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At least 55 records · Page 3Linked to original sources
PubMed1994

Evaluation of the 3-drug combination, Rifater, versus 4-drug therapy in the ambulatory treatment of tuberculosis in Cape Town.

The subjective impression among clinicians that the use of Rifater was causing delayed sputum conversion and increased drug resistance was tested in a prospective study. Adults in the Cape Town municipal area with a first episode of pulmonary tuberculosis were treated either with Rifater or a regimen consisting of isoniazid, rifampicin, pyrazinamide and ethambutol. All patients who took the treatment as prescribed (67 Rifater, 39 the 4-drug regimen) converted to a negative sputum culture by the time 90 doses had been taken. The rates of inadequate compliance and of side-effects were similar in the two groups. Drug sensitivity testing of bacteria cultured from pre-treatment sputum specimens revealed an overall primary resistance rate of 4.84% in the population studied, sufficiently low to preclude any necessity for routine pre-treatment drug sensitivity testing.

Antitubercular Agents↗
PubMedDate not supplied

Developing artemisinin based drug combinations for the treatment of drug resistant falciparum malaria: A review.

The emergence and spread of drug resistant malaria represents a considerable challenge to controlling malaria. To date, malaria control has relied heavily on a comparatively small number of chemically related drugs, belonging to either the quinoline or the antifolate groups. Only recently have the artemisinin derivatives been used but mostly in south east Asia. Experience has shown that resistance eventually curtails the life-span of antimalarial drugs. Controlling resistance is key to ensuring that the investment put into developing new antimalarial drugs is not wasted. Current efforts focus on research into new compounds with novel mechanisms of action, and on measures to prevent or delay resistance when drugs are introduced. Drug discovery and development are long, risky and costly ventures. Antimalarial drug development has traditionally been slow but now various private and public institutions are at work to discover and develop new compounds. Today, the antimalarial development pipeline is looking reasonably healthy. Most development relies on the quinoline, antifolate and artemisinin compounds. There is a pressing need to have effective, easy to use, affordable drugs that will last a long time. Drug combinations that have independent modes of action are seen as a way of enhancing efficacy while ensuring mutual protection against resistance. Most research work has focused on the use of artesunate combined with currently used standard drugs, namely, mefloquine, amodiaquine, sulfadoxine/pyrimethamine, and chloroquine. There is clear evidence that combinations improve efficacy without increasing toxicity. However, the absolute cure rates that are achieved by combinations vary widely and depend on the level of resistance of the standard drug. From these studies, further work is underway to produce fixed dose combinations that will be packaged in blister packs. This review will summarise current antimalarial drug developments and outline recent clinical research that aims to bring artemisinin based combinations to those that need them most.

Animals↗
PubMed1993

Comparison of single and combination drug treatment strategies in experimental brain trauma.

Effects of single-drug and combination drug treatments were examined in a model of lateral fluid percussion-induced traumatic brain injury (TBI) in rats. Treatments included the opioid receptor antagonist nalmefene, the thyrotropin releasing hormone (TRH) analog YM14673, the noncompetitive N-methyl-D-aspartate (NMDA) antagonist dextrorphan, nalmefene + dextrorphan, YM14673 + nalmefene, YM14673 + dextrorphan, and equal volume saline. Single-dose treatment with nalmefene, YM14673, or dextrorphan at 30 min after trauma each significantly improved behavioral recovery at two weeks as compared with vehicle-treated controls, confirming earlier studies with these agents. No combination treatment was superior to treatment with the most effective individual drug alone. Combination treatment with the TRH analog and the NMDA antagonist resulted in significantly less effectiveness than treatment with either drug alone. These findings indicate the need for preclinical studies to examine potential drug-drug interactions in the treatment of central nervous system (CNS) trauma.

Animals↗
PubMed1987

Treatment of porcine Pseudomonas ARDS with combination drug therapy.

A combination drug therapy (Poly-5: ibuprofen 12.5 mg/kg, methylprednisolone 30 mg/kg, cimetidine 150 mg, diphenhydramine 10 mg/kg, and ketanserin 0.2 mg/kg) given at 20 and 120 minutes after starting continuous intravenous Pseudomonas (Ps, 5 X 10(8) CFU/20 kg/min) was studied in three groups of swine: saline control (C, n = 9), Ps alone (Ps, n = 8), and Ps plus Poly-5 (n = 5). PaO2, systemic (SAP) and pulmonary arterial (PAP) pressures, cardiac index (CI), thermal-cardiogreen extravascular lung water (EVLW), pulmonary albumin flux (slope index, SI), and arterial blood serotonin levels (5-HT) were measured. Ps produced significant (p less than 0.05) increases in PAP, EVLW, and SI with decreases in PaO2, CI, and SAP. 5-HT fell significantly compared to baseline. Poly-5 prevented (p less than 0.05) the rise in EVLW and SI and the fall in PaO2 and CI compared to Ps. PAP and SI were maintained at C until 90 and 150 minutes, respectively. SAP fell significantly from C at 30, 60, and 180 minutes. 5-HT was significantly lower than Ps throughout, and significantly lower than baseline at 180 minutes. Combined blockade of arachidonic acid metabolites, histamine, and serotonin receptors prevented hypoxemia, increased pulmonary capillary permeability, and cardiovascular deterioration in this porcine septic ARDS model.

Animals↗
PubMed2006

Development and assessment of conventional and targeted drug combinations for use in the treatment of aggressive breast cancers.

Combination chemotherapy has been at the forefront of cancer treatment for over 40 years. However, the rationale for selecting drug combinations and the process used to demonstrate clinical effectiveness has primarily followed trial and error methodology. Typically, the selection and assessment of combined drug therapies has been based on the effectiveness of each agent as monotherapy in treating the neoplasm and avoiding overlapping toxicities, followed by clinical trials to establish dose scheduling, toxicity, and efficacy. Unfortunately, this scheme is inefficient in terms of the time required to complete and revise these clinical trials based on the outcome to optimize the drug combination. A more rational approach for the development of combination oncology products should consider (i) in vitro assays for assessing therapeutic effects of drug combinations (antagonistic, additive or synergistic interactions) when added simultaneously; (ii) methods for measuring these interactions in vivo; (iii) the importance of understanding pharmacokinetic and biodistribution parameters when using drug combinations; (iv) the need to assess pathways known to contribute to cancer cell survival as well as metastasis; and (iv) the need to assess the fate of different cell populations (cancer and stroma) contributing to the development of cancer. Therefore, the goal of this article is to provide a road map for the preclinical development of drug combination products that will have improved therapeutic activity and a high likelihood of providing beneficial therapeutic outcomes in patients with aggressive cancers with a specific focus on patients with breast cancer.

Animals↗
PubMedDate not supplied

Fixed-drug combinations as first-line treatment for hypertension.

As combinations of drugs from different classes that have synergistic or additive effect and properties to cancel out each others' untoward hemodynamic and metabolic effects become more and more widely used, their use as first-line therapy for the treatment of newly diagnosed hypertensive patients is growing in popularity as well. The possibility to begin therapy with a fixed 2-drug combination may be preferable to starting with monotherapy followed by upward titration and addition of other agents. More and more combinations are coming out on the market and proving their effectiveness in randomized controlled trials and in large multicenter studies. One suggestion is the "polypill," a fixed combination of multiple agents that address various components of the metabolic syndrome and coexisting common risk factors in both high-risk patients with conditions requiring polypharmacy, and in healthy asymptomatic individuals.

Antihypertensive Agents↗
PubMed2006

Enhanced antiscrapie effect using combination drug treatment.

Combination treatment with pentosan polysulfate and Fe(III)meso-tetra(4-sulfonatophenyl)porphine in mice beginning 14 or 28 days after scrapie inoculation significantly increased survival times. This increase may be synergistic, implying that the compounds act cooperatively in vivo. Combination therapy may therefore be more effective for treatment of transmissible spongiform encephalopathies and other protein-misfolding diseases.

Animals↗
PubMed1980

Sustained remission of choriocarcinoma with cis-platinum, vinblastine, and bleomycin after failure of conventional combination drug therapy.

Combination chemotherapy with methotrexate, actinomycin D. and an alkylating agent (MAC) has become widely used for patients with "high-risk" gestational choriocarcinoma. When such chemotherapy fails to obliterate this disease the prognosis has been uniformly poor. Chemotherapy failure may result from excessive toxicity or tumor resistance. Two patients are presented who failed treatment with MAC. Both have achieved sustained clinical and serum beta subunit-hCG titer remission of choriocarcinoma with the use of the drugs cis-platinum, vinblastine, and bleomycin.

Adult↗
PubMed1983

Chemotherapeutic study on Yoshida sarcoma ascites cells implanted into the glandular stomach of rats. Monotherapy with 5-fluorouracil, methyl-CCNU, mitomycin C, adriamycin, and cytosine arabinoside, and combination therapy with respective two-drug combinations.

The chemotherapeutic activity of five cytostatic drugs was investigated experimentally in monotherapy and in two-drug combinations, using Yoshida sarcoma cells implanted into the wall of the glandular stomach of Sprague-Dawley rats. In monotherapy, the antibiotic agent mitomycin C and the nitrosourea methyl-CCNU exhibited the highest cytotoxic activity in this tumor model. In combination therapy, the combination of these two drugs was superior to all the other therapeutic schemes tested. In general, the results demonstrate a marked superiority of combination therapy in comparison with monotherapy.

Animals↗
PubMedDate not supplied

Lovastatin and extended-release niacin combination product: the first drug combination for the management of hyperlipidemia.

Advicor (lovastatin and extended-release niacin) is the first cholesterol-lowering combination product to become available for the management of hyperlipidemia. Lovastatin significantly lowers low-density lipoprotein cholesterol, whereas niacin significantly lowers triglycerides and lipoprotein (a) and markedly increases high-density lipoprotein cholesterol. These effects are ideal for managing a variety of lipid disorders, including metabolic syndrome. Lovastatin and niacin reduce coronary heart disease mortality in primary and secondary prevention patients, respectively. The extended-release niacin component uses a unique technology to minimize adverse effects (e.g., flushing and hepatotoxicity) while retaining the same lipid-altering effects as immediate-release niacin. The combination product appears to be well tolerated, with discontinuation due to adverse effects other than flushing occurring in a similar percent of patients as for lovastatin in clinical trials. Approximately 9% of patients discontinued the combination product due to flush. No confined cases of myopathy or hepatotoxicity have been reported with this product. Once-daily dosing provides ease of administration that should improve compliance and result in a greater proportion of patients meeting their low-density lipoprotein cholesterol goals. The nomenclature surrounding niacin products used to treat dyslipidemias is confusing. While only two types of niacin formulations exist (immediate-release formulations and formulations which dissolve more slowly than immediate-release formulations), government regulations allow for slowly dissolved niacin formulations to be divided into two types of niacin products; those that are available over-the-counter (OTC) and those that are available by prescription only. Over-the-counter slowly dissolved niacin preparations are not classified as OTC per se, but are considered "nutritional supplements". For this reason, they fall under the jurisdiction of the Federal Trade Commission and do not fall under the umbrella of the FDA branch that controls dyslipidemic products (Endocrine and Metabolic Division of the Center for Drug Evaluation and Research). The slowly dissolved niacin nutritional supplements have not been reviewed by the FDA for safety nor efficacy in the treatment of dyslipidemia nor are they required to meet generic drug rules (even though various brands are available). These brands are described on their labels as "sustained-release", "timed-release", and "slow-release" for example. Only two slowly absorbed niacin products have been approved by the FDA for the treatment of dyslipidemia; they are Niaspan (Kos Pharmaceuticals, Inc., Miami, FL) and Advicor (Kos Pharmaceuticals, Inc., Miami, FL). The term "extended-release" has been given to these two products to simplify the terminology and differentiate the products from immediate-release niacin. In this review, we will use "extended-release" to refer to the FDA approved slowly dissolving niacin preparation and "sustained-release" to refer to the nutritional supplements (not FDA approved).

Clinical Trials as Topic↗
PubMed2006

Poly(ethylene-co-vinyl acetate) copolymer matrix for delivery of chlorhexidine and acyclovir drugs for use in the oral environment: effect of drug combination, copolymer composition and coating on the drug release rate.

OBJECTIVES: This study utilizes a bio-compatible ethylene vinyl acetate (EVA) copolymer to deliver drugs at therapeutic levels over extended periods of time. The release rate of an anti-fungal and an anti-microbial drug namely acyclovir (ACY) and chlorhexidine diacetate (CDA) from EVA was investigated individually and as a mixture. The effect of drug combination, the composition of the copolymer and the coating of the matrix with a different polymer on the rate of drug release are presented. METHOD: Polymer casting solutions were prepared by homogeneously dissolving EVA copolymer and the drugs in the ratio (40:1) in dichloromethane. The drugs ACY and CDA were used individually as well as in three different weight ratios maintaining the total drug concentration in the polymer at 2.5%. Different concentrations of vinyl acetate (VA) 28, 32 and 40% in the EVA matrix were used to study the release of either ACY or CDA alone while 40% VA was used for the release study of the individual drug as well as their mixtures. Thin square films of 3cmx3cm with a thickness of 0.7mm were cut from the dry sheet obtained by solvent evaporation. Coated films were prepared by dipping ACY and CDA drug-loaded EVA films (VA 40%) into EVA copolymer of VA 32% and then dried. All of the drug-loaded samples were extracted at 37 degrees C in 10ml distilled water that was replaced daily. The rate of individual drug release was measured by UV-spectrophotometer while the mixtures of drugs were measured by high performance liquid chromatography (HPLC). RESULTS: The release rate of ACY is higher than that of CDA both individually and in the ACY/CDA 50/50 mixture. In the other mixtures, the release of the drug is proportional to its concentration in the mixture. Total release of ACY is higher than CDA in most compositions. The effect of increasing the vinyl acetate content of the EVA matrix increased the drug release rate (p=0.02) while coating of films resulted in a decrease of the release rate of the drugs. SIGNIFICANCE: Measurements of the in vitro rate of drug release showed that there was a sustained release of drug at an almost constant concentration over extended period of time, thus providing a basis for oral treatment modality. We show that it is possible to alter the rate of drug release in the EVA matrix to a desired value by: (1) changing the composition of the EVA copolymer, (2) altering the mixtures of drugs and (3) coating the matrix with additional polymer. The use of mixtures of drugs that can enhance or decrease the rate of drug release may prove more effective in treating persistent oral infections in immunocompromised patients.

Acyclovir↗
PubMed1988

Susceptibility of Mycobacterium avium complex to various two-drug combinations of antituberculosis agents.

The drug susceptibility of two untypable strains of Mycobacterium avium complex were studied in 7H10 agar plates containing ethambutol (EMB), isoniazid (INH), rifampicin (RMP), ethionamide (ETH), and streptomycin (SM) alone and in two-drug combinations. The effective dose inhibiting 75% of the mycobacterial population (ED 75) was estimated by a regression analysis on the probit transformed inhibition percentages and plotted on an isobologram for each combination. No major discrepancies were found between strains. Five combinations (RMP plus INH, RMP plus EMB, EMB plus SM, INH plus EMB, and ETH plus INH) showed synergistic effect, whereas five other combinations (ETH plus EMB, ETH plus RMP, ETH plus SM, SM plus RMP, and SM plus INH) showed antagonistic effect. These in vitro results are not in combination with the known results of treatment of the M. avium diseases. We conclude that the effect of drug combinations against M. avium may be strain dependent and that it is important to determine this effect in vitro before setting up a treatment protocol.

Aged↗
PubMed1982

Antiarrhythmic drug combinations in the treatment of ventricular tachycardia.

Combinations of antiarrhythmic drugs are frequently used to treat refractory ventricular tachycardia (VT), but few scientific data support this practice. We examined the efficacy and electrophysiology of 110 antiarrhythmic drug combination trials at electrophysiologic study in 74 patients with recurrent ventricular tachycardia. Lidocaine was combined with quinidine in 33 trials, procainamide in 22 and encainide in 20. Propranolol was combined with quinidine in 17 trials, procainamide in 12 and encainide in six. All individual drugs tested (except propranolol, which was usually not tested individually) had failed at electrophysiologic study or clinically in the presence of usually accepted plasma concentrations. Lidocaine in combination with quinidine was effective in 3% of the trials, with procanamide in 5% and with encainide in none of the trials. Propranolol in combination with quinidine was effective in 18% of the trials, with procainamide in 17% and with encainide in none of the trials. The electrophysiologic effects of the tested drug combinations were dominated by the individual effects of the type 1 antiarrhythmic agents. We conclude that the tested antiarrhythmic drug combinations are infrequently effective in preventing VT induction at electrophysiologic study when each agent has failed individually. The addition of lidocaine or propranolol to quinidine, procainamide or encainide does not produce significant synergistic or new effects on the electrophysiologic variables analyzed.

Aged↗
PubMed1991

Effect of drug combinations on bilirubin-albumin binding.

Drugs which compete with bilirubin for albumin binding may increase the risk of kernicterus. Fortunately, few drugs are strong competitors. However, in neonatology, many drugs are used simultaneously. We have studied the effect of drug combinations on bilirubin binding using human serum albumin and the peroxidase method. Combinations of aminophylline with phenobarbital, cefotaxime and vancomycin were studied as well as the combination of vancomycin and cefotaxime. The results show that the bilirubin-displacing effect of the drug combinations cannot be predicted from each drug's individual effect. These results are consistent with a flexible model of albumin binding. Combinations of drugs which are both albumin-bound and reach high serum concentrations should be tested for their combined effect on bilirubin binding and this information used in deciding on treatment in sick, premature infants.

Aminophylline↗
PubMed2003

The development of combination drugs for atherosclerosis.

The complexity of medical care has led to a dramatic increase in the number of drugs taken by patients. In an effort to improve patient compliance and the effectiveness of clinical care, many drugs are being studied for combination in a single capsule or tablet. The recent success of many combination drugs for hypertension has accelerated the interest in combination drugs for lipids and atherosclerosis. Advicor (Kos Pharmaceuticals, Miami, FL), a combination of nicotinic acid and a statin (mevacor), is the first combination lipid drug. Recently, the United States Food and Drug Administration approved the combination of another statin, pravachol, with aspirin. Therefore, combination drugs are likely to be a significant contribution to clinical practice and drug development.

Arteriosclerosis↗
PubMed1988

Combination drug therapy for familial combined hyperlipidemia.

STUDY OBJECTIVE: To compare the efficacy of gemfibrozil and colestipol with gemfibrozil and lovastatin in patients with familial combined hyperlipidemia. DESIGN: A prospective, randomized trial. SETTING: An outpatient clinical research center in a tertiary care center. PATIENTS: Seventeen patients with familial combined hyperlipidemia documented by studies of first-degree relatives; nine patients with type 2b hyperlipoproteinemia, and eight patients with type 4 hyperlipoproteinemia. INTERVENTIONS: Baseline lipid, lipoprotein, and apolipoprotein levels were obtained during control periods on diet alone and on gemfibrozil therapy. Patients then received gemfibrozil and colestipol or gemfibrozil and lovastatin in a randomized order. MEASUREMENTS AND MAIN RESULTS: In patients with type 2b hyperlipoproteinemia, gemfibrozil alone significantly reduced total cholesterol by 11%, and low density lipoprotein (LDL)-apolipoprotein B by 18%, did not change LDL-cholesterol, and raised high density lipoprotein (HDL)-cholesterol levels by 26%. Addition of either colestipol or lovastatin reduced LDL-cholesterol levels by 17% and 25%, respectively, compared to gemfibrozil alone. However, colestipol mitigated the HDL-cholesterol raising effect of gemfibrozil and did not further reduce LDL-apolipoprotein B levels. In contrast, addition of lovastatin caused an additional reduction of LDL-apolipoprotein B 19% compared with gemfibrozil alone. In patients with type 4 hyperlipoproteinemia, gemfibrozil alone reduced triglycerides by 40%, raised HDL-cholesterol by 26%, and increased LDL-cholesterol levels by 29%. The addition of either colestipol or lovastatin reduced LDL-cholesterol levels by 34% and 33%, respectively (compared with gemfibrozil alone), but greater reductions of LDL-apolipoprotein B (30% with lovastatin compared with 15% with colestipol, compared with gemfibrozil alone), and increases in HDL-cholesterol levels (8% increase with lovastatin compared with 10% decrease with colestipol, compared to gemfibrozil alone) were seen with the lovastatin combination. CONCLUSIONS: Although gemfibrozil with either colestipol or lovastatin favorably altered lipoprotein levels in patients with hypertriglyceridemia and familial combined hyperlipidemia, the combination of gemfibrozil and lovastatin appeared superior overall.

Adult↗
PubMed1975

Combination drug therapy for the psychogeriatric patient: comparison of dosage levels of the same psychotropic drugs, used singly and in combination.

The dosage levels for a number of frequently prescribed psychotropic drugs, used singly or in combination, were determined in 902 long-term psychogeriatric hospital patients. The data failed to support the hypothesis that physicians prescribe lower dosages when combination therapy is used. Rather, the tendency was toward higher dosages under these circumstances.

Aged↗