Carprofen: a new nonsteroidal antiinflammatory drug. Pharmacology, clinical efficacy and adverse effects

Because a patient with arthritis (especially rheumatoid arthritis) may respond to one NSAID but not another, any addition to the ranks of these agents may be of clinical benefit to at least some of the millions of patients afflicted with rheumatoid arthritis, osteoarthritis and related conditions. In terms of potency both as an antiinflammatory and as an analgesic, carprofen appears to be in the middle of the NSAID range--roughly one-fourth as potent as indomethacin, and five times as potent as ibuprofen, milligram for milligram. The two most obvious potential advantages of carprofen are that it seems to have a low profile of major gastrointestinal adverse reactions (it may cause minor complaints similar to those seen with indomethacin, but thus far has caused no documented gastric or duodenal ulcers at 300 mg/d); and that, like naproxen, it offers the convenience of twice-a-day dosing. In clinical experience thus far, the two most bothersome adverse effects seen with carprofen have been a rare but serious photosensitivity reaction and minor, temporary elevations of liver function tests in approximately 14-20% of patients treated (although as yet there have been no reported cases of jaundice or hepatitis). For some patients with rheumatoid arthritis, osteoarthritis or related conditions, particularly for those who cannot tolerate aspirin or indomethacin or who want or need the convenience of twice-a-day dosing, carprofen may represent a useful therapeutic option to the NSAIDs previously available in this country.     

Pharmacology, efficacy, and adverse effects of halazepam, a new benzodiazepine

Halazepam is a new benzodiazepine derivative that is molecularly similar to chlordiazepoxide and diazepam. Animal studies indicated that halazepam produces sedative and antianxiety effects with less toxicity than chlordiazepoxide or diazepam. Computer EEG and somatosensory evoked potential studies demonstrated that halazepam has a significant effect on the EEG, characteristic of changes that occur with benzodiazepines. In initial clinical studies, halazepam exhibited not only anxiolytic properties but also reduced symptoms of depression and had a therapeutic effect on epilepsy. In preliminary, uncontrolled clinical trials, halazepam was effective in ameliorating anxiety and tension in alcoholic and acute schizophrenic patients, with few adverse effects. Later double-blind studies generally demonstrated that halazepam is significantly superior to placebo in alleviating symptoms of anxiety and tension. Most comparative studies indicate that halazepam is equal to or more effective than diazepam with a lower frequency of side effects. Halazepam does not increase hostility and aggression, as chlordiazepoxide and diazepam have been shown to do, and it is effective in both situational and characterologic anxiety. Drowsiness and slight dry mouth are the only side effects reported in more than isolated instances, although geriatric patients may frequently become ataxic with higher doses.     

Pharmacology, clinical efficacy and adverse effects of vindesine sulfate, a new vinca alkaloid

Vindesine is a new vinca alkaloid antineoplastic agent derived from vinblastine. However, its antineoplastic spectrum more closely resembles that of vincristine. Clinical studies indicate activity against acute leukemia, lung cancer, carcinoma of the breast, squamous cell carcinoma of the esophagus and head and neck, Hodgkin's disease and non-Hodgkin's lymphomas. Pharmacokinetic studies indicate that vindesine exhibits a triphasic elimination pattern with a terminal half-life of 24.2 hours. Elimination is primarily through hepatic metabolism. The major side effects associated with vindesine therapy are myelosuppression and neurotoxicity. Other side effects include alopecia, nausea and vomiting and local tissue irritation associated with extravasation. Vindesine will be a positive addition to the antineoplastic armamentarium. The full extent of its activity remains to be established.     

Pharmacology, clinical efficacy, and adverse effects of piroxicam, a new nonsteroidal anti-inflammatory agent

Piroxicam, a new non-steroidal anti-inflammatory drug, possesses analgesic, antipyretic, and anti-inflammatory properties and inhibits platelet aggregation in animal models. Its elimination half-life is 38 hours, and hepatic metabolism to inactive metabolites is the primary route of elimination. Less than 10% of a dose appears unchanged in the urine. Clinical studies demonstrate that piroxicam's analgesic and anti-inflammatory properties are useful in the management of rheumatoid arthritis and osteoarthritis. Limited clinical studies suggest that piroxicam may be useful in the management of acute gouty arthritis, ankylosing spondylitis, acute musculoskeletal disorders, and as an analgesic. The gastrointestinal system is the major site of adverse effects. Piroxicam is currently marketed in 20 mg capsules and once daily dosing has proven effective for many patients.     

Piretanide. A preliminary review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy

Piretanide is a potent 'loop' diuretic whose principal site of action is in the thick ascending limb of the loop of Henle. When administered orally or intravenously to healthy volunteers it rapidly increases diuresis and electrolyte excretion, and the effects are short-lived. In comparative studies, piretanide has generally been found to be 5 to 7 times more potent than frusemide (furosemide) but only one-tenth as potent as bumetanide, on a weight-for-weight basis. Piretanide 6 to 12 mg/day, in conventional or sustained release formulations, has been shown to significantly lower elevated blood pressure in a large proportion of patients with mild to moderate hypertension. Comparative trials of up to 3 months duration indicate that at this dosage piretanide is of comparable antihypertensive efficacy as hydrochlorothiazide 50 to 100 mg/day, but has significantly less effect on serum potassium levels. Short term studies in patients with oedema caused by renal, hepatic or cardiac failure demonstrated that piretanide 6 to 9 mg is of similar diuretic potency as frusemide 40 mg and bumetanide 1 mg. In medium term trials in patients with congestive heart failure piretanide 6 mg/day produced equivalent symptomatic improvement as frusemide 40 mg/day. When used to treat oedema caused by liver disease, piretanide 12 to 24 mg/day was successful in only about 50% of patients, but spironolactone added to the treatment regimen greatly increased the response rate. Generally, piretanide has been well-tolerated in clinical trials, although the conventional tablet formulation has caused a relatively high incidence of acute adverse effects--these were greatly reduced with the introduction of the sustained release formulation. Serum concentrations of most electrolytes have not shown any consistent adverse trends and hyperuricaemia and hypokalaemia have been encountered infrequently. Thus, piretanide appears to offer an effective alternative to other 'loop' diuretics for the treatment of oedematous diseases and to hydrochlorothiazide for the management of mild to moderate hypertension. However, its relative place in therapy remains to be clarified with wider clinical experience.     

Fenoterol: a beta2-adrenergic agonist for use in asthma. Pharmacology, pharmacokinetics, clinical efficacy and adverse effects

Fenoterol (hydroxyphenylorciprenaline) is chemically closely related to metaproterenol (orciprenaline). It has a higher bronchodilating potency than metaproterenol, albuterol (salbutamol in Europe) or terbutaline. The beta 2 selectivity of fenoterol at normal oral and inhaled doses is the same as for albuterol and terbutaline. Its pharmacodynamic effects are similar to those of other selective beta 2-adrenoceptor agonists. It has a high first-pass metabolism. The long half-life previously reported in the literature (7 hours) is mainly the half-life of inactive fenoterol metabolites. The duration of action at equipotent bronchodilating doses seems to be the same as for albuterol and terbutaline, and not longer, as previously reported. Inhalation of beta-adrenoceptor agonists is the superior route of administration. Side effects do not usually occur at normal therapeutic doses. One puff of fenoterol (200 micrograms) is about equipotent to 2 puffs of albuterol (2 X 100 micrograms) or 2 puffs of terbutaline (2 X 250 micrograms) with the same duration of effect. In patients who overdose with the metered-dose inhaler (MDI), side effects occur at half the number of puffs with fenoterol. Dosage for an acute attack in children is 1 puff (200 micrograms), repeated within 5 minutes if necessary; in adults 1-3 puffs can be given. For maintenance therapy, the dose in adults is 1-2 puffs 2-4 times daily, while in children 1 puff at night and 1 in the morning may be sufficient. The usual oral dosage has been 5-10 mg 3 times daily.     

Piretanide,a potassium stable diuretic,in the treatment of essential hypertension

Summary In a randomized, double blind, parallel group study in out patients with mild to moderate essential hypertension the effects of piretanide on serum electrolytes and on blood pressure were compared with those of triamterene alone and the combination piretanide + triamterene. 136 patients entered the study; 18 patients did not fulfill the inclusion criteria (RR_diast was below 95 mmHg or above 120 mmHg) at the end of the placebo period, 6 dropped out due to side effects, and 1 due to lack of efficacy. Data from 1 patient were not evaluated because the patient did not come regularly for checkups. The results for 110 patients were analyzed. Piretanide 6 mg b.d. and piretanide 6 mg + triamterene 50 mg b.d. produced a significant reduction both in supine and erect blood pressure, which was evident at 2 weeks and which increased over the ensuing 12 week trial period. A mean maximal fall of 16.5% was noted in the piretanide group and 15% in the piretanide + triamterene group. Triamterene alone (50 mg b.d.) also reduced diastolic and systolic blood pressures but the reduction was significantly less (diastolic blood pressure) than in both the piretanide groups, and it showed a more rapid return to pretreatment level during a placebo washout phase at the end of the study. A reduction in standing diastolic blood pressure below 95 mmHg was attained in 84% of patients in the piretanide group, 82% in the piretanide + triamterene group and in only 58% of the triamterene group. There were no significant changes within groups nor differences between the three groups in serum potassium or magnesium. 7 patients were withdrawn from the study because of side-effects due to too marked a clinical action (polyuria, orthostatic disorders and hypotension), one from the piretanide group, and the others in the piretanide + triamterene group. One patient in the triamterene group left the study prematurely due to the lack of effect.     

Pharmacology, toxicology, clinical efficacy, and adverse effects of calcium polycarbophil, an enteral hydrosorptive agent

Calcium polycarbophil is the calcium salt of polyacrylic acid crosslinked with divinyl glycol. It is chemically and physiologically inert. In dilute alkali it possesses marked hydrophilic capacity (60 to 100 times its weight), which is the basis for its therapeutic use. In daily dosages of 4 to 5 g in adults, it appears to be quite safe, is non-toxic, does not interfere with digestion or absorption, and does not cause gastrointestinal irritation. It appears to be effective in the treatment of both constipation and diarrhea due to functional or organic causes. Several days of continuous use are necessary before effectiveness becomes apparent. Clinical studies, of which there are relatively few, range from uncontrolled, unblinded evaluations of an almost anecdotal nature to well controlled, double-blind, crossover studies. Additional carefully controlled studies on dietary influences, exercise, and patient compliance would be helpful. Adverse effects, which are minimal, include epigastric fullness or heaviness, abdominal distention and bloating, and flatulence. As with all bulk-forming agents, calcium polycarbophil should not be used by persons who have stenotic lesions of the gastrointestinal tract.     

影响西罗莫司药动学、疗效及不良反应的因素分析

目的:分析各影响西罗莫司的体内药动学参数、临床疗效及不良反应的因素,为临床个体化用药提供参考。方法:通过国内外文献分析,归纳个体差异、患者状态、共服药物及用药方案等因素对西罗莫司药动学参数、临床疗效及不良反应的影响。结果:西罗莫司的治疗窗窄、个体差异化大,可致高脂血症、贫血、白细胞及血小板减少等不良反应。结论:多种因素共同影响西罗莫司的临床应用,需综合考虑以实现个体化用药及确保用药安全。     

Serotonin releasing agents. Neurochemical, therapeutic and adverse effects

This review summarizes the neurochemical, therapeutic and adverse effects of serotonin (5-HT) releasing agents. The 5-HT releaser (plus minus)-fenfluramine is composed of two stereoisomers, (+)-fenfluramine and (minus sign)-fenfluramine, which are N-de-ethylated to yield the metabolites, (+)-norfenfluramine and (minus sign)-norfenfluramine. Fenfluramines and norfenfluramines are 5-HT transporter substrates and potent 5-HT releasers. Other 5-HT releasing agents include m-chlorophenylpiperazine (mCPP), a major metabolite of the antidepressant drug trazodone. Findings from in vitro and in vivo studies support the hypothesis that fenfluramines and mCPP release neuronal 5-HT via a non-exocytotic carrier-mediated exchange mechanism involving 5-HT transporters. (+)-Norfenfluramine is a potent 5-HT(2B) and 5-HT(2C) receptor agonist. The former activity may increase the risk of developing valvular heart disease (VHD), whereas the latter activity is implicated in the anorectic effect of systemic fenfluramine. Anorectic agents that increase the risk of developing primary pulmonary hypertension (PPH) share the common property of being 5-HT transporter substrates. However, these drugs vary considerably in their propensity to increase the risk of PPH. In this regard, neither trazodone nor mCPP is associated with PPH. Similarly, although some 5-HT substrates can deplete brain 5-HT (fenfluramine), others do not (mCPP). In addition to the established indication of obesity, 5-HT releasers may be helpful in treating psychiatric problems such as drug and alcohol dependence, depression and premenstrual syndrome. Viewed collectively, it seems possible to develop new medications that selectively release 5-HT without the adverse effects of PPH, VHD or neurotoxicity. Such agents may have utility in treating a variety of psychiatric disorders.     

Cefonicid: a long-acting, second-generation cephalosporin. Antimicrobial activity, pharmacokinetics, clinical efficacy and adverse effects

Cefonicid is a new second-generation cephalosporin with a broad antimicrobial spectrum of activity and a prolonged serum elimination half-life. It has good in vitro activity against methicillin-sensitive Staphylococcus aureus, nonenterococcal streptococci, Hemophilus influenzae, Neisseria gonorrhoeae, Neisseria meningitidis and many of the commonly isolated Enterobacteriaceae. Organisms usually resistant to cefonicid include species of Pseudomonas, Serratia, Acinetobacter and Providencia, and Bacteroides fragilis. The drug is 98% protein bound in human serum, which probably contributes to its significant reduction of antimicrobial activity measured in serum. Limited clinical trials have demonstrated it to be effective for surgical prophylaxis and for treating infections of the urinary tract, lower respiratory tract and bone. Failures have been reported in treatment of soft tissue infections and endocarditis caused by S. aureus. A potential cost reduction may be achieved by administering a single daily dose of cefonicid for established infections or a single preoperative dose for effective surgical prophylaxis instead of multiple-dose regimens of other, similar agents.     

Pharmacology of Bay g 2821, a long-acting,high-ceiling diuretic

Summary

Bay g 2821 is a diuretic, from a new class of chemical substances, with both the efficacy of diuretics with a high-ceiling activity, such asfurosemide, bumetanide and ethacrynic acid, and the prolonged duration of action of thiazides. Pharmacological investigations showed that Bay g 2821 was more potent than fur osemide in dogs but less potent in rats. Bay g 2821 did not differ from furosemide in excretion of electrolytes. Further studies showed that Bay g 2821 had an antihypertensive effect in dogs, spontaneously hypertensive rats, and in rats with artificially-induced renal hypertension. Other pharmacological studies did not reveal any other significant effects.     

Beclomethasone dipropionate inhaler: a review of its pharmacology, therapeutic value and adverse effects. I: Asthma.

Beclomethasone dipropionate is a topically active corticosteroid used as an adjuvant in the control of chronic asthma when given by inhalation as an aerosol. It is not intended for treatment of acute attacks. It appears that the main difference between beclomethasone dipropionate and other corticosteroids previously used by inhalation is its high topical activity together with a lower systemic activity due to metabolic inactivation of the swallowed portion of the dose. Clinical experience has shown that at doses of 200 to 600mug daily, beclomethasone dipropionate inhaler is preferable to oral corticosteroids, because of lack of side-effects, when adult patients and children who are inadequately controlled by full doses of sodium cromoglycate and bronchodilators, are first considered to need maintenance corticosteroids. Inhaled beclomethasone dipropionate can allow a worthwhile reduction in maintenance doses of systemic corticosteroids in many patients already receiving these drugs and can replace systemic steroids entirely in some patients, particularly when their initial dose of steroids is less than 10mg daily of prednisone or its equivalent. Substitution should be attempted when the patient's asthma is well controlled on their usual doses of systemic steroids and full doses of other adjuvant therapy. Withdrawal of systemic corticosteroids should be performed slowly and carefully. Because recovery from impaired adrenocortical function caused by prolonged systemic steroid therapy is usually slow, special care is necessary for 9 to 12 months after transfer to beclomethasone dipropionate aerosol until the hypothalamo-pituitary-adrenal axis has sufficiently recovered to cope with emergencies such as trauma, surgery, severe infections or an acute attack of asthma. It is essential that additional therapy including high doses of systemic corticosteroids be used immediately to control any acute exacerbation of asthma which occurs during maintenance therapy with beclomethasone dipropionate aerosol. Tests of adrenal function suggest that beclomethasone dipropionate at dosages of 400 to 800 mug daily has little or no adverse effect. The most common side-effect associated with the continuous use of beclomethasone dipropionate inhaler has been oropharyngeal candidiasis, which appears to be dose-related and more common in women than in men. Systemic steroid withdrawal effects, like being generally unwell, and exacerbation of underlying allergic diseases such as allergic rhinitis, have been reported after substitution of beclomethasone dipropionate inhaler for systemic steroids. However, systemic withdrawal effects seldom occur if systemic steroids are withdrawn slowly.     

Bitolterol mesylate: a beta-adrenergic agent. Chemistry, pharmacokinetics, pharmacodynamics, adverse effects and clinical efficacy in asthma

Bitolterol, (3-4 diester colterol) is a new beta 2-adrenergic agonist. Since it in itself is biologically inactive, bitolterol is considered a pro-drug. When administered it is activated within the lung by esterase hydrolysis to the active compound colterol catecholamine N-t-butyl-arterenol). In preclinical and clinical studies to date, bitolterol has proved to be an effective bronchodilator for adult and pediatric patients with chronic stable asthma and for some with chronic obstructive pulmonary disease. Bitolterol has been compared with other beta 2 agents, including isoproterenol, metaproterenol and albuterol. There is no evidence for cardiotoxicity when bitolterol is used in combination with theophylline in human studies. It is effective for control of exercise-induced asthma.     

Long-term diuretic therapy: effects of dose reduction on antihypertensive efficacy and counterregulatory systems.

In the present study, the effects of a dose reduction on antihypertensive efficacy and metabolic side effects of diuretic therapy were investigated in 36 hypertensive patients. During the first treatment period of 1 year, the patients were treated with 25 mg of the thiazide diuretic bemetizide (n = 18) or 25 mg bemetizide plus 50 mg of the potassium-sparing agent triamterene (n = 18). Mean blood pressure (BP) values decreased significantly (p less than 0.01) during the first year of the trial. Thereafter, doses were reduced to 10 mg bemetizide or 10 mg bemetizide plus 20 mg triamterene in patients whose BP became normal during the first year (n = 16 in both groups). At the end of the second year, equal BP control was achieved with doses more than twice smaller than those used during the first year. During the second year of the trial, activation of the renin-angiotensin system (RAS) was significantly less pronounced as compared with the first year and the percentage of patients with hypokalemia (less than 3.5 mM) decreased from 62.5 to 25% in the bemetizide group. Thus, this long-term study provides additional evidence that diuretics have a flat dose-response curve with respect to their antihypertensive efficacy, whereas lower doses might cause less pronounced activation of counter-regulatory systems. Furthermore, our results indicate that long-term studies might be necessary to assess the full antihypertensive potential of low doses of antihypertensive agents.     

5-Hydroxytryptophan: a review of its antidepressant efficacy and adverse effects

Alterations in serotonin metabolism may be an important factor in the etiology and treatment of depression. In this regard, 5-hydroxytryptophan (5-HTP), a serotonin precursor, has been given to patients with depression. Although a review of these studies suggests that 5-HTP possesses antidepressant properties, additional trials are clearly indicated. Following a discussion of the pharmacology of 5-HTP, the authors highlight adverse effects associated with its administration to depressed patients, neurologic subjects, and normal individuals. Relatively few adverse effects are associated with its use in the treatment of depressed patients.     

Fibrin glue: a review of its preparation, efficacy, and adverse effects as a topical hemostat

Fibrin glue is composed of two separate solutions of fibrinogen and thrombin. When mixed together, these agents mimic the last stages of the clotting cascade to form a fibrin clot. Fibrin glue is available in Europe but is not commercially available in the U.S.; therefore, investigators have extemporaneously compounded their own fibrin glue. Fibrinogen can be obtained from pooled, single-donor, and autologous blood donors and is usually isolated by the process of cryoprecipitation. The thrombin component is generally derived from commercial bovine sources. Some investigators have added calcium chloride and/or antifibrinolytics (i.e., aminocaproic acid, aprotinin) to their preparations. Fibrin glue can be applied using a double-barrel syringe or by spray application. Although fibrin glue has been used in a variety of surgical procedures, it has been especially useful in heparinized patients undergoing cardiovascular procedures requiring extracorporeal circulation, as it does not require an intact hemostatic system to be effective. Fibrin glue also has been evaluated in presealing woven or knitted Dacron vascular grafts. The major drawback to its use is the risk of transmitted serological disease from pooled and single-donor blood donors. The safest preparations use the patient's own blood to prepare fibrin glue. Overall, fibrin glue is a useful adjunct to other methods to control bleeding in selected surgical patients.     

Denosumab. Limited efficacy in fracture prevention, too many adverse effects

The standard drug for postmenopausal osteoporotic women with a high risk of fracture is alendronic acid, used in conjunction with non-drug measures. There are no drugs with demonstrated efficacy on the risk of fracture in castrated men with prostate cancer. Denosumab, a monoclonal antibody that inhibits a cytokine acting mainly on bone cells and lymphocytes, has been authorised in the European Union for use in both these settings. There are no trials comparing denosumab versus alendronic acid for symptomatic fracture prevention. In two trials involving 1189 and 504 women, the incidence of clinical fractures, recorded as simple adverse effects, did not differ significantly between the groups. In a placebo-controlled trial in about 7900 elderly osteoporotic women, denosumab significantly reduced the incidence of symptomatic vertebral fractures (0.8% versus 2.6% after 3 years) and hip fractures (0.7% versus 1.2%). An indirect comparison, providing weak evidence, suggests that denosumab is less effective than alendronic acid. In a placebo-controlled trial in 1468 castrated men with prostate cancer, denosumab did not reduce the incidence of symptomatic fractures after 3 years. Only the incidence of vertebral fractures, detected on routine radiographs, showed a statistically significant decline (1.5% versus 3.5%). Denosumab has numerous adverse effects. In placebo-controlled trials, this monoclonal antibody was associated with a higher incidence of deep-seated infections such as endocarditis, cancer, and skin rash. More data are needed on the risk of pancreatitis, long-term bone disorders (atypical fractures, delayed fracture healing, osteonecrosis of the jaw), hypocalcaemia and cataracts, all of which were reported in clinical trials. In practice, denosumab is not sufficiently effective to outweigh its established and potential risks in postmenopausal osteoporotic women or in castrated men with prostate cancer.     

Pharmacology and therapeutic effects of dehydroepiandrosterone in older subjects

Man and higher primates have adrenals that secrete large amounts of dehydroepiandrosterone (DHEA) [prasterone] and its sulphate (DHEAS) [PB 008]. A remarkable feature of plasma DHEAS levels in humans is their great decrease with aging. Researchers have postulated that this age-related decline of DHEAS levels may explain some of the degenerative changes associated with aging. Moreover, administration of DHEA to laboratory animals has demonstrable beneficial effects such as prevention of diabetes mellitus, obesity, cancer, heart disease and positive immunomodulator effects. However, in rodents DHEA(S) circulating levels are so low that it is impossible to detect any significant age-related decrease. Therefore results from rodent experiments are not relevant to human beings. Three mechanisms of action of DHEA(S) have been identified. DHEA and DHEAS are precursors of testosterone and estradiol, DHEAS is a neurosteroid which modulates neuronal excitability via specific interactions with neurotransmitter receptors and DHEA is an activator of calcium-gated potassium channels. Randomised, placebo-controlled clinical trials which included healthy individuals aged 60 years and over treated with (near) physiological doses of DHEA (50-100 mg/day) have yielded very few positive results. Impact of DHEA replacement treatment was assessed on mood, well being, cognitive and sexual functions, bone mass, body composition, vascular risk factors, immune functions and skin. The major limitations of these trials were their short duration (maximum 1 year) and the low number of study participants involved (maximum 280). Many elderly people in western countries take DHEA without medical supervision. In the US, DHEA is even classified as food supplement. At present there is no scientific evidence to recommend DHEA replacement in the elderly. Further studies are needed to form conclusions about the efficacy and the safety of DHEA replacement in elderly, and to better understand the mechanisms of action of DHEA at the molecular and cellular levels.     

Cefuroxime: antimicrobial activity, Pharmacology, and clinical efficacy

The antimicrobial activity, pharmacology, toxicity, and clinical efficacy of cefuroxime are reviewed. Cefuroxime has a second-generation cephalosporin spectrum of activity similar to cefamandole. Addition of a methoxyimino side chain has enhanced its beta-lactamase stability. Cefuroxime is active against certain cephalothin-, cefamandole-, and gentamicin-resistant bacteria. Cefuroxime has an extended half-life which allows dosing every 8 h. If penetrates into bodily tissues and fluids, including the cerebrospinal fluid, in therapeutic concentrations. Cefuroxime has been used successfully in the treatment of meningitis; sepsis; urinary tract, bone and joint, pulmonary, skin, and soft tissue infections; and gonorrhea. Competitive pricing of cefuroxime should provide a cost-effective substitute for cefamandole and, in certain situations, third-generation cephalosporins.