Biomedical subjects

L R Wiseman

Publications and source records attributed to L R Wiseman.

At least 37 records · Page 2Linked to original sources

PubMed1998

Topotecan. A review of its potential in advanced ovarian cancer.

The topoisomerase I inhibitor topotecan has shown antitumour activity against a variety of tumour types in vitro and in vivo. Topotecan in combination with drugs that induce DNA damage generally results in synergistic killing of tumour cells in vitro. As the activity of topotecan is related to exposure time, the drug is administered by intravenous infusion either continuously or once daily over a 30-minute period for several consecutive days. A 30-minute infusion of topotecan 1.5 mg/m2 on 5 consecutive days every 3 weeks produced response rates of up to approximately 20% in patients with advanced ovarian cancer who had failed to respond to platinum-based regimens or relapsed after initial response to such regimens. No significant differences in efficacy were apparent between topotecan and paclitaxel in a phase III study in patients with recurrent ovarian cancer, although a trend in favour of topotecan was evident for all major efficacy parameters. Non-cumulative myelosuppression, including neutropenia, thrombocytopenia and anaemia, is the dose-limiting toxicity associated with topotecan. Myelo-suppression was significantly more common with topotecan than with paclitaxel in a single comparative study. Non-haematological adverse events in topotecan recipients are generally mild and include alopecia, nausea, vomiting, and other gastrointestinal problems. Thus, topotecan has modest efficacy in the treatment of recurrent advanced ovarian cancer, with clinical activity similar to that of paclitaxel in a large randomised phase III study in this setting. Combinations of paclitaxel and a platinum compound are being used increasingly for first-line therapy, although relapse rates remain significant. Topotecan is therefore a suitable second-line option, providing antitumour response for some patients whose disease has relapsed after, or is refractory to, platinum-based therapy. Its wider potential when used either alone or in combination regimens should become clearer from ongoing studies.

Antineoplastic Agents↗

PubMed1998

Pexiganan acetate.

Pexiganan acetate (MSI 78) is a synthetic cationic peptide (22 amino acids) with antibacterial activity. It is an analogue of magainin 2, which is a host defence peptide isolated from frog skin. The drug is thought to act by disturbing the permeability of the cell membrane or cell wall. Pexiganan acetate has good in vitro activity against Gram-positive and Gram-negative aerobes; 99% of strains were susceptible to the agent using a break-point of 64 mg/L. 89 to 97% of anaerobes were susceptible to pexiganan acetate using the same break-point. After 7 passages in vitro, there was no evidence of resistance to pexiganan acetate among 2 strains of Staphylococcus aureus. In 2 phase III multicentre randomised double-blind trials in diabetic patients with infected foot ulcers, both topical pexiganan acetate 1% and oral ofloxacin 800 mg/day achieved clinical cure or improvement in about 90% of patients. Eradication of pathogens in the 2 studies was achieved in 82% of ofloxacin recipients and 66% of pexiganan acetate recipients at the end of therapy. Limited data indicate that pexiganan acetate is well tolerated.

Administration, Topical↗

PubMed1998

Docetaxel. A pharmacoeconomic review of its use in the treatment of metastatic breast cancer.

UNLABELLED: Advanced breast cancer has a poor prognosis (median duration of survival about 2 years); thus, treatment options are largely palliative. Recent studies with the taxoids docetaxel and paclitaxel suggest that these agents are effective second-line therapy in patients with metastatic breast cancer. Objective response rates range from 30 to 57% with docetaxel monotherapy in clinical trials in patients with advanced disease who had failed to respond to previous therapy, and the median time to disease progression ranges from 17 to 20 weeks. Currently available pharmacoeconomic data relating to docetaxel in the treatment of women with metastatic breast cancer include a cost-minimisation study and 3 cost-utility studies which relate to the UK, French and US healthcare systems. All analyses compared docetaxel with paclitaxel. Since no direct clinical comparisons of these 2 agents have been performed, model assumptions were based on available, rather than comparative, clinical data. The French model also considered vinorelbine monotherapy as a comparator. Considering direct costs only, costs associated with docetaxel ranged from < 0.3% less to 13% more than those of paclitaxel. When utilities were evaluated, docetaxel was associated with incremental gains versus paclitaxel of 33 and 75 additional days of quality-adjusted health in the UK and US studies, respectively, and 22 additional days of quality-adjusted progression-free survival (QPFS) in the French analysis. Thus, the incremental cost utility of docetaxel versus paclitaxel was an estimated Pounds 2431 per quality-adjusted life-year (QALY) in the UK analysis (1994 values) and US$8615 per QALY in the US analysis (1997 values). The French model found that docetaxel cost 700 French francs less for the extra days of QPFS (1993 costs). CONCLUSIONS: Cost-utility analyses, compiled in the absence of direct comparative data, show that docetaxel offers utility gains versus paclitaxel in the treatment of metastatic breast cancer. The incremental cost for these gains is within the accepted range for healthcare interventions.

Antineoplastic Agents, Phytogenic↗

PubMed1997

Mitoxantrone. A review of its pharmacology and clinical efficacy in the management of hormone-resistant advanced prostate cancer.

The antineoplastic agent mitoxantrone in combination with a corticosteroid (either prednisone or hydrocortisone) has shown clinical efficacy as palliative treatment for a proportion of patients (about 35 to 40%) with hormone-resistant advanced prostate cancer, a disease which predominantly affects elderly men and for which few systemic treatment options are available. Palliative end-points including pain relief, decreased analgesic use and reduced prostate specific antigen levels (a marker of tumour response) are reached in a greater percentage of patients receiving combination therapy than corticosteroid alone. In addition, there are generally greater improvements in quality-of-life parameters in mitoxantrone recipients. However, combined treatment offers no survival advantage over corticosteroid monotherapy. Neutropenia is the most common toxicity associated with mitoxantone therapy and may necessitate dosage reduction in some patients. Otherwise, mitoxantrone generally has a more favourable tolerability profile than has been established for other cytotoxic agents such as doxorubicin with regard to acute adverse events (e.g. nausea/vomiting, anorexia, constipation, alopecia, malaise/ fatigue, oedema) and cardiac toxicity. In conclusion, administration of mitoxantrone plus a corticosteroid can provide palliation for some elderly patients with hormone-resistant advanced prostate cancer, and is thus a valuable first-line treatment for this indication.

Antineoplastic Agents↗

PubMed1997

Vorozole.

Vorozole is a triazole derivative which binds to the cytochrome P450 moiety of aromatase, thus causing reversible inhibition of the enzyme. Plasma estradiol levels are reduced by about 90% in postmenopausal women treated with vorozole. Phase II clinical studies found vorozole to be an effective agent for the treatment of postmenopausal women with advanced breast cancer, achieving objective responses in up to 35% of patients. In 2 large phase III studies, vorozole 2.5 mg/day demonstrated favourable clinical efficacy compared with aminoglutethimide and megestrol. Vorozole improved patients' quality of life to a greater extent than aminoglutethimide. Clinical trials to date indicate that the tolerability of vorozole is better than that of aminoglutethimide. Vorozole also appears to be at least as well tolerated as megestrol (although inappropriate bodyweight gain is more common in megestrol recipients). The most common adverse events with vorozole are hot flushes, and nausea, which are generally mild in severity.

Anastrozole↗

PubMed1997

Intranasal fluticasone propionate. A reappraisal of its pharmacology and clinical efficacy in the treatment of rhinitis.

The intranasal corticosteroid fluticasone propionate is an effective agent for the treatment of rhinitis, demonstrating potent local anti-inflammatory activity and little, if any, systemic activity. Intranasal fluticasone propionate has shown clinical efficacy similar to that of other intranasal corticosteroids, including beclomethasone (administered at up to a 2-fold higher dosage than fluticasone), budesonide, flunisolide and triamcinolone acetonide, and provides greater relief from nasal symptoms (including nasal blockage) than antihistamine agents and intranasal sodium cromoglycate. Its efficacy in the treatment of seasonal allergic rhinitis and perennial allergic and nonallergic rhinitis has been demonstrated in large well-controlled studies in which the drug maintained adequate control of symptoms when administered in a once daily dose of 200 micrograms. In addition, fluticasone propionate has shown similar efficacy to that of beclomethasone in the treatment of nasal polyps; however, its use in the postoperative setting requires further investigation. Intranasal fluticasone propionate is well tolerated in the majority of patients, the incidence of adverse events being similar to that seen with placebo. Pharmacoeconomic analyses indicate that intranasal fluticasone propionate is significantly more cost-effective than the antihistamines terfenadine and loratadine. Overall quality of life was improved to a similar extent by fluticasone propionate and beclomethasone. In conclusion, recent clinical experience has confirmed that intranasal fluticasone propionate is a convenient, effective and well tolerated alternative to other intranasal corticosteroids and antihistamines for the treatment of rhinitis when administered once daily.

Administration, Intranasal↗

PubMed1997

Cefpirome. A review of its antibacterial activity, pharmacokinetic properties and clinical efficacy in the treatment of severe nosocomial infections and febrile neutropenia.

Cefpirome is an injectable extended-spectrum or 'fourth generation' cephalosporin. Its antibacterial activity encompasses many of the pathogens involved in hospital-acquired infections such as Enterobacteriaceae, methicillin-susceptible Staphylococcus aureus, coagulase-negative staphylococci and viridans group streptococci. Cefpirome also has in vitro activity against Streptococcus pneumoniae regardless of penicillin susceptibility. It is stable against most plasmid- and chromosome-mediated beta-lactamases, with the exception of the extended-spectrum plasmid-mediated SHV enzymes. Intravenous cefpirome 2g twice daily has shown clinical efficacy comparable to that of ceftazidime 2g 3 times daily in the treatment of hospitalised patients with moderate to severe infections. Clinical response and bacteriological eradication rates were similar in patients with severe pneumonia or septicaemia treated with either cefpirome or ceftazidime. Cefpirome appeared more effective than ceftazidime in the eradication of bacteria in patients with febrile neutropenia in 1 study; however, clinical response rates were similar in the 2 treatment groups. The tolerability of cefpirome appears similar to that of ceftazidime and other third generation cephalosporins, diarrhoea being the most frequently observed event. Thus, cefpirome is likely to be a valuable extended-spectrum agent for the treatment of severe infections. Cefpirome offers improved coverage against some Gram-positive pathogens and Enterobacteriaceae producing class I beta-lactamases compared with the third generation cephalosporins, although this has yet to be demonstrated in clinical trials.

Animals↗

PubMed1997

Toremifene. A review of its pharmacological properties and clinical efficacy in the management of advanced breast cancer.

The triphenylethylene antiestrogen toremifene is a chlorinated derivative of the antiestrogen tamoxifen, an agent which has been widely and successfully used in the treatment of breast cancer. Clinical trials investigating the efficacy of toremifene as first-line endocrine therapy in postmenopausal women with advanced breast cancer (estrogen receptor status positive or unknown) have shown this drug to have similar antitumour activity to that of tamoxifen. In multicentre comparative trials, objective responses (complete and partial) occurred in 20 to 29% of patients treated with toremifene (60 to 240 mg/day) and in 19 to 37.5% of tamoxifen (20 or 40 mg/day) recipients. The duration of response, time to disease progression and median overall survival time were generally similar in both treatment groups. Toremifene is well tolerated. Most drug-related adverse effects are mild or moderate in severity and rarely necessitate discontinuation of therapy. The tolerability profile of toremifene is similar to that reported for tamoxifen, the most common adverse effects being hot flushes, sweating, nausea and/or vomiting, dizziness, oedema, and vaginal discharge and/or bleeding. Thus, toremifene provides an equally effective and well tolerated alternative to tamoxifen for the first-line endocrine therapy of postmenopausal advanced breast cancer. Preclinical studies showing toremifene to have a lower carcinogenic potential than tamoxifen indicate that toremifene may be a preferable agent for long term treatment regimens; however, these findings require confirmation in the clinical setting.

Animals↗

PubMed1996

Formestane. A review of its pharmacological properties and clinical efficacy in the treatment of postmenopausal breast cancer.

Formestane (4-hydroxyandrostenedione) is an aromatase inhibitor which significantly reduces plasma levels of estrogen and has shown antitumour activity in postmenopausal women with breast cancer. Objective response rates in heavily pretreated patients with advanced breast cancer generally range between 20 and 30% during treatment with intramuscular formestone 250 or 500mg once every 2 weeks, and a further 20 to 30% of patients experience disease stabilisation. The median duration of response is between 8 and 14 months. Highest response rates are observed in soft tissue metastases, in patients with estrogen-responsive tumours and in those showing a response to previous endocrine therapy. Furthermore, there is some evidence to suggest that higher response rates are achieved with formestane 500 versus 250mg once every 2 weeks. In comparative studies, the clinical efficacy of intramuscular formestane 250mg did not differ significantly from that of oral megestrol when administered as second-line endocrine therapy to patients with advanced disease in whom previous tamoxifen therapy had failed. In addition, formestane produced a response rate, duration of response and overall survival rate that was not significantly different from that of oral tamoxifen when administered as first-line endocrine therapy to patients with advanced disease, but tamoxifen was superior in some measures. Further investigation of these 2 agents, including the higher dosage of formestane (500mg), is necessary to confirm their relative efficacies. Formestane is well tolerated by the majority of patients; adverse events rarely necessitate cessation of therapy. The most common adverse events are local reactions at the injection site and systemic events usually related to the effect of the drug on the hormonal milieu. The systemic tolerability of formestane is similar to that of tamoxifen but better than that of megestrol. Thus, formestane is effective and well tolerated as first-line endocrine therapy for advanced disease. However, at present, it is unlikely to challenge tamoxifen in this indication, based on recent findings from a large comparative study and the fact that formestane requires intramuscular administration. Nonetheless, formestane, which appears to have a better tolerability profile than other currently available second-line agents (including megestrol and the aromatase inhibitor aminoglutethimide), is a valuable drug for the second-line treatment of postmenopausal women with advanced breast cancer.

Androstenedione↗

PubMed1996

Ebastine. a review of its pharmacological properties and clinical efficacy in the treatment of allergic disorders.

Ebastine is a long-acting nonsedating second generation histamine H1 receptor antagonist which binds preferentially to peripheral H1 receptors in vivo. It has shown antihistamine and antiallergic activity in healthy volunteers and patients with allergies, and protected against histamine-induced bronchoconstriction in patients with asthma. Significant symptom improvement is observed in patients with seasonal or perennial allergic rhinitis or chronic idiopathic urticaria following administration of ebastine 10 mg/day, or 20 mg/day in severe rhinitis. In clinical trials, the efficacy of ebastine 10 or 20 mg/day was generally similar to standard dosages of terfenadine, cetirizine, astemizole and loratadine in patients with seasonal allergic rhinitis, astemizole, terfenadine and ketotifen in patients with chronic idiopathic urticaria, and ketotifen, terfenadine, chlorpheniramine and mequitazine in patients with perennial allergic rhinitis. The most frequent adverse events reported during ebastine therapy are drowsiness, headache and dry mouth, the incidence being similar to that reported in placebo recipients. Serious adverse cardiac events, observed on rare occasions with some other histamine H1 receptor antagonists, have not been reported with ebastine, and there has been no evidence of QTc interval prolongation related to ebastine therapy. Thus, once-daily ebastine offers an effective and well-tolerated alternative to other second generation antihistamines in current use for the first-line treatment of seasonal and perennial allergic rhinitis and chronic idiopathic urticaria.

Animals↗

PubMed1996

Secnidazole. A review of its antimicrobial activity, pharmacokinetic properties and therapeutic use in the management of protozoal infections and bacterial vaginosis.

Secnidazole is structurally related to the commonly used 5-nitroimidazoles metronidazole and tinidazole. These drugs share a common spectrum of activity against anaerobic micro-organisms and they appear particularly effective in the treatment of amoebiasis, giardiasis, trichomoniasis and bacterial vaginosis. Secnidazole is rapidly and completely absorbed after oral administration and has a longer terminal elimination half-life (approximately 17 to 29 hours) than commonly used drugs in this class. in patients with intestinal amoebiasis or giardiasis, clinical or parasistological cure rates of 80 to 100% are achieved after treatment with a single dose of secnidazole 2g (30 mg/kg in children), similar to the response rates achieved with multiple dosage regimens of metronidazole or tinidazole. Patients with hepatic amoebiasis appears to respond well to 5- to 7-day therapy with secnidazole, but the efficacy of this drug regimen requires further evaluation in larger numbers of patients. After administration of a single dose of secnidazole, parasitological eradication was achieved in approximately 92 to 100% of patients with urogenital trichomoniasis. Patients with bacteria vaginosis respond at least as well to a single dose of secnidazole as to single-dose tinidazole, or single- or 7-day treatment with metronidazole; clinical improvement and/or microbiological evidence of cure was attained in approximately 59 to 96% of patients. In the clinical trials reviewed, secnidazole was well tolerated; most adverse events were gastrointestinal in nature and did not require treatment intervention or withdrawal from therapy. In summary, available evidence suggests that secnidazole is as efficacious as other 5-nitroimidazole drugs in the treatment of protozoal infections and bacterial vaginosis. The convenience and ease of administration associated with single-dose therapy, combined with a good tolerability profile, make secnidazole a suitable option to other single-dose treatments and an attractive alternative to multiple dosage regimens with other drugs in this class.

Absorption↗

PubMed1996

Aceclofenac. A review of its pharmacodynamic properties and therapeutic potential in the treatment of rheumatic disorders and in pain management.

Aceclofenac is a phenylacetic acid derivative with anti-inflammatory and analgesic properties similar to those of diclofenac. However, preclinical studies suggest that the potential of aceclofenac to cause gastrointestinal damage is less than that of diclofenac. Double-blind comparative trials indicate that the efficacy of aceclofenac is at least equivalent to that of ketoprofen and similar to that of indomethacin and diclofenac in patients with rheumatoid arthritis, similar to that of diclofenac and piroxicam in patients with osteoarthritis of the knee and similar to that of tenoxicam, indomethacin and naproxen in patients with ankylosing spondylitis. The analgesic efficacy of aceclofenac 100mg is more prolonged than that of paracetamol (acetaminophen) 650mg. If the apparently improved gastrointestinal tolerability of aceclofenac compared with diclofenac is confirmed by wider clinical experience, aceclofenac will have the potential to become a preferred initial drug in an individualised NSAID regimen in patients with rheumatic disorders.

Animals↗

PubMed1996

Irinotecan. A review of its pharmacological properties and clinical efficacy in the management of advanced colorectal cancer.

Irinotecan (CPT-II) is a semisynthetic derivative of camptothecin. It and other camptothecin analogues/derivatives appear to exert their antitumour activity by binding to topoisomerase I. The active metabolite of irinotecan, 7-ethyl-10-hydroxycamptothecin (SN-38), has demonstrated potent growth inhibition of human colorectal cancer cells in vitro, with superior activity to fluorouracil. In phase II clinical studies in patients with advanced colorectal cancer, objective response rates after irinotecan therapy ranged between 20.5 and 32%. These studies used a range of irinotecan regimens including 350 mg/m2 once every 3 weeks (Europe), 125 to 150 mg/m2 once a week for 4 weeks followed by a 2-week drug-free interval (US) and 100 mg/m2/week or 150 mg/m2 every 2 weeks (Japan). The median duration of response ranged between 5.6 and 10.6 months. Disease stabilisation occurred in 30 to 71.2% of patients. Objective response rates to irinotecan therapy in patients who had received no prior chemotherapy were similar to those in patients pretreated with fluorouracil. Importantly, irinotecan also induced responses in some patients with tumours refractory to fluorouracil. Severe (grade 3 or 4) neutropenia and diarrhoea, which occurred in up to 40% of patients receiving irinotecan therapy in phase II studies, require careful monitoring and appropriate management. Thus, irinotecan is a valuable agent for the second-line treatment of patients with advanced colorectal cancer who fail to respond to or relapse after fluorouracil therapy.

Antineoplastic Agents, Phytogenic↗

PubMed1995

Oral pilocarpine: a review of its pharmacological properties and clinical potential in xerostomia.

Pilocarpine is a cholinergic agonist which stimulates salivary secretion both in individuals with normal salivary gland function and in those with impaired salivary flow (xerostomia or oral dryness). A rapid increase in salivary flow rate is observed following oral pilocarpine administration and peak levels are maintained for at least 1 to 2 hours. Mean salivary flow rates after administration of pilocarpine are 2- to 10-fold higher than after placebo, and no evidence of tolerance to the pharmacological effects of the drug has been observed during prolonged administration for up to 5 months. The clinical efficacy of oral pilocarpine in relieving symptoms of xerostomia (resulting from radiation therapy to the head and neck region or salivary gland dysfunction), including oral dryness and difficulty in chewing, swallowing and speaking, has been demonstrated in double-blind placebo-controlled clinical trials. In these studies, pilocarpine 5 to 10mg 3 times daily increased salivary flow and improved symptoms of xerostomia in a significantly higher percentage of patients than did placebo (54 versus 25% in one study). Preliminary findings indicate that administration of pilocarpine during radiation therapy may reduce the severity of xerostomia; however, this requires further investigation. The majority of patients receiving oral pilocarpine therapy for xerostomia experience adverse events (most commonly sweating); however, these are generally mild and tolerable in nature. Thus, pilocarpine is an effective agent for the treatment of xerostomia, increasing salivary flow and reducing symptom severity to a significantly greater extent than placebo. Further clinical trials should evaluate the potential beneficial effects of pilocarpine on the incidence of dental caries and oral candidiasis during prolonged therapy, its prophylactic efficacy during radiation therapy and its efficacy relative to that of other salivary stimulants.

Controlled Clinical Trials as Topic↗

PubMed1995

Meropenem. A review of its antibacterial activity, pharmacokinetic properties and clinical efficacy.

The parenteral carbapenem meropenem is relatively stable to inactivation by human renal dehydropeptidase (DHP-1) and does not require concomitant administration of a DHP-1 inhibitor such as cilastatin. It has a broad spectrum of antibacterial activity in vitro, the majority of Gram-negative, Gram-positive and anaerobic pathogens being highly susceptible to the drug. Meropenem has shown clinical and bacteriological efficacy in the treatment of a wide range of serious infections in adults and children which is at least comparable with that of currently available treatment options. Its clinical and bacteriological efficacy is similar to that of imipenem/cilastatin, clindamycin plus tobramycin and cefotaxime plus metronidazole in the treatment of intraabdominal infections; cefotaxime or ceftriaxone in the treatment of meningitis; imipenem/cilastatin, and ceftazidime with or without an aminoglycoside, in lower respiratory tract infections; and imipenem/cilastatin or ceftazidime in the treatment of urinary tract infections. Satisfactory clinical and bacteriological response rates have also been achieved in patients with skin and skin structure infections, obstetric and gynaecological infections or septicaemia, and in immunocompromised patients with febrile episodes. Preliminary findings also indicate efficacy in the treatment of respiratory tract infections in patients with cystic fibrosis. The tolerability profile of meropenem is generally similar to that of comparator agents, although it is associated with a lower incidence of adverse gastrointestinal effects (nausea and vomiting) than imipenem/cilastatin. Importantly, the incidence of seizures in patients with meningitis is not increased following administration of meropenem. Thus, meropenem is an effective broad spectrum antibacterial drug for the treatment of a wide range of infections including polymicrobial infections in both adults and children, with comparable efficacy to imipenem/cilastatin and various other treatment regimens. Meropenem is likely to be of greatest value as empiric monotherapy in the treatment of serious infections for those caused by multiply-resistant pathogens. Further clinical experience is necessary, however, to ultimately define its place in therapy.

Absorption↗

PubMed1994

Ciprofloxacin. A review of its pharmacological profile and therapeutic use in the elderly.

Ciprofloxacin belongs to the fluoroquinolone class of antimicrobial agents which primarily inhibit bacterial DNA gyrase. It is effective after oral or intravenous administration, demonstrating potent antibacterial activity against most Gram-negative, and many Gram-positive bacteria. Although most bacterial strains have remained susceptible to the drug, low rates of resistance have been observed in some strains of Pseudomonas aeruginosa and enterococci and higher rates in methicillin-resistant Staphylococcus aureus. Ciprofloxacin attains concentrations in most tissues and body fluids sufficient to inhibit the majority of susceptible pathogens. Its pharmacokinetic profile in the elderly (> or = 65 years) is broadly similar to that reported in younger persons, although plasma concentrations are higher, and renal clearance is decreased in elderly persons. Ciprofloxacin is an effective treatment for those infections most common in elderly patients, including infections of the urinary tract, lower respiratory tract, skin and soft-tissues, and bone and joints, and is an effective agent for prophylaxis in transurethral surgery. Orally administered ciprofloxacin appeared to be at least as effective as alternative orally administered antimicrobial agents (trimethoprim, cotrimoxazole [trimethoprim/sulfamethoxazole], amoxicillin, amoxicillin/clavulanic acid) and also as effective as various parenteral agents (ceftriaxone, cefamandole, ceftazidime, cefotaxime) in a small number of comparative clinical trials. However, further studies are needed to clarify the comparative efficacy of ciprofloxacin with that of other oral and parenteral agents in the elderly. Initial trials have also indicated therapeutic efficacy of oral ciprofloxacin in malignant external otitis and bacterial prostatitis. Nevertheless, with its good tolerability profile and potent antimicrobial activity following oral administration, ciprofloxacin appears to offer a valuable alternative for treating various acute and chronic infections in elderly patients. Causative pathogens are frequently multiresistant in this patient group, and ciprofloxacin avoids or minimises the need for parenteral therapy.

Bacterial Infections↗

PubMed1994

Transdermal estradiol/norethisterone. A review of its pharmacological properties and clinical use in postmenopausal women.

The combined transdermal estradiol/norethisterone therapeutic system is designed to deliver both estradiol and norethisterone into the systemic circulation at a constant rate for up to 4 days when affixed to the skin. Transdermal administration avoids hepatic first-pass metabolism, allowing therapeutic concentrations of the progestogen and estrogen to be maintained in postmenopausal women following low dose administration. Transdermal norethisterone does not appear to alter the potentially beneficial effects of transdermal estradiol on total cholesterol, low-density lipoprotein (LDL) or triglyceride levels, or metabolic parameters of bone resorption or vaginal cytology. Protection of the endometrium from the effects of unopposed estradiol is achieved by sequential treatment with transdermal estradiol/norethisterone for 2 weeks of each 28-day cycle, and the majority of patients experience a regular vaginal bleeding pattern with this treatment regimen. Menopausal symptoms are improved to a similar extent during the transdermal estradiol-only and combined estradiol/norethisterone treatment phases. The transdermal therapeutic system has been well accepted by patients in clinical trials. It is generally well tolerated, the most common adverse effect being local irritation at the site of application. Estrogen- and progestogen-related systemic adverse events are reported in a small proportion of patients. Thus, the combined estradiol/norethisterone transdermal delivery system offers a more convenient and consistent method of progestogen administration. Together with its therapeutic efficacy when administered at lower dosages than oral therapy, it is likely to further improve patient compliance during hormone replacement therapy.

Administration, Cutaneous↗

PubMed1994

Cisapride. An updated review of its pharmacology and therapeutic efficacy as a prokinetic agent in gastrointestinal motility disorders.

Cisapride is an orally administered prokinetic agent which facilitates or restores motility throughout the length of the gastrointestinal tract. It is a substituted piperidinyl benzamide, chemically related to metoclopramide, but unlike metoclopramide, cisapride is largely devoid of central depressant or antidopaminergic effects. In placebo-controlled trials, cisapride improved healing rates and symptoms in both adults and children with reflux oesophagitis. Maintenance therapy with cisapride at half the healing dose is effective in reducing the incidence of relapse. Symptoms are also alleviated in patients with functional dyspepsia, and gastric emptying and symptoms are improved in most patients with gastroparesis, an effect which is sustained during long term administration. However, the efficacy of cisapride in end-stage gastroparesis remains less clear. Cisapride increases stool frequency in patients with chronic constipation, and limited data suggest that the drug may also be beneficial in treating chronic intestinal pseudo-obstruction and irritable bowel syndrome. Cisapride demonstrated efficacy comparable with or superior to that of metoclopramide, and was at least as effective as cimetidine and ranitidine in patients with reflux disease. In patients with functional dyspepsia, cisapride has shown at least equal efficacy to domperidone, metoclopramide and ranitidine, and superior efficacy to cimetidine in the small comparative trials conducted to date. Adverse effects in patients receiving cisapride are generally transient and mild, with abdominal cramping, borborygmi, diarrhoea or loose stools most frequently reported. Central nervous system adverse effects are rare. Thus, with its favourable tolerability profile and demonstrated efficacy in a variety of gastrointestinal motility disorders, the position of cisapride as a valuable agent in the management of patients with gastrointestinal motility disorders is strengthening. However, larger well-controlled comparative trials of the drug with other agents are necessary before the relative position of cisapride in therapy can be categorically defined.

Animals↗