Biomedical subjects

Danial E Baker

Publications and source records attributed to Danial E Baker.

18 recordsLinked to original sources

PubMed2006

Exenatide: an incretin mimetic for the treatment of type 2 diabetes mellitus.

BACKGROUND: Exenatide is a subcutaneously injected incretin mimetic. It is indicated as adjunctive therapy to improve glycemic control in patients with type 2 diabetes mellitus (T2DM) who are already receiving therapy with metformin, a sulfonylurea, or both but continue to have suboptimal glycemic control. OBJECTIVE: This article reviews available information on the clinical pharmacology, comparative efficacy, tolerability, drug interactions, contraindications and precautions, dosage and administration, availability and storage, and cost of exenatide. METHODS: MEDLINE (1966-April 2006) and Web of Science (1995-April 2006) were searched for original research and review articles published in the English language. The search terms used were exenatide, exendin-4, glucagon-Like peptide-1, GLP-1, and incretin mimetic. The reference lists of identified articles were also consulted, as was selected information from the package insert for exenatide. All relevant comparative efficacy studies that were available in published form were included in the review. RESULTS: Naturally occurring incretins, such as glucagon-like peptide-1 (GLP-1), exhibit insulinotropic properties after release into the circulation from the gut. As a GLP-1 agonist, exenatide improves glucose homeostasis by mimicking the actions of naturally occurring GLP-1. It improves glycemic control by reducing fasting and postprandial glucose concentrations through a combination of known mechanisms, including glucose-dependent insulin secretion, restoration of first-phase insulin response, regulation of glucagon secretion, delaying gastric emptying, and decreasing food intake. Three Phase III comparative efficacy trials were identified that enrolled a total of 1,446 patients who received exenatide 5 pg SC BID, exenatide 10 mug SC BID, or placebo for 30 weeks in addition to their existing therapy with metformin, sulfonylurea, or both. In these trials, the addition of exenatide was associated with significant reductions in glycosylated hemoglobin (HbA(1c)) values (P < 0.001-P < 0.002), greater proportions of patients achieving an HbA(1c) 10% of patients receiving exenatide were hypoglycemia (19.6%), diarrhea (12.8%), and vomiting (12.8%). CONCLUSIONS: During clinical trials, exenatide added to existing metformin and/or sulfonylurea therapy in patients with T2DM reduced fasting and postprandial glucose concentrations, with improvements in HbA(1c) and modest weight loss. The main adverse effect associated with exenatide therapy was nausea.

Blood Glucose↗

PubMed2006

Intravenous proton pump inhibitors.

Intravenous (IV) administration of a proton pump inhibitor (PPI) is a faster way to achieve gastric acid suppression than oral administration of the same agent. Peak suppression after IV administration occurs within hours, compared with several days later after oral administration. Thus the IV route of administration offers a faster onset of gastric suppression, achievement of intragastric pH closer to neutrality, and better bioavailability. The PPIs that have IV formulations in the United States (esomeprazole, lansoprazole, and pantoprazole) are approved for different indications; the key differences among them relate to their ability to reach specific gastric pH, time to maintain a specific gastric pH, and ease of use of the IV formulation (eg, reconstitution, requirement of inline filters, infusion times).

2-Pyridinylmethylsulfinylbenzimidazoles↗

PubMed2006

MMX mesalamine.

Most current drug delivery systems in the treatment of ulcerative colitis and Crohn's disease release the active drug at the least effective location for treatment. The pharmaceutical industry has been developing different delivery systems for Multi-Matrix System (MMX) mesalamine for the treatment of Crohn's disease and ulcerative colitis. The new oral mesalamine formulation is a once-daily MMX tablet that delivers the mesalamine to the colon, making it most useful in the treatment of ulcerative colitis. The MMX coating matrix and coating system begin dissolution in the final portion of the ileum. This type of oral formulation may make MMX a preferred agent over other oral mesalamine and mesalamine-prodrug formulations that release the drug proximally in the gastrointestinal tract. Unlike previous formulations, it can be administered once daily for the treatment of ulcerative colitis.

Administration, Oral↗

PubMed2005

Phosphodiesterase 5 inhibitors for erectile dysfunction.

OBJECTIVE: To review the pharmacologic and clinical trial data of the Food and Drug Administration-approved phosphodiesterase 5 (PDE5) inhibitors for the treatment of erectile dysfunction (ED). DATA SOURCES: Primary research and review articles were identified through a search of ScienceDirect, PubMed/MEDLINE, and International Pharmaceutical Abstracts (1990-August 2004). The following search terms were used in the Medicine Dentistry and Pharmacology, Toxicology, and Pharmaceutical Sciences subcategories: phosphodiesterase 5 inhibitor, PDE5 inhibitor, erectile dysfunction, sildenafil, vardenafil, tadalafil, prostatectomy, and diabetes. Web of Science (1990-August 2004) was used to search for additional abstracts using the same search terms as above. The package inserts for sildenafil, vardenafil, and tadalafil were also consulted. STUDY SELECTION AND DATA EXTRACTION: All identified research, review articles, and abstracts were assessed for relevance, and all relevant information was included. Priority was given to the primary medical literature and clinical trial reports. DATA SYNTHESIS: ED is a common disorder in males with increased prevalence associated with age and presence of cardiovascular disease, prostatectomy, or diabetes mellitus. Sildenafil, vardenafil, and tadalafil are selective PDE5 inhibitors currently available for treatment of ED. Their pharmacology and pharmacokinetics vary slightly, but with potentially important clinical differences in duration of activity; all have similar clinical efficacy and adverse effect profiles in patients with ED of various causes. CONCLUSIONS: Sildenafil, vardenafil, and tadalafil are safe and effective PDE5 inhibitors for the treatment of ED.

3',5'-Cyclic-GMP Phosphodiesterases↗

PubMed2005

Rationale for using serotonergic agents to treat irritable bowel syndrome.

PURPOSE: The role of serotonin in gastrointestinal (GI)-tract functioning, the pharmacologic rationale for using serotonergic agents in the treatment of irritable bowel syndrome (IBS), and clinical experience with novel serotonergic agents are described. SUMMARY: IBS is a common multisymptom disorder that is associated with a high socioeconomic burden. The goal of treatment is to provide rapid and sustained global relief of the multiple symptoms of IBS with a single, effective, well-tolerated agent. Traditional treatment options target single symptoms, and many patients are dissatisfied with the level of relief achieved and adverse effects. Research has revealed that serotonin is involved in three major actions in the gut: (1) mediating intestinal motility, (2) mediating intestinal secretion in the GI tract, and (3) modulating perception in the bowels. Serotonin is also a vital link in the brain-gut axis. Alterations in key elements of serotonin signaling have been demonstrated in patients with IBS. Tegaserod, a selective serotonin type 4 (5-HT(4))-receptor partial agonist, is indicated for use in women with IBS whose primary bowel symptom is constipation. Alosetron, a 5-HT(3)-receptor antagonist, is indicated for use in women with severe diarrhea-predominant IBS in whom traditional therapies have failed. The clinical usefulness of several other serotonergic agents for IBS is being investigated. CONCLUSION: The use of serotonergic agents in patients with IBS is based on the critical role that serotonin plays in the maintenance of normal gut function and brain-gut communication. Pharmacologic therapies targeting specific serotonin receptors represent an important step in the management of IBS.

Animals↗

PubMed2005

Rifaximin: a nonabsorbed oral antibiotic.

Rifaximin is a rifamycin analogue with a broad spectrum of activity similar to that of rifampin; however, because it is poorly absorbed in the gastrointestinal tract, the focus of its development has been on intestinal infections and diseases. This agent has proven to be as effective as ciprofloxacin in treating travelers' diarrhea due to Escherichia coli, although it is ineffective in treating infections due to Campylobacter jejuni. Other potential uses for rifaximin in gastroenterologic disorders include treatment of hepatic encephalopathy, intestinal gas and gas-related symptoms, diverticular disease, intestinal bacterial overgrowth, pouchitis, ulcerative colitis, and active Crohn's disease. This article highlights several studies demonstrating the efficacy of rifaximin in treating travelers' diarrhea as well as other gastrointestinal diseases and discusses the drug's pharmacokinetics, indications, contraindications, warnings, precautions, adverse reactions, and dosing.

Anti-Infective Agents↗

PubMed2005

Adefovir dipivoxil: focus on its use in the treatment of chronic hepatitis B.

Adefovir is classified as a nucleotide reverse transcriptase inhibitor because it acts by inhibiting hepatitis B virus DNA polymerase (reverse transcriptase) and causing DNA chain termination after its incorporation into the viral DNA. Adefovir dipivoxil is indicated for the treatment of chronic hepatitis B in adults with evidence of active viral replication and either evidence of persistent elevations in serum aminotransferases (alanine [ALT] or aspartate [AST]) or histologically active disease. It is useful in the treatment of patients with either hepatitis B e antigen-positive or -negative chronic hepatitis B. The recommended adefovir dipivoxil dose in the treatment of chronic hepatitis B in patients with adequate renal function is 10 mg once daily. Adefovir dipivoxil therapy can reduce viral load, improve ALT, and produce histologic improvement in patients with chronic hepatitis B. Improvements are generally seen within the first few weeks of therapy and have shown persistence up to at least 3 years with continued therapy. Therapy with adefovir dipivoxil is generally well tolerated. However, nephrotoxicity is a risk with adefovir therapy, especially in patients receiving higher doses (30-120 mg/d). Patients should have their renal function monitored closely throughout therapy and may require an adjustment in dose relative to changes in the creatinine clearance. Lactic acidosis and severe hepatomegaly with steatosis may also occur during therapy.

Adenine↗

PubMed2005

Safety of balsalazide therapy in the treatment of inflammatory bowel disease.

Balsalazide is a mesalamine prodrug that is generally well tolerated and useful in the treatment of inflammatory bowel disease (IBD). This review will focus on newer safety information regarding the use of balsalazide in the treatment of patients with IBD. In general, mesalamine compounds such as balsalazide are better tolerated than sulfasalazine. Balsalazide therapy should be avoided in patients with known hypersensitivity reaction to salicylates, mesalamine, other balsalazide metabolites, or the components of the Colazal (Salix Pharmaceuticals; Morrisville, NC) capsule (silicon dioxide, magnesium stearate) but may be tolerated in patients who were unable to tolerate other mesalamine compounds for non-hypersensitivity reasons. Overall, balsalazide is well tolerated and effective in the treatment of IBD.

Aminosalicylic Acids↗

PubMed2004

Therapeutic equivalence of mesalamine products.

No bioequivalence studies have been conducted for mesalamine because of differences in formulation. Based on U.S. Food and Drug Administration definitions for bioequivalence, none of these drugs can be classified as bioequivalent or therapeutically equivalent. No adequate comparative trials have been conducted with equivalent mesalamine doses to determine if any of the current formulations are superior in the treatment of ulcerative colitis. All of these mesalamine formulations are effective, but they differ with regard to where the drug is released in the intestinal tract, which may influence the outcome in some patients. Therefore, the selection of a mesalamine agent should be based on the results of the clinical trials, individual patient response, compliance issues, and price, until comparative clinical trials are published.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed2004

The short- and long-term safety of 5-aminosalicylate products in the treatment of ulcerative colitis.

5-aminosalicylic acid agents are effective in the treatment of ulcerative colitis. Balsalazide, mesalamine, and olsalazine are alternative formulations to sulfasalazine for the delivery of 5-aminosalicylic acid. The newer compounds might be better tolerated than sulfasalazine in some patients, as long as the intolerance is not due to hypersensitivity to 5-aminosalicylic acid. Adverse events requiring the withdrawal of therapy seem to occur less frequently with balsalazide, mesalamine, and olsalazine compared with sulfasalazine. If patients are unable to tolerate any one of these three 5-aminosalicylic acid-releasing preparations, they might be able to tolerate one of the others, as long as the intolerance is not due to hypersensitivity to 5-aminosalicylic acid.

Adolescent↗

PubMed2004

Adalimumab: human recombinant immunoglobulin g1 anti-tumor necrosis factor monoclonal antibody.

Tumor necrosis factor (TNF) is a proinflammatory cytokine that is involved with normal inflammatory and immune responses and with the pathogenesis of chronic inflammatory medical conditions, such as rheumatoid arthritis, psoriatic arthritis, plaque psoriasis, and Crohn's disease. The newest therapies for these inflammatory conditions include the TNF biologic response modifiers infliximab, etanercept, and adalimumab. Adalimumab is a human recombinant immunoglobulin G1 anti-TNF monoclonal antibody. As monotherapy, or in combination with methotrexate or other traditional disease-modifying antirheumatic drugs, adalimumab can produce improvements in the signs and symptoms associated with rheumatoid arthritis and can slow progression of the joint destruction. The adverse effect profile of adalimumab seems to be comparable to that of etanercept. Adalimumab also seems to be useful in the treatment of psoriasis, psoriatic arthritis, and Crohn's disease; however, none of these indications are approved by the US Food and Drug Administration, and the optimal dosing regimen for these indications has not been established.

Adalimumab↗

PubMed2003

Oxaliplatin: a new drug for the treatment of metastatic carcinoma of the colon or rectum.

Oxaliplatin is a useful agent in combination with 5-fluorouracil/leucovorin for the treatment of patients with metastatic carcinoma of the colon or rectum whose disease has recurred or progressed during or within 6 months of completion of first-line therapy (a combination of bolus 5-fluorouracil/leucovorin and irinotecan). Oxaliplatin works by disrupting DNA replication and transcription and is cell-cycle nonspecific. In vitro, oxaliplatin has shown activity against numerous tumor lines, but it has only been approved for the treatment of metastatic carcinoma of the colon or rectum.

Antineoplastic Agents↗

PubMed2003

Pegylated interferon plus ribavirin for the treatment of chronic hepatitis C.

Peginterferon alfa-2a and peginterferon alfa-2b have been approved for the treatment of chronic hepatitis C virus (HCV) infection in adults who have compensated liver disease and have not been previously treated with interferon alfa. Peginterferon alfa-2a and peginterferon alfa-2b have also been approved for use in combination with ribavirin as therapy for these adults. Combining peginterferon alfa-2a or alfa-2b with ribavirin produces better activity against HCV than either drug alone. Interferon works by binding to specific receptors on the cell surface that initiate a complex cascade of protein-protein interactions leading to rapid activation of gene transcription. The effects of this interferon-stimulated gene modulation depend on the biologic system and may result in the inhibition of viral replication in infected cells, inhibition of cell proliferation, and immunomodulation. Pegylation of the interferon molecule increases its size; the absorption of the larger pegylated molecule is slower, its half-life is longer, and its rate of clearance from the plasma is lower than that of the native interferon. Thus, the pegylated molecule increases the duration of biologic activity. Factors that appear to influence the success of pegylated interferon therapy are HCV genotype, baseline viral load, presence of fibrosis or inflammation shown on the liver biopsy at baseline, and the patient's body weight or body surface area. Patients infected with HCV genotype 1 tend to have a lower response rate, require longer courses of therapy, and respond better when treated with a pegylated interferon plus ribavirin. Patients infected with HCV genotypes 2 or 3 have comparable responses when treated with interferon plus ribavirin or pegylated interferon plus ribavirin and can be treated with a lower dose of ribavirin and a shorter course of therapy (24 weeks vs 48 weeks for patients with genotype 1). Studies directly comparing peginterferon alfa-2a and peginterferon alfa-2b have not been performed.

Adult↗

PubMed2003

Pharmacogenomics of azathioprine and 6-mercaptopurine in gastroenterologic therapy.

The elimination of azathioprine and 6-mercaptopurine is greatly influenced by polymorphisms in the enzymes responsible for their metabolism. Patients who are deficient in thiopurine methyltransferase (TPMT) are at an increased risk for azathioprine- and 6-mercaptopurine-induced toxicities because of the accumulation of toxic metabolites, and patients with high TPMT activity may not receive maximum benefit because of the increased clearance. Therefore, routine TPMT genotyping prior to the initiation of azathioprine or 6-mercaptopurine therapy should be considered to decrease the risk of severe and possibly preventable adverse effects and to identify patients who might benefit from higher doses. However, measuring the TPMT activity at baseline is not a substitute for monitoring white blood cell counts throughout therapy because drug therapy and/or other conditions may still cause myelosuppression in these patients.

Azathioprine↗

PubMed2002

Insulin glargine: a new basal insulin.

OBJECTIVE: To review the pharmacology, pharmacokinetics, dosing guidelines, adverse effects, drug interactions, and clinical efficacy of insulin glargine. DATA SOURCES: Primary and review articles regarding insulin glargine were identified by MEDLINE search (1966-July 2001); abstracts were identified through Institute for Scientific Information Web of Science (1995-July 2001) and the American Diabetes Association. Additional information was obtained from the insulin glargine product information. STUDY SELECTION AND DATA EXTRACTION: All of the articles and meeting abstracts identified from the data sources were evaluated, and all information deemed relevant was included in this review. Priority was placed on data from the primary medical literature. DATA SYNTHESIS: Insulin glargine is a long-acting, recombinant human insulin analog that is given once daily as a basal source of insulin in patients with type 1 or type 2 diabetes mellitus. Modification of the basic insulin structure has produced a new insulin that is soluble at an acidic pH, but precipitates in the subcutaneous tissue and is slowly released from a depot. Insulin glargine has a slower onset of action than NPH insulin and a longer duration of action with no peak activity. Once-daily administration of insulin glargine has comparable efficacy to that of NPH insulin administered once or twice daily in basal-bolus regimens when used in combination with intermittent doses of regular insulin or insulin lispro in patients with type 1 and type 2 diabetes, and in conjunction with oral antidiabetic agents in patients with type 2 diabetes. Overall, insulin glargine has an incidence of hypoglycemia comparable to or less than that of NPH insulin, with a reduced incidence of nocturnal hypoglycemia compared with NPH insulin seen in some studies. CONCLUSIONS: Insulin glargine is a long-acting insulin analog capable of providing 24-hour basal insulin coverage when administered once daily at bedtime. Its activity profile, which lacks a pronounced peak, more closely resembles that of endogenous basal insulin than that of other intermediate- or long-acting insulins and appears more likely to be associated with a reduced incidence of hypoglycemia, particularly nocturnal hypoglycemia. Insulin glargine physiologically provides basal insulin but, for most patients, the addition of a rapid-acting insulin, like insulin lispro, before or with meals will need to be included in the treatment regimen to achieve optimal management of blood glucose concentrations.

Amino Acid Sequence↗

PubMed2002

Imatinib mesylate.

Imatinib is an example of a new group of drugs being developed using the principle of molecular targeting. Imatinib is able to kill the cancer cells and not the body's healthy cells. Imatinib mesylate is indicated for the treatment of patients with Kit (CD117)-positive unresectable and/or metastatic malignant gastrointestinal stromal tumors and patients with Philadelphia chromosome-positive chronic myeloid leukemia in blast crisis, accelerated phase, or in chronic phase after failure of interferon-alfa.

Animals↗

PubMed2002

Alendronate and risedronate: what you need to know about their upper gastrointestinal tract toxicity.

Adverse upper gastrointestinal (GI) tract events can occur with alendronate or risedronate therapy. Although the short-term, non-placebo-controlled comparisons of alendronate and risedronate indicated that risedronate therapy may be associated with a lower risk of upper GI toxicity than alendronate therapy, the placebo-controlled comparison shows no difference in the risk of upper GI toxicity between the two drugs. The risk of an adverse upper GI event increases when these drugs are used concurrently with nonsteroidal anti-inflammatory drug (NSAID) therapy, but this incidence is no more than that observed with concurrent placebo and NSAID therapy. Also, the risk of these adverse GI tract events can be decreased by following the dosing instructions (e.g., avoid lying down for 30 minutes after taking the drug and take the drug with a full glass of water) and may be decreased with once-weekly dosing.

Alendronate↗

PubMed2002

Esomeprazole: update and clinical review.

The U.S. Food and Drug Administration's Nonprescription Drugs Advisory Committee and Gastroenterological Drugs Advisory Committee recommended approval of omeprazole as an over-the-counter treatment of heartburn in patients who have at least two episodes of heartburn each week. The consumer studies that have been conducted indicate that the majority of patients understand the proposed labeling and could use the proposed label to determine if the omeprazole therapy was appropriate for them. Esomeprazole is an effective agent in the treatment of gastroesophageal reflux disease (GERD) and erosive esophagitis. Newer studies continue to support its efficacy and safety in the treatment of these conditions. Several of the most recent studies have included comparisons with other proton pump inhibitors. The results of these studies indicate that all the proton pump inhibitors are effective in treating GERD and erosive esophagitis and that some patients would benefit from esomeprazole therapy.

Anti-Ulcer Agents↗