderly patients with hypertension. In comparative and non-comparative clinical trials, 68.2 to 89.1% of elderly patients responded (diastolic pressure < or = 90 mm Hg) to > or = 8 weeks' lisinopril treatment. Age-related differences in antihypertensive efficacy do not appear to be clinically significant, and dosages effective in elderly patients tend to range from 2.5 to 40 mg/day. Dosages usually need to be lower in patients with significant renal impairment. In congestive heart failure, lisinopril 2.5 to 20 mg/day increases exercise duration, improves left ventricular ejection fraction and has no significant effect on ventricular ectopic beats. It is similar in efficacy to enalapril and digoxin and similar or superior to captopril on most end-points. Data from the GISSI-3 post-myocardial infarction trial show that lisinopril reduced mortality and left ventricular dysfunction when given for 42 days starting within 24 hours of the onset of infarction symptoms. Results at 6 weeks and 6 months were similar in elderly and younger patients. Elderly patients, however, among other subgroups, exhibited a strong reduction in risk of low ejection fraction after treatment (-25.5%). Economic studies suggest that lisinopril is cost saving compared with other ACE inhibitors in some markets. When given according to the GISSI-3 protocol, lisinopril appears to be one of the less expensive of the successful ACE inhibitor regimens for acute myocardial infarction. In other trials, patients with diabetic nephropathy and hypertension improved or did not deteriorate during lisinopril treatment. Blood pressure was controlled and reductions or trends towards reductions in albuminuria were observed. These reductions were similar to those in diltiazem, nifedipine and verapamil recipients, and greater than those in patients receiving atenolol. Lisinopril appears to reduce mortality in diabetic patients after myocardial infarction and may also improve neuropathy associated with diabetes. Lisinopril is well tolerated and the profile of adverse events seen is typical of ACE inhibitors as a class. There is a tendency for more elderly than younger patients to discontinue treatment, but this trend is not clearly related to the incidence of adverse events in these age groups. Drug interactions occur with few other agents and are usually clinically significant only between lisinopril and either diuretics or lithium. Lisinopril is, thus, an effective treatment for elderly patients with hypertension, congestive heart failure and acute myocardial infarction and has shown promising benefits in patients with diabetic nephropathy.

Aged↗
PubMed1997

Sparfloxacin. A review of its antibacterial activity, pharmacokinetic properties, clinical efficacy and tolerability in lower respiratory tract infections.

Sparfloxacin is a fluoroquinolone antibacterial agent with activity against a broad range of Gram-negative and Gram-positive organisms including Streptococcus pneumoniae, one of the main pathogens in community-acquired pneumonia. In this infection, sparfloxacin has shown efficacy similar to that of amoxicillin, erythromycin, roxithromycin, amoxicillin/clavulanic acid and amoxicillin plus ofloxacin, producing clinical cure rates of 80 to 84% assessed by intention-to-treat analyses in European or multinational trials. US studies showed similar results for sparfloxacin to those for erythromycin and cefaclor. Sparfloxacin was also as effective as all other comparator drugs in patients with other lower respiratory tract infections, usually acute exacerbations of chronic obstructive pulmonary disease (COPD). The profile of adverse effects for sparfloxacin is generally similar to that of other quinolones: gastrointestinal discomfort and CNS effects are the most common in clinical trials. Sparfloxacin causes fewer gastrointestinal disturbances than agents such as amoxicillin and erythromycin and doses not interact with theophylline, an important consideration when treating patients with respiratory disease. Its long elimination half-life permits once-daily dosage regimens. On the other hand, there are infrequent reports of prolonged QTc interval (3% increase) during sparfloxacin therapy. Photosensitivity occurs more frequently than with the other fluoroquinolones (2% of patients in an ongoing postmarketing study and 7.9% of those in US trials), and requires ongoing surveillance. In summary, the good activity of sparfloxacin against S. pneumoniae and other respiratory pathogens supports its use in lower respiratory tract infections, particularly community-acquired pneumonia. Its profile of good efficacy, once-daily dosage, good gastrointestinal tolerability and lack of interaction with theophylline are advantageous, but clinicians and patients must be alert to the possibility of photosensitivity reactions. On this basis, sparfloxacin, when appropriately prescribed, can provide the clinician with a useful alternative treatment option for these common infections.

Animals↗
PubMed1997

Fludarabine. An update of its pharmacology and use in the treatment of haematological malignancies.

Fludarabine is an antineoplastic agent which has been studied in patients with a variety of lymphoproliferative malignancies. Clinical evidence from comparative studies in chronic lymphocytic leukaemia (CLL) suggests that fludarabine is at least as effective as CAP (cyclophosphamide, doxorubicin and prednisone) or CHOP (cyclophosphamide, vincristine, doxorubicin and prednisone) in previously treated or chemotherapy-naive patients and significantly more effective than chlorambucil in terms of response rate and duration and survival in chemotherapy-naive patients. Promising results have also been reported with fludarabine-based combination therapy in the treatment of patients with CLL. In addition, sequential therapy with fludarabine and cytarabine has demonstrated good efficacy in the treatment of acute leukaemias, as has fludarabine monotherapy and combination therapy in low grade non-Hodgkin's lymphoma. A favourable cytoreductive response has been reported in patients with lymphoplasmacytoid lymphoma and in a smaller number of patients with cutaneous T cell lymphomas, CLL of T cell origin or prolymphocytic leukaemia. Recent data also support the use of fludarabine, either as a component of a nonmyeloablative conditioning regimen or in the attainment of minimal residual disease, in patients undergoing peripheral blood stem cell or bone marrow transplantation. The tolerability profile of fludarabine is similar to that of CAP, with the most common adverse events being granulocytopenia, thrombocytopenia, anaemia and infection. Alopecia and nausea/vomiting appear to be less frequent with fludarabine therapy than with CAP although the development of immune cytopenias is more frequent with fludarabine. Severe neurotoxicity has been reported with fludarabine but this is mostly confined to the use of high doses. Clinical experience therefore indicates that fludarabine is an effective and generally well-tolerated antineoplastic agent for the second-line treatment of advanced CLL. Recent data from comparative studies also support the earlier use of fludarabine in the treatment of chemotherapy-naive patients with CLL. Furthermore, results of available studies are increasingly highlighting an important future role for fludarabine in the treatment of acute leukaemias and low grade NHL and possibly other lymphoproliferative disorders, particularly when used as a component of combination chemotherapy.

Antineoplastic Agents↗
PubMed1997

Troglitazone.

Troglitazone decreases insulin resistance (improves insulin sensitivity), which results in reduced plasma glucose and insulin levels in patients with non-insulin-dependent diabetes mellitus (NIDDM). Risk factors for cardiovascular disease such as elevated proinsulin and triglyceride levels are also reduced by troglitazone. In clinical trials, troglitazone 200 to 800 mg daily (alone or in combination with other oral antidiabetic agents or insulin) reduced plasma or serum glucose levels and glycosylated haemoglobin compared with both baseline and placebo in patients with NIDDM refractory to other oral antidiabetic agents (usually sulphonylureas). Troglitazone was generally well tolerated in clinical trials. In patients in the US, the incidence of adverse events in troglitazone recipients was similar to that in placebo recipients.

Animals↗
PubMed1997

Valsartan. A review of its pharmacology and therapeutic use in essential hypertension.

Valsartan competitively and selectively inhibits the actions of angiotensin II at the AT1 receptor subtype which is responsible for most of the known effects of angiotensin II. In clinical trials in patients with mild to moderate essential hypertension valsartan was as effective as losartan, lisinopril, enalapril, amlodipine and hydrochlorothiazide. Addition of the latter reduced blood pressure in patients who did not respond sufficiently to valsartan monotherapy. Preliminary data also suggest valsartan may be effective in patients with severe essential hypertension. The drug was as effective as lisinopril as treatment for mild to moderate essential hypertension in patients with renal insufficiency and did not worsen renal function. Headache, dizziness and fatigue were the most common adverse events in placebo-controlled studies; the incidence of these adverse events was not significantly different between placebo and valsartan recipients. Compared with ACE inhibitors, valsartan was associated with a significantly lower incidence of dry cough. Thus, valsartan is an effective treatment for mild to moderate essential hypertension and may be particularly useful in patients who experience persistent cough during ACE inhibitor therapy.

Antihypertensive Agents↗
PubMed1997

Ibutilide. A review of its pharmacological properties and clinical potential in the acute management of atrial flutter and fibrillation.

Ibutilide is the first 'pure' class III antiarrhythmic drug to become available. Its predominant action is prolongation of the myocardial action potential duration. This appears to be achieved by a unique ionic mechanism of action that involves activation of a late inward sodium current and possibly blockade of the rapidly activating component of the cardiac delayed rectifier potassium current. Intravenous ibutilide 0.01 to 0.025 mg/kg or 1 to 2 mg successfully converted atrial flutter or fibrillation to sinus rhythm in 33 to 49% of patients in 2 placebo-controlled trials involving 439 patients with sustained arrhythmia. In a third trial in 300 patients who developed atrial flutter or fibrillation after cardiac surgery, ibutilide 2 mg successfully converted the arrhythmia in 57% of patients. The mean times to conversion were < or = 30 minutes in these trials. In 3 comparative trials, ibutilide was significantly more effective than racemic sotalol or procainamide in terminating atrial flutter or fibrillation. The pretreatment duration of the arrhythmia is an important predictor of the success of ibutilide treatment; the greatest conversion rates are achieved when the arrhythmia is of recent onset (i.e. < or = 30 days' duration). Ibutilide is more effective in terminating atrial flutter than atrial fibrillation. Adverse events associated with ibutilide are predominantly cardiovascular. Sustained polymorphic ventricular tachycardia developed in 1.7%, and non-sustained polymorphic ventricular tachycardia in 2.7%, of 586 patients treated with ibutilide in clinical trials. However, no proarrhythmia-related deaths have been reported with the use of ibutilide. The drug has minimal haemodynamic effects and is associated with few noncardiovascular adverse events. Thus, ibutilide is a useful agent for the pharmacological cardioversion of recent-onset atrial fibrillation or flutter, provided that adequate steps are taken to monitor for proarrhythmic events. The drug causes few noncardiovascular adverse events and has minimal haemodynamic effects. Furthermore, it appears to be more effective than procainamide (especially in patients with atrial flutter) and racemic sotalol.

Anti-Arrhythmia Agents↗
PubMed1997

Fenoldopam: a review of its pharmacodynamic and pharmacokinetic properties and intravenous clinical potential in the management of hypertensive urgencies and emergencies.

Fenoldopam is a dopamine agonist that causes peripheral vasodilation via stimulation of dopamine 1 (D1) receptors. The efficacy of an intravenous infusion of fenoldopam in decreasing blood pressure in patients with a hypertensive urgency, including patients who developed hypertension after coronary artery bypass graft surgery, and in a small number of patients with hypertensive emergency, is similar to that of sodium nitroprusside. However, unlike sodium nitroprusside, fenoldopam also increases renal blood flow and causes diuresis and natriuresis. There is no evidence of rebound hypertension after stopping the infusion. As the tolerability profile of fenoldopam is generally similar to that of sodium nitroprusside, fenoldopam appears to be an effective alternative to sodium nitroprusside in the immediate treatment of patients who develop severe hypertension and in whom oral treatment is not practical. Fenoldopam may be particularly useful in patients who develop hypertension after coronary artery bypass graft surgery, but further studies are required to confirm its role in hypertensive emergency.

Antihypertensive Agents↗
PubMed1997

Clopidogrel.

Clopidogrel is a thienopyridine that irreversibly inhibits platelet aggregation by selectively binding to adenylate cyclase-coupled ADP receptors on the platelet surface. In animal models, clopidogrel reduced the formation of both arterial and venous thrombi. After oral administration, clopidogrel is rapidly absorbed and undergoes metabolic activation in the liver. The principal circulating metabolite is SR 26334, an inactive carboxylic acid derivative. The active metabolite is not yet known. Findings of a large, well controlled study of clopidogrel versus aspirin in patients with atherosclerotic vascular disease (CAPRIE study) indicate that clopidogrel has superior efficacy in terms of prevention of ischaemic stroke, myocardial infarction and vascular death. Clopidogrel-treated patients experienced less frequent gastrointestinal upset, abnormal liver function and gastrointestinal haemorrhage than patients who received aspirin, but more frequent rash and diarrhoea. Neutropenia and thrombocytopenia occurred rarely and at similar rates in both groups.

Animals↗
PubMed1997

Mibefradil. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy in the management of hypertension and angina pectoris.

Mibefradil belongs to a new class of calcium antagonists, the tetralol derivatives. It selectively blocks T-type calcium channels in contrast to other calcium antagonists which block only L-type channels. Mibefradil relaxes coronary arteries without suppressing myocardial contractility and causes a dose-related decrease in heart rate. When given orally once daily to patients with hypertension mibefradil produces a dose-related decrease in blood pressure which is sustained for 24 hours and improves exercise performance in patients with stable angina pectoris. In patients with generally mild to moderate hypertension oral mibefradil was superior to nifedipine SR and diltiazem CD, tended to be more effective than nifedipine GITS and had similar efficacy to amlodipine. Mibefradil 50 to 100mg once daily also has antianginal and anti-ischaemic effects. The drug improves the duration of symptom-limited exercise and the time to onset of ischaemia, and reduces the frequency of anginal attacks and consumption of nitroglycerin. Its efficacy is similar to that of diltiazem and tends to be greater than that of amlodipine in patients with stable angina. Mibefradil is generally well tolerated and is associated with a lower incidence of leg oedema than amlodipine and nifedipine. Thus, mibefradil is a calcium antagonist with a predictable cardiovascular profile, which, on the basis of available clinical data, is an effective alternative to other drugs widely used in the treatment of hypertension and stable angina pectoris.

Angina Pectoris↗
PubMed1997

Irbesartan. A review of its pharmacodynamic and pharmacokinetic properties and therapeutic use in the management of hypertension.

Irbesartan inhibits the activity of angiotensin II (AII) via specific, selective noncompetitive antagonism of the AII receptor subtype 1 (AT1) which mediates most of the known physiological activities of AII. In patients with mild to moderate hypertension, once daily administration of irbesartan 150 or 300 mg, with or without adjunctive antihypertensive agents, provides effective 24-hour BP control. Irbesartan reduced BP to a similar extent to enalapril and atenolol and to a significantly greater extent than losartan. The combination of irbesartan and hydrochlorothiazide resulted in additive antihypertensive effects. The drug is effective in the elderly and dosage adjustment is not required in these patients or in those with renal or hepatic failure. Preliminary studies evaluating the efficacy of irbesartan in patients with heart failure have produced encouraging results. Irbesartan is very well tolerated and neither the frequency nor the pattern of adverse events differed from those seen in placebo recipients, although headache was significantly more frequent with the latter. Similarly, the incidence of adverse events did not differ significantly between irbesartan and enalapril in patients who received either drug as monotherapy. Headache, upper-respiratory tract infection and musculoskeletal pain were the most common complaints. Thus, irbesartan is an effective therapy for patients with mild to moderate hypertension and had an adverse event profile similar to that of placebo in clinical trials. On this basis it would appear to be an effective therapeutic option in this indication.

Angiotensin II↗
PubMed1997

Danaparoid. A review of its pharmacology and clinical use in the management of heparin-induced thrombocytopenia.

Danaparoid, a low molecular weight heparinoid consisting of a mixture of heparan, dermatan and chondroitin sulfates, has well established antithrombotic activity. The drug has a high antifactor Xa to antifactor IIa (thrombin) activity ratio, a low tendency to cause bleeding and minimal effects on the fibrinolytic system. Danaparoid has a low cross-reactivity rate with heparin-associated antiplatelet antibodies (0 to 20%; mean approximately 10%). This represents a significant advantage over low molecular weight heparins (LMWHs) as a potential replacement agent for unfractionated heparin (UFH) in patients with immune-mediated (type II) heparin-induced thrombocytopenia (HIT). In a worldwide compassionate-use programme involving a total of 667 patients with HIT to date, 93% of danaparoid treatment courses were considered to be successful. Thrombocytopenia resolved in 91% of episodes. In a multicentre randomised comparative trial of danaparoid and dextran in patients with HIT plus thrombosis (HITT), significantly more danaparoid than dextran recipients had resolution of thromboses, and an effective clinical response was achieved in significantly more danaparoid recipients. Results of a retrospective case-controlled study of danaparoid and ancrod in patients with HITT showed significantly fewer new or progressive thromboses with danaparoid. In the compassionate-use programme, danaparoid was associated with a mortality rate of 10.4% during treatment (up to 3.5 years) and 7.8% during the follow-up period (3 months). 14 of 114 deaths during the follow-up period were considered to be related to danaparoid therapy. A mortality rate of 23.5% was reported in patients accepted for but not treated with, danaparoid. Mortality rates with danaparoid, ancrod and dextran in the comparative studies were similar (7, 11 and 12%, respectively). Severe bleeding was reported in 3.1% of patients in the compassionate-use programme, persistent or recurrent thrombocytopenia in 2.6% and new thromboembolic events/extension of existing thrombosis in 1.7%. The incidence of bleeding was similar with danaparoid and dextran in a comparative trial. Although in vitro cross-reactivity does not always translate into clinical cross-reactivity, testing is currently recommended, when possible, before initiation of danaparoid therapy. Thus, danaparoid appears to be an effective and well tolerated replacement agent for UFH in many patients with HIT who require further anticoagulation. The drug has low cross-reactivity with HIT-associated antibodies. Further comparative trials are needed to confirm these promising findings.

Blood Coagulation↗
PubMed1996

Selenium homeostasis in the central nervous system of the rat.

These experiments have investigated selenium movement between blood and CNS in anaesthetised rats. Each animal was surgically anaesthetised and the left femoral blood vessels cannulated for blood withdrawal and solute infusion. Each rat received 75-selenium as sodium selenite infused in normal saline and experiments lasted between 5 minutes and 5 hours during which blood samples were periodically taken. At termination, the CNS was removed, regionally dissected and analysed with the plasma samples for 75-Se radioactivity by gamma-counting. Data were analysed by graphical analysis. Results showed unidirectional uptake of 75-Se into the CNS and regional differences were not found except for the hypothalamus. On average the CNS influx rate constant (Kin) was about 7 +/- 1 x 10(-5) ml/min/g. Data suggest that the 75-Se most likely entered the CNS as a free ionic form.

Animals↗
PubMed1996

Clarithromycin and omeprazole as helicobacter pylori eradication therapy in patients with H. pylori-associated gastric disorders.

Helicobacter pylori is susceptible to many antibacterial drugs in vitro but has proved difficult to eradicate in vivo. The macrolide clarithromycin has good activity against H. pylori in vitro and has demonstrated the highest eradication rate for any antibacterial monotherapy in vivo. However, it is clear that antibacterial monotherapy is not a sufficiently effective treatment for patients with H. pylori infection. The suggestion that high intragastric acidity impairs the action of antibacterial drugs led to the evaluation of combination H. pylori eradication regimens including H+,K+-ATPase inhibitors and antibacterial drug(s) with or without bismuth compounds. Noncomparative studies evaluating the efficacy of dual therapy with clarithromycin plus omeprazole in patients with H. pylori infection have reported eradication rates of between 58 and 83% > or = 4-weeks after therapy. In comparative studies, clarithromycin plus omeprazole was at least as effective as amoxicillin plus omeprazole. However, direct comparisons have shown that eradication rates achieved by dual therapy are not as high as those achieved by triple therapy. Indeed, triple therapy with clarithromycin plus omeprazole in combination with amoxicillin or a nitroimidazole has achieved eradication rates of up to 100%. Although 14-day triple drug regimes were initially considered necessary for effective eradication, it now seems clear that 7-day regimes are equally effective. Factors known to influence response to H. pylori eradication therapy include bacterial resistance and patient compliance. A review of 4 studies evaluating the efficacy of dual eradication therapy with clarithromycin plus omeprazole reported an overall incidence of adverse events (patient or investigator reported, whether related to treatment or not) of 45%. The most common adverse event was taste disturbance (an adverse event commonly reported during the development of clarithromycin); nausea, headache, diarrhoea, vomiting and abdominal pain occurred less frequently. Although dual therapy might be expected to cause fewer adverse events than triple therapy this has not been the case in direct comparisons conducted to date. Thus, although clarithromycin plus omeprazole is associated with an H. pylori eradication rate of approximately 70%, 1 week of triple therapy with these 2 drugs together with amoxicillin or a nitroimidazole, which eradicates the organism in approximately 90% of cases, may represent optimal H. pylori eradication therapy.

Anti-Bacterial Agents↗
PubMed1996

Mycophenolate mofetil. A review of its pharmacodynamic and pharmacokinetic properties and clinical efficacy in renal transplantation.

Mycophenolate mofetil is an ester prodrug of the active immunosuppressant mycophenolic acid. It is a noncompetitive, selective and reversible inhibitor of inosine monophosphate dehydrogenase, an important enzyme in the de novo synthesis of guanosine nucleotides in T and B lymphocytes. Mycophenolate mofetil and/or mycophenolic acid inhibit the proliferation of lymphocytes and the production of antibodies induced by a variety of mitogens and antigens. Mycophenolate mofetil is also active in several animal models of transplantation and has produced effects in animals that indicate that it may inhibit the chronic rejection process. Mycophenolate mofetil has been compared with azathioprine or placebo in 3 large, randomised, double-blind, multicentre trials as part of combination immunosuppression therapy with cyclosporin and corticosteroids. Compared with either placebo or azathioprine (1 to 2 mg/kg/day or 100 to 150 mg/day), mycophenolate mofetil 2 or 3 g/day was associated with a significantly lower proportion of patients experiencing acute rejection or treatment failure during the first 6 months after transplantation. Mycophenolate mofetil also tended to be associated with a lower proportion of patients who required a full course of antirejection therapy. However, the proportion of patients who died or who had graft loss was similar between all of the treatment groups. There are currently no data regarding the effects of mycophenolate mofetil on long term patient or graft survival, which are important clinical outcomes in assessing its place in the management of renal transplantation. Clinical trials are also needed to evaluate mycophenolate mofetil in specific patient populations (e.g. repeat renal transplant patients or highly sensitised patients), to determine its efficacy in alternative immunosuppressive protocols and to investigate its use in the transplantation of other solid organs. In summary, mycophenolate mofetil appears to be an attractive new agent in the prevention of graft rejection in renal transplant recipients that has shown superior efficacy to azathioprine. Although long term clinical outcome data are required, mycophenolate is a potentially important advance in transplant immunosuppression.

Animals↗
PubMed1996

Epoetin beta. A review of its pharmacological properties and clinical use in the management of anaemia associated with chronic renal failure.

Epoetin beta is a recombinant form of erythropoietin, the hormone responsible for the maintenance of erythropoiesis. The drug binds to and activates receptors on erythroid progenitor cells which then develop into mature erythrocytes. Epoetin beta increases reticulocyte counts, haemoglobin levels and haematocrit in a dose-proportional manner. These changes are accompanied by beneficial cardiovascular effects, including decreased cardiac output, resting heart rate and left ventricular hypertrophy in patients with chronic renal failure (CRF). Increases of 15 to 54% in haemoglobin levels and 17 to 60% in haematocrit were reported after subcutaneous or intravenous epoetin beta therapy in studies of 8 weeks' to 12 months' duration. Two multicentre clinical trials demonstrated clearly the superior efficacy of epoetin beta over placebo in 229 patients with CRF undergoing haemodialysis. Reduction or elimination of transfusion requirements was reported in studies where this parameter was measured. Comparative data indicate that dosage reductions of approximately 30% compared with intravenous therapy are possible when subcutaneous administration of epoetin beta is used. Haematocrit increased more rapidly in 5 multicentre studies in patients who received epoetin beta subcutaneously than in those who received the same dosage intravenously. Correction of anaemia with epoetin beta is associated with significant improvements in quality of life in patients with CRF. Available data indicate greatest cost-effectiveness in patients who are severely incapacitated by anaemia before treatment. The cost of administration of the drug may also be reduced by the use of the subcutaneous route. Hypertension may occur in patients who receive epoetin beta but may be minimised by avoiding rapid increases in haematocrit (> 0.5%/week), and is managed in most cases with control of fluid status and antihypertensive medication. Although clotting of the vascular access has not been conclusively linked to epoetin beta, caution is recommended in patients undergoing haemodialysis. Increased heparinisation is recommended to prevent clotting in dialysis equipment. Epoetin beta is more effective and/or better tolerated than alternative treatments (e.g. androgenic steroids) for anaemia associated with CRF. It also causes significant improvements in quality of life, exercise capacity and overall well-being. Results of clinical studies indicate that subcutaneous administration is desirable where possible in the majority of patients. Thus, epoetin beta has become established as an effective treatment for anaemia associated with CRF.

Anemia↗