Coral community response to bleaching on a highly disturbed reef.

While many studies of coral bleaching report on broad, regional scale responses, fewer examine variation in susceptibility among coral taxa and changes in community structure, before, during and after bleaching on individual reefs. Here we report in detail on the response to bleaching by a coral community on a highly disturbed reef site south of mainland Singapore before, during and after a major thermal anomaly in 2010. To estimate the capacity for resistance to thermal stress, we report on: a) overall bleaching severity during and after the event, b) differences in bleaching susceptibility among taxa during the event, and c) changes in coral community structure one year before and after bleaching. Approximately two thirds of colonies bleached, however, post-bleaching recovery was quite rapid and, importantly, coral taxa that are usually highly susceptible were relatively unaffected. Although total coral cover declined, there was no significant change in coral taxonomic community structure before and after bleaching. Several factors may have contributed to the overall high resistance of corals at this site including Symbiodinium affiliation, turbidity and heterotrophy. Our results suggest that, despite experiencing chronic anthropogenic disturbances, turbid shallow reef communities may be remarkably resilient to acute thermal stress.

Mixed azide-terminated monolayers: a platform for modifying electrode surfaces.

We have prepared and characterized mixed self-assembled monolayers (SAM) on gold electrodes from azido alkane thiols and various omega-functionalized alkane thiols. In the presence of copper(I) catalysts, these azide-modified surfaces are shown to react rapidly and quantitatively with terminal acetylenes forming 1,2,3-triazoles, via "click" chemistry. The initial azide substituents can be identified and monitored using both grazing-angle infrared (IR) and X-ray photoelectron spectrosopies. Acetylenes possessing redox-active ferrocene substituents react with the azide-terminated mixed SAMs and electrochemical measurements of the ferrocene-modified SAM electrodes have been used to quantify the redox centers attached to these platforms. Time-resolved electrochemical measurements have enabled us to follow the formation of these ferrocene centers and thus to measure the rate of the surface "click" reaction. Under optimal conditions this well-behaved second-order reaction takes place with a rate constant of 1 x 10(3) M(-)(1) s(-)(1). Typical reaction times of several minutes were realized using micromolar concentrations of acetylene. These techniques have been used to construct well-characterized, covalently modified monolayers that can be employed as functional electrode surfaces.

Fleroxacin. A review of its pharmacology and therapeutic efficacy in various infections.

The fluoroquinolone antibacterial agent fleroxacin has a broad spectrum of in vitro activity which encompasses most Gram-negative species (particularly Enterobacteriaceae) and a number of Gram-positive organisms, including methicillin-sensitive staphylococci. It is available as oral and intravenous formulations. In clinical trials, fleroxacin has been evaluated in the treatment of uncomplicated urinary tract infections (single or multiple once-daily oral doses of 200 or 400mg), gonorrhoea and chancroid (single oral doses of 200 or 400mg), complicated urinary tract, nonpneumococcal lower respiratory tract and skin and soft tissue infections and typhoid fever (multiple once-daily oral or intravenous regimens, usually 400 mg/day), bacterial enteritis, and traveller's diarrhoea (single or multiple once-daily oral doses of 400mg). Bacteriological cure rates were generally around 90% or higher in complicated and uncomplicated urinary tract infections, uncomplicated gonorrhoea (approximately 100%), pyelonephritis, bacterial enteritis and typhoid fever, and exceeded 80% in lower respiratory tract, and skin and soft tissue infections and chancroid. These cure rates were similar to, or better than, those achieved with standard comparator antibacterial agents such as penicillins, cephalosporins, cotrimoxazole, or other quinolones. Fleroxacin 400mg once daily also achieved bacteriological cure in approximately 80% of patients with bone and joint infections in preliminary studies. In Japanese studies using a lower dosage of 200 or 300 mg/day, fleroxacin was reported to be bacteriologically effective in a range of infections, including urinary tract and upper and lower respiratory tract infections. Fleroxacin has a relatively long elimination half-life, which allows once-daily administration, and it appears to have less propensity for interactions with other medications in comparison to many other fluoroquinolones. Its tolerability profile is typical of this class of compound, with adverse events mostly relating to the gastrointestinal tract, CNS, and skin and appendages (including phototoxicity). Recent pooled tolerability data from worldwide clinical trials indicate that adverse events are reported by approximately 27% of patients receiving 200 mg/day orally or 400 mg/day orally or intravenously, and 17% of those receiving a single oral dose of 400mg. These exceed incidences reported for established fluoroquinolones, possibly indicating recent trends towards increased rates of reported adverse effects with these agents. However, in direct comparative studies with twice-daily fluoroquinolones, fleroxacin 400mg once daily produced a similar incidence of adverse effects to ofloxacin 800 mg/day and a slightly higher incidence than ciprofloxacin 1000 mg/day, while fleroxacin 200mg once daily produced a similar incidence to norfloxacin 800 mg/day.(ABSTRACT TRUNCATED AT 400 WORDS)

Felodipine. A review of the pharmacology and therapeutic use of the extended release formulation in cardiovascular disorders.

Felodipine is a vascular-selective, dihydropyridine calcium antagonist previously investigated as a conventional tablet formulation administered twice daily. More recently considerable experience has been gained with an extended release (ER) formulation which has the convenience of once daily administration. Felodipine ER has been well studied in patients with essential hypertension. As monotherapy in mild to moderate essential hypertension, felodipine ER is at least as effective in reducing blood pressure as other calcium antagonists, beta-blockers, diuretics and ACE inhibitors, with some results favouring felodipine ER at a statistically significant level at the dosages used. It is also effective combined with controlled release metoprolol or enalapril in patients with mild to moderate essential hypertension. In patients with more severe forms of essential hypertension uncontrolled by beta-blocker and/or diuretic therapy, felodipine ER was effective as an 'add-on' therapy in placebo-controlled trials, and, at the dosages used, more effective than either sustained release nifedipine or nitrendipine. Felodipine produces effective control of blood pressure without negative effects on cardiac performance. In addition to its antihypertensive action, results suggest that felodipine therapy is associated with significant regression of left ventricular hypertrophy. Furthermore, it appears suitable for use in patients with concomitant diabetes, renal dysfunction or asthma, and is also being investigated for use in patients with congestive heart failure or angina pectoris. Felodipine ER is an effective drug for the treatment of all grades of essential hypertension, and can be used both as monotherapy and in combination with other antihypertensive agents. Further clinical experience should fully establish the long term tolerability of felodipine ER and consequently its place in therapy relative to other accepted antihypertensive drugs. However, with the convenience of once daily administration, felodipine ER is a worthwhile innovation in the treatment of hypertension.

Enalapril. A reappraisal of its pharmacology and therapeutic use in hypertension.

Enalapril, an angiotensin converting enzyme (ACE) inhibitor usually administered orally once daily, decreases blood pressure by lowering peripheral vascular resistance without increasing heart rate or output. It is effective in lowering blood pressure in all grades of essential and renovascular hypertension. Patients not responding adequately to enalapril monotherapy usually respond with the addition of a thiazide diuretic (or a calcium antagonist or beta-blocker), and rarely require a third antihypertensive agent. Enalapril is at least as effective as other established and newer ACE inhibitors, and members of other antihypertensive drug classes including diuretics, beta-blockers, calcium antagonists and alpha-blockers, but therapy with enalapril may be less frequently limited by serious adverse effects or treatment contraindications than with other drug classes. The most frequent adverse effect limiting all ACE inhibitor therapy in clinical practice is cough. This favourable profile of efficacy and tolerability, and the substantial weight of clinical experience, explain the increasing acceptance of enalapril as a major antihypertensive treatment and supports its use as logical first-line therapeutic option.

Interferon gamma-1b. A review of its pharmacology and therapeutic potential in chronic granulomatous disease.

Chronic granulomatous disease is a group of rare x-linked or autosomal genetic disorders of the phagocytic NADPH oxidase system involved in host defence against various microorganisms. It is manifested by a common phenotype consisting of recurrent serious, life-threatening infection and granuloma formation. Following the finding that interferon gamma-1b (IFN gamma-1b) can potentiate phagocyte activity in some other disease states as well as restoring defective phagocyte NADPH oxidase system activity in at least some patients with chronic granulomatous disease, a large-scale placebo-controlled trial was undertaken with IFN gamma-1b in patients with chronic granulomatous disease. Long term treatment with a therapeutic dosage of IFN gamma-1b produced a significant reduction in the incidence of serious clinical events necessitating hospitalisation. The relative risk of serious infection and the number of days in hospital were each reduced by about two-thirds, and the mean duration of hospital stay by about one-third in those who did experience infection. The greatest therapeutic benefit was found in patients aged less than 10 years, but all patients were improved regardless of age, sex, use of prophylactic antibiotics or genetic pattern of inheritance. The drug was well tolerated with the commonest adverse effects (e.g. fever, headache, chills, injection site erythema) usually being mild, transient, and relieved by symptomatic treatment. IFN gamma-1b therefore provides an effective and well tolerated therapy for patients with chronic granulomatous disease, offering an important clinical advance in the treatment of this rare genetic disorder by improving the prognosis of its serious and life-threatening infectious sequelae.

Ofloxacin. A reappraisal of its antimicrobial activity, pharmacology and therapeutic use.

Ofloxacin is a fluoroquinolone whose primary mechanism of action is inhibition of bacterial DNA gyrase. In vitro it has a broad spectrum of activity against aerobic Gram-negative and Gram-positive bacteria, although it is poorly active against anaerobes. Ofloxacin, unlike most other broad spectrum antibacterial drugs, can be administered orally as well as intravenously. Penetration into body tissues and fluids is highly efficient. Clinical trials with orally and intravenously administered ofloxacin have confirmed its potential for use in a wide range of infections, where it has generally proved as effective as standard treatments. Ofloxacin in well tolerated, and in comparison with other available fluoroquinolones is less likely to cause clinically relevant drug interactions. Ofloxacin thus offers a valuable oral treatment (with an option for intravenous administration if necessary) for use in a wide range of clinical infections, but with a particular advantage in more severe or chronic infections when recourse to parenteral broad spectrum agents would normally be required, thereby providing cost savings and additionally allowing outpatient treatment.

Gallium nitrate. A review of its pharmacological properties and therapeutic potential in cancer related hypercalcaemia.

Gallium nitrate, a novel drug for the treatment of cancer-related hypercalcaemia, inhibits osteoclast activity but does not affect osteoclast morphology or viability. Limited clinical experience in patients with cancer-related hypercalcaemia indicates that gallium nitrate is effective in restoring normocalcaemia in 75 to 85% of patients and is well tolerated in those with preserved renal function, producing few clinically relevant adverse effects. In comparative clinical trials it proved a more effective antihypercalcaemic agent than calcitonin or etidronate and produced a longer lasting normocalcaemic response. Gallium nitrate would appear to be indicated in symptomatic patients with cancer-related hypercalcaemia who have failed to respond to adequate rehydration.

Perindopril. A review of its pharmacological properties and therapeutic use in cardiovascular disorders.

Perindopril is a long acting angiotensin converting enzyme (ACE) inhibitor, which displays similar pharmacodynamic properties to other agents in this class. In common with enalapril, it is also a prodrug. After absorption, perindopril is hydrolysed to the active metabolite, perindoprilat, and with once daily administration adequate 24-hour inhibition of ACE is obtained. Perindopril 4 to 8mg once daily is usually effective for blood pressure control in patients with mild to moderate essential hypertension. Those patients who do not respond adequately to monotherapy with perindopril usually respond with the addition of a second agent, such as a thiazide diuretic. General practice trials indicate that perindopril is at least as effective and as well tolerated as usual therapeutic dosages of captopril, atenolol or hydrochlorothiazide plus amiloride in mild to moderate essential hypertension. Preliminary results indicate that perindopril may also be effective in patients with severe hypertension or congestive heart failure. Perindopril is generally well tolerated and has an adverse effect profile similar to that of other ACE inhibitors. It further clinical experience confirms initial findings, perindopril is likely to represent a useful alternative to other members of the ACE inhibitor class in all grades of hypertension and congestive heart failure.

Tenoxicam. An update of its pharmacology and therapeutic efficacy in rheumatic diseases.

Tenoxicam administered orally, rectally or parenterally is an effective analgesic and anti-inflammatory agent for the symptomatic treatment of rheumatoid arthritis, osteoarthritis, ankylosing spondylitis and various rheumatic conditions such as tendinitis, bursitis, sciatica, back pain and gouty arthritis. In clinical trials its efficacy is at least equivalent to that of other NSAIDs and it is at least as well tolerated as piroxicam and probably better tolerated than diclofenac, indomethacin and ketoprofen. Compared with many other NSAIDs, tenoxicam offers certain advantages in that it is conveniently administered once daily and dosage adjustment is not required in the elderly or in patients with renal or hepatic impairment.

Transdermal nitroglycerin (glyceryl trinitrate). A review of its pharmacology and therapeutic use.

Nitroglycerin (glyceryl trinitrate) has been used for many years via the sublingual route for treating acute anginal attacks. In recent years transdermal delivery of nitroglycerin has gained popularity for prophylaxis against angina. However, nitrate tolerance appears to be a therapeutic problem with all long-acting nitrates regardless of delivery mechanism, and it occurs in most patients with stable angina treated with continuous 24-hour application of nitroglycerin patches. Since continuous 24-hour plasma concentrations of nitroglycerin do not appear to be desirable, alternative approaches to therapy are needed. A simple method to minimise tolerance with transdermal nitroglycerin patches is to remove the patch at bedtime and reapply a new patch in the morning. Such intermittent therapy allows a patch-free period during the night, when most patients experience few angina attacks, but optimises nitrate sensitivity during the daytime. However, the place of intermittent nitroglycerin patch therapy in the treatment of stable angina needs clarification with further study, particularly comparisons with other long-acting forms of nitrates. There are insufficient data to recommend the use of transdermal nitroglycerin patches in the treatment of patients with unstable angina or congestive heart failure. In conclusion, transdermal nitroglycerin patches offer a convenient and cosmetically acceptable dosage form which has potential use in stable angina if administered as an intermittent regimen providing a patch-free period each night.

Simvastatin. A review of its pharmacological properties and therapeutic potential in hypercholesterolaemia.

Simvastatin (epistatin; synvinolin; MK 733), an HMG-CoA reductase inhibitor, acts by decreasing cholesterol synthesis and by increasing low density lipoprotein (LDL) catabolism via increased LDL receptor activity. In patients with heterozygous familial and nonfamilial hypercholesterolaemia, orally administered simvastatin 10 to 40mg once daily reduces plasma total and LDL-cholesterol concentrations by about 30 to 45%. It also produces a beneficial moderate decrease in plasma triglycerides and a small, although significant, increase in high density lipoprotein (HDL)-cholesterol. Like many other hypocholesterolaemic agents simvastatin does not appear useful in patients with homozygous familial hypercholesterolaemia who lack LDL receptors. The hypocholesterolaemic activity of simvastatin is greater than that of the bile acid sequestrants, probucol and the fibrates. Combined administration of simvastatin with bile acid sequestrants results in further reductions in plasma cholesterol levels beyond those seen with either drug alone. Simvastatin appears well tolerated in the short to medium term, but its long term tolerability needs to be confirmed. No comparisons of simvastatin and other HMG-CoA reductase inhibitors have been reported. As yet there have been few investigations to determine the impact of simvastatin or other HMG-CoA reductase inhibitors on cardiovascular events relative to their hypocholesterolaemic effects, but at least one such trial is ongoing. Simvastatin, like other HMG-CoA reductase inhibitors, has considerable potential advantages over other classes of hypocholesterolaemic agents, i.e. the magnitude of its cholesterol-lowering effect and convenience of administration. If further study confirms long term tolerability and an impact on cardiac mortality and morbidity, then simvastatin and others of its class should offer a significant new approach to the treatment of hypercholesterolaemia.

Cefotaxime. An update of its pharmacology and therapeutic use.

Cefotaxime was the first 'third generation' cephalosporin to be marketed and is administered intramuscularly or intravenously. Similar to other agents of this class, it has a broad spectrum of in vitro activity, particularly against Enterobacteriaceae, including beta-lactamase-producing strains. Cefotaxime forms a metabolite, desacetylcefotaxime, which is antibacterially effective against many bacteria per se and acts additively or synergistically with cefotaxime against many strains. Since the first review of cefotaxime in the Journal, further studies have confirmed its value in the treatment of various infections: complicated urinary tract infections, lower respiratory tract infections, bacteraemia, meningitis, uncomplicated gonorrhoea, infections of skin and soft tissue and of bone and joints, and obstetric and gynaecological infections. Cefotaxime is effective as an empirical treatment of suspected infection due to susceptible organisms in immunocompromised patients and is of proven efficacy in serious, life-threatening infections in general. Cefotaxime reduces the incidence of postsurgical infection but the role of third generation cephalosporins in prophylaxis remains to be determined. The indications for which cefotaxime and other 'third generation' cephalosporins would be considered the most appropriate therapy remain largely dependent upon such factors as varied as cost, local medical custom, decisions of regulatory agencies and geographical patterns of bacterial resistance. Cefotaxime nevertheless represents a valuable 'third generation' cephalosporin of great clinical value in certain infectious conditions, in particular those which are serious and life-threatening and where resistance to therapies is creating a clinical problem.

Naproxen. A reappraisal of its pharmacology, and therapeutic use in rheumatic diseases and pain states.

Naproxen is a nonsteroidal anti-inflammatory drug (NSAID) advocated for use in painful and inflammatory rheumatic and certain nonrheumatic conditions. It may be administered orally or rectally using a convenient once or twice daily regimen. Dosage adjustments are not usually required in the elderly or those with mild renal or hepatic impairment although it is probably prudent to start treatment at a low dosage and titrate upwards in such groups of patients. Numerous clinical trials have confirmed that the analgesic and anti-inflammatory efficacy of naproxen is equivalent to that of the many newer and established NSAIDs with which it has been compared. The drug is effective in many rheumatic diseases such as rheumatoid arthritis, osteoarthritis, ankylosing spondylitis and nonarticular rheumatism, in acute traumatic injury, and in the treatment of and prophylaxis against acute pain such as migraine, tension headache, postoperative pain, postpartum pain and pain associated with a variety of gynaecological procedures. Naproxen is also effective in treating the pain and associated symptoms of primary or secondary dysmenorrhoea, and decreases excessive blood loss in patients with menorrhagia. The adverse effect profile of naproxen is well established, particularly compared with that of many newer NSAIDs, and the drug is well tolerated. Thus, the efficacy and tolerability of naproxen have been clearly established over many years of clinical use, and it can therefore be considered as a first-line treatment for rheumatic diseases and various pain states.

Guar gum. A review of its pharmacological properties, and use as a dietary adjunct in hypercholesterolaemia.

Guar gum is a dietary fibre advocated for use in lowering serum total cholesterol levels in patients with hypercholesterolaemia. Its mechanism of action is proposed to be similar to that of the bile-sequestering resins. Although guar gum is also employed as an adjunct in non-insulin-dependent diabetic patients this review is restricted to its efficacy as a hypolipidaemic agent. Clinical trials indicate that, when used alone, guar gum may reduce serum total cholesterol by 10 to 15%, although some studies show no significant response. An attenuation of this effect during longer term treatment has been seen but evidence of this effect is equivocal. As an adjunct to established therapies (bezafibrate, lovastatin or gemfibrozil) guar gum has shown some promise: it may produce a further reduction in total cholesterol of about 10% in patients not responding adequately to these drugs alone. Gastrointestinal effects, notably flatulence, occur relatively frequently and may be considered unacceptable by some patients. Standardization of formulations and methods of administration of guar gum is required to clarify its pharmacological and clinical properties. Thus, on the basis of presently available evidence guar gum as monotherapy may be considered at most modestly effective in reducing serum cholesterol levels. Nonetheless, further investigation of guar gum is warranted, particularly its use as an adjunct to produce additional reductions in serum cholesterol in patients not responding optimally to other lipid-lowering agents.

Amoxicillin/clavulanic acid. An update of its antibacterial activity, pharmacokinetic properties and therapeutic use.

Clavulanic acid enhances the antibacterial spectrum of amoxicillin by rendering most beta-lactamase-producing isolates susceptible to the drug. In clinical trials amoxicillin/clavulanic acid is clinically and bacteriologically superior to amoxicillin alone and at least as effective as numerous other comparative agents, such as orally administered cephalosporins, cotrimoxazole, doxycycline and bacampicillin, in the treatment of adults and children with the most common forms of infection encountered in general practice, i.e. urinary tract infections, upper and lower respiratory tract infections, otorhinolaryngological infections, and skin and soft tissue infections. It may also provide effective treatment for uncomplicated gonorrhoea, chancroid and gynaecological infections as well as acting as a prophylactic agent against surgical infection. Thus, in general practice environments where beta-lactamase production has restricted the effectiveness of amoxicillin, the combination of clavulanic acid with amoxicillin has clearly extended the usefulness of a tried and proven first-line antibacterial agent.

Ramipril. A review of its pharmacological properties and therapeutic efficacy in cardiovascular disorders.

Ramipril is a long acting angiotensin converting enzyme (ACE) inhibitor, which exhibits similar pharmacodynamic properties to captopril and enalapril. Like enalapril it is a prodrug, which is hydrolysed after absorption to form the active metabolite ramiprilat which has a long elimination half-life, permitting once daily administration. In hypertensive patients daily doses in the range 2.5 to 20 mg are usually effective in reducing high blood pressure and maintaining satisfactory control during long term treatment. Patients who do not respond adequately to monotherapy with ramipril usually respond with the addition of a diuretic such as hydrochlorothiazide or piretanide. Ramipril 5 to 10 mg once daily shows comparable antihypertensive efficacy to usual therapeutic dosages of captopril, enalapril and atenolol in patients with mild to moderate essential hypertension. Preliminary data indicate that ramipril may be effective in indications such as severe essential hypertension and renal hypertension. It has also displayed beneficial effects in patients with moderate to severe congestive heart failure. Ramipril has been well tolerated and exhibits an adverse effect profile typical of ACE inhibitors as a class. In conclusion, ramipril will likely represent a useful alternative ACE inhibitor for use in patients with hypertension or congestive heart failure.

Flunarizine. A reappraisal of its pharmacological properties and therapeutic use in neurological disorders.

Flunarizine is a class IV calcium antagonist with a pharmacological profile which suggests its therapeutic potential in a number of neurological and cerebrovascular disorders. It is an effective prophylactic treatment for common or classic migraine in children and adults, and it appears at least as effective as a number of other agents which act by different pharmacological mechanisms, including pizotifen (pizotyline), cinnarizine, methysergide, nimodipine, metoprolol, propranolol, aspirin and cyclandelate. Flunarizine is also effective in reducing the frequency of seizures, when used as an 'add-on' treatment, in some patients with partial or generalised epilepsy resistant to maximal therapy with a combination of several conventional antiepileptic drugs. Placebo-controlled studies show that flunarizine is effective in the treatment of vertigo and associated symptoms of either peripheral or central origin, and in the treatment of cerebrovascular insufficiency where psychological symptoms, rather than vertigo, are the primary symptoms. In the treatment of vertigo, flunarizine appears at least as effective as cinnarizine and more effective than nicergoline, betahistine dichlorhydrate, pentoxifylline (oxpentifylline) and vincamine. Flunarizine therefore is useful in the prophylaxis of migraine, an effective treatment for vertigo and a worthwhile alternative as 'add-on' therapy in patients with epilepsy resistant to conventional drugs.

Tissue-type plasminogen activator. A review of its pharmacology and therapeutic use as a thrombolytic agent.

Coronary arterial thrombolysis is becoming an established treatment of acute myocardial infarction. If given early enough, it recanalises occluded coronary arteries, salvages myocardial function and reduces mortality. A reduction of mortality in patients with acute myocardial infarction has now been demonstrated for streptokinase, anisoylated plasminogen streptokinase activator complex (APSAC; anistreplase) and recombinant tissue-type plasminogen activator (rt-PA). From the biochemical point of view, rt-PA has several attractive properties. It is similar to or identical with the physiological plasminogen activator in blood, it does not induce an antibody response, and it is more fibrin-specific than most or all other currently known thrombolytic agents. The rate of recanalisation of occluded coronary arteries with rt-PA is about 60 to 80% in non-comparative and placebo-controlled trials. rt-PA was similar in efficacy to urokinase in the only trial to compare the 2 agents. In 2 comparative trials evaluated by meta-analysis, rt-PA appeared more effective than streptokinase for the early recanalisation of occluded arteries. Both agents were comparable in their effects on left ventricular function in 2 comparative trials, but further study is needed to conclusively evaluate this parameter. Moreover, both agents reduce inhospital mortality, but much larger direct comparative trials are required before scientifically valid statements can be made on the relative clinical efficacy of available thrombolytic agents in terms of their effects on both morbidity and mortality. Thus, rt-PA constitutes a notable contribution of recombinant DNA technology to the treatment of thromboembolic disease, the main cause of death and disability in Western societies.

Muromonab CD3. A review of its pharmacology and therapeutic potential.

Muromonab CD3 (Orthoclone OKT3, Orthoclone, OKT3) is the first monoclonal antibody to become available for therapy in humans. In effect it blocks all cytotoxic T cell function. Clinical trials show that muromonab CD3 is effective in reversing acute renal, hepatic, cardiac and combined kidney-pancreas transplant rejection episodes. It has also been shown to be effective in the treatment of rejections resistant to conventional treatment. As such it offers a significant alternative when no other therapeutic option remains open. Other clinical trials have shown that muromonab CD3 is more effective than high-dose corticosteroids in reversing first episodes of acute renal and hepatic rejection. Additionally, it appears effective as a prophylactic treatment against acute renal and cardiac rejection in the immediate post-transplantation period. Preliminary studies also indicate that it may be effective in preventing or reversing graft-versus-host disease in bone marrow transplant patients. The development of neutralising antibodies may limit the effectiveness of a second course of muromonab CD3 therapy in some patients. In conclusion, muromonab CD3 offers a significant new approach to immunosuppressive therapy and has provided a valuable therapeutic alternative for the treatment of acute solid organ transplant rejection.