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Biomedical subjects

Melanie S Joy

Publications and source records attributed to Melanie S Joy.

13 recordsLinked to original sources
PubMed2006

Lanthanum carbonate.

OBJECTIVE: To review the pharmacology, pharmacokinetics, clinical efficacy, and safety profile of lanthanum carbonate, a phosphate binder for chronic kidney disease (CKD). DATA SOURCES: Information was selected from PubMed (1965-October 2005). All studies presented as scientific posters and abstracts from nephrology meetings from 1999 to 2005 were also included. STUDY SELECTION AND DATA EXTRACTION: All published articles regarding lanthanum carbonate were included. In addition, abstracts and presentations from scientific meeting symposia were also considered for inclusion. DATA SYNTHESIS: Lanthanum carbonate has been recently approved as non-calcium-based therapy for phosphate reduction in patients with stage 5 CKD requiring dialysis. The recommended dose is 250-500 mg with meals, for a maximum of 1500 mg daily. Clinical studies have shown short- and long-term safety with lanthanum carbonate administration. Adverse effects were primarily gastrointestinal in nature. Clinical trials have also shown reductions in serum phosphorus to target concentrations, reductions in associated calcium-phosphorus product, and minimal effects on serum calcium and parathyroid hormone concentrations. CONCLUSIONS: Lanthanum carbonate is an effective phosphate-binding agent without significant risk of hypercalcemia or worsening metabolic acidosis. Lanthanum carbonate is a safe and effective drug for reduction of elevated serum phosphorus levels associated with stage 5 CKD. The role of lanthanum carbonate relative to other phosphate-binding drugs, such as calcium salts and sevelamer, remains to be determined.

Animals↗
PubMed2005

A pilot study using mycophenolate mofetil in relapsing or resistant ANCA small vessel vasculitis.

BACKGROUND: The treatment approaches to antineutrophil cytoplasmic autoantibody (ANCA) small vessel vasculitis expose patients to the risks associated with long-term use of corticosteroids and cytotoxic agents. In an effort to explore approaches to minimize risks, we conducted a pilot efficacy and safety study of mycophenolate mofetil (MMF) in the treatment of subjects with nonlife-threatening recurrent or cyclophosphamide-resistant ANCA-vasculitis. METHODS: MMF was initiated at 500 mg orally twice daily and gradually increased to a target dose of 1000 mg twice daily for a duration of 24 weeks. Concomitant therapy with corticosteroids was allowed. The Birmingham Vasculitis Activity Score (BVAS) was used to assess disease activity and treatment efficacy. ANCA titres, serum creatinine and adverse events were secondary measures of efficacy and/or toxicity. RESULTS: Twelve subjects were enrolled in the study. Treatment with MMF led to an improvement in disease activity as measured by the BVAS at 24 weeks (P = 0.0013) and 52 weeks (P = 0.0044) as compared to baseline. The BVAS decreased from an average of 9.1+/-3.5 at baseline (range, 3-17) to an average of 2.8+/-1.9 (range, 1-6) at 24 weeks and to 2.8+/-4.3 (range, 0-13) at 52 weeks. Early and sustained reductions in BVAS occurred in subjects initially classified as disease relapses vs those with treatment resistance. Side effect profile was consistent with the mechanism of action and pharmacokinetic disposition of MMF. CONCLUSIONS: MMF is a reasonable option in the treatment of non-life-threatening recurrent or resistant vasculitis and may obviate the immediate need for recurrent use of cytotoxic agents.

Administration, Oral↗
PubMed2005

A long-term, open-label extension study on the safety of treatment with lanthanum carbonate, a new phosphate binder, in patients receiving hemodialysis.

BACKGROUND: Lanthanum carbonate, a new phosphate binder, is effective in reducing serum phosphorus levels in patients with end-stage renal disease. A 1-year extension study to two randomized controlled studies was conducted to evaluate the long-term safety of lanthanum carbonate in patients who received hemodialysis. RESEARCH DESIGN AND METHODS: Patients from two previous lanthanum carbonate studies were eligible to continue treatment in a 1-year open-label extension. A total of 77 patients (N = 77; 11 from Study 1, 66 from Study 2) were enrolled in this extension. The mean age of patients was 60.9 years (SD +/- 12.5 years); 65% were male and 35% were female. All patients received lanthanum carbonate at the optimal dose for phosphorus control, determined in their previous study. Safety and tolerability were assessed by monitoring adverse events, laboratory parameters, and vital signs. The number of patients who maintained serum phosphorus levels at < or = 5.9 mg/dL (1.9 mmol/L) was recorded, along with serum calcium, calcium x phosphorus product, and parathyroid hormone levels. RESULTS: Lanthanum carbonate was well tolerated and was associated with few treatment-related adverse events. The most commonly reported adverse events were nausea (26.0%), peripheral edema (23.4%), and myalgia (20.8%). No treatment-related serious adverse events occurred. By Week 4, the mean serum phosphorus level had decreased by approximately 1 mg/dL to 5.7 +/- 2.0 mg/dL (1.84 +/- 0.7 mmol/L). At the end of the study, the mean pre-dialysis serum phosphorus level was 5.7 +/- 1.4 mg/dL (1.84 +/- 0.5 mmol/L); 53% of patients had controlled phosphorus levels. Calcium x phosphorus product decreased during Week 1 and remained within a clinically acceptable range thereafter. There were no clinically significant changes in serum calcium, or parathyroid hormone levels. CONCLUSION: Lanthanum carbonate is well tolerated and is effective for the long-term maintenance of serum phosphorus control in patients with end-stage renal disease.

Adolescent↗
PubMed2005

Calcineurin inhibitor-induced nephrotoxicity and renal expression of P-glycoprotein.

STUDY OBJECTIVE: To evaluate immunohistochemistry staining patterns for P-glycoprotein (P-gp) and a marker of early apoptosis (active caspase-3) in renal biopsy specimens obtained from solid organ transplant recipients with nephrotoxicity and those from a control group. DESIGN: Retrospective analysis of pathology specimens and medical records. SETTING: Medical university. SUBJECTS: Twenty-nine solid organ transplant recipients with nephrotoxicity and 32 control patients. MEASUREMENTS AND MAIN RESULTS: Medical records were reviewed for patient demographics, clinical laboratory results, and prescribed drugs. Immunohistochemistry techniques using primary antibodies to P-gp and active caspase-3 were performed to evaluate staining patterns of these proteins in the kidney specimens. Differences in measures of interest between groups were compared with the Fisher exact test for categoric data and Wilcoxon rank sum test for continuous data. Logistic and linear modeling were used to evaluate difference in measures of P-gp and active caspase-3 between groups while controlling for confounders. Immunohistochemistry confirmed the presence of P-gp in the renal tubules (apical and basal membranes and cytoplasm). Intensity of P-gp staining (score range 0-4) was reduced in renal specimens of transplant recipients with nephrotoxicity compared with the control specimens (mean +/- SD intensity scores 3.2 +/- 0.7 vs 3.8 +/- 0.4, p=0.0002). Neither P-gp-inducing nor P-gp-inhibiting drugs predicted expression of P-gp in the renal specimens of either group. The extent of tubular staining (score range 1-4) for the apoptosis marker, active caspase-3, was less in the nephrotoxicity group than in the control group (mean +/- SD extent scores 1.7 +/- 0.6 vs 2.8 +/- 0.5, p=0.0003). CONCLUSION: P-glycoprotein expression was less pronounced in renal biopsy specimens with calcineurin inhibitor-induced nephrotoxicity compared with the nonnephrotoxic control specimens. Reduced P-gp expression was evident even when the analysis controlled for factors such as renal function, age, sex, race, diabetes mellitus, level of proteinuria, or prescribed therapy with P-gp inducers or inhibitors. Interpretation of the results from active caspase-3 staining requires further study.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2005

Caring for patients with chronic kidney disease: a joint opinion of the ambulatory care and the nephrology practice and research networks of the American College of Clinical Pharmacy.

An increasing number of patients are developing chronic kidney disease (CKD). Appropriate care for patients with CKD must occur in the earliest stages, preferably before CKD progresses to more severe stages. Therefore, recognition and treatment of CKD and its associated complications must occur in primary care settings. Patients with CKD often have comorbid conditions such as diabetes mellitus, hypertension, and dyslipidemia, creating specific considerations when treating these diseases. Also, these patients have CKD-related conditions, including anemia and renal osteodystrophy, that are not traditionally evaluated and monitored by the primary care practitioner. Collectively, many opportunities exist for pharmacists who practice in the primary care setting to improve the care of patients with CKD.

Ambulatory Care↗
PubMed2005

Effects of atorvastatin on low-density lipoprotein cholesterol phenotype and C-reactive protein levels in patients undergoing long-term dialysis.

STUDY OBJECTIVES: To determine the effects of atorvastatin on low-density lipoprotein cholesterol (LDL) particle size and C-reactive protein (CRP) concentrations in patients undergoing long-term hemodialysis. Another objective was to compare the effects of atorvastatin on lipoprotein profiles as determined by direct versus indirect assessment of lipoprotein composition. DESIGN: Randomized, parallel-group substudy. SETTING: Two university-affiliated outpatient hemodialysis centers. PATIENTS: Nineteen patients with LDL levels above 100 mg/dl and with at least two cardiovascular risk factors. INTERVENTION: Patients were randomized in a 1:1 ratio to atorvastatin 10 mg/day or no treatment (control) for 20 weeks. MEASUREMENTS AND MAIN RESULTS: We compared the differences between LDL particle size and CRP levels at baseline and 20 weeks in the atorvastatin versus control groups. Baseline demographic characteristics were similar between the two groups. Atorvastatin therapy was associated with no change in mean LDL particle size (p=0.23) and with a 90% decrease in mean CRP level (p=0.52). When evaluated by standard chemical analysis, atorvastatin therapy reduced total cholesterol levels by 29% (p=0.025) and resulted in nonsignificant reductions in LDL, high-density lipoprotein cholesterol, and triglyceride levels. Treatment with atorvastatin was not associated with significant changes in lipoprotein profile as determined by nuclear magnetic resonance (NMR) spectroscopy. CONCLUSION: Treatment with atorvastatin did not affect LDL particle size but was associated with a sizable, yet nonsignificant, reduction in CRP concentrations. The drug had variable effects on lipoprotein concentrations as determined by chemical and NMR analytical methods. A larger study is necessary to provide definitive information on the effects of atorvastatin on LDL phenotype and CRP in patients with kidney disease.

Aged↗
PubMed2004

Calcimimetics and the treatment of primary and secondary hyperparathyroidism.

OBJECTIVE: To review the mechanism of action, development, and clinical application of the calcimimetic compounds being investigated for the treatment of primary and secondary hyperparathyroidism (HPT). DATA SOURCES: A MEDLINE search (1990-April 2004) was performed to identify all published articles related to calcimimetics. Published abstracts over the previous 5 years from various scientific meetings (American Society of Nephrology, American Society for Clinical Pharmacology and Therapeutics, American Society of Bone and Mineral Research) were also searched for reports regarding investigational calcimimetic agents. Data on cinacalcet HCl were provided by Amgen, Inc. STUDY SELECTION AND DATA EXTRACTION: Studies were selected based on number of patients included, relevance to the approved indications, and inclusion of pharmacokinetic and drug interaction information. DATA SYNTHESIS: The investigational calcimimetic compounds directly modulate the calcium-sensing receptor and can produce at least a 30% reduction in parathyroid hormone (PTH) secretion in secondary HPT. Cinacalcet appears to have more predictable pharmacokinetics and a lower risk of symptomatic hypocalcemia than the older agent, R-568. The safety profile and effective reduction in PTH and simultaneous reductions in calcium and phosphorus (and the calcium-phosphorus product) induced by cinacalcet make this agent advantageous over previously used therapies, such as vitamin D and phosphate-binding agents. More studies are required to determine additional uses of cinacalcet. CONCLUSIONS: Cinacalcet has a unique mechanism for reducing PTH concentration and appears to be a safe and effective oral therapy for both primary and secondary HPT.

Aniline Compounds↗
PubMed2003

Randomized, double-blind, placebo-controlled, dose-titration, phase III study assessing the efficacy and tolerability of lanthanum carbonate: a new phosphate binder for the treatment of hyperphosphatemia.

BACKGROUND: Lanthanum carbonate is a novel, non-calcium, non-aluminum phosphate binder under evaluation for the treatment of hyperphosphatemia in end-stage renal disease (ESRD) patients receiving either hemodialysis or continuous ambulatory peritoneal dialysis. METHODS: This 16-week study assessed the control of serum phosphorus with lanthanum carbonate, and its effects on serum calcium, calcium x phosphorus product, and parathyroid hormone (PTH). Hemodialysis patients > or =18 years old entered into a 1- to 3-week washout period during which serum phosphorus levels rose to >5.9 mg/dL (1.90 mmol/L). In total, 126 patients were titrated with lanthanum carbonate at doses containing 375, 750, 1,500, 2,250, or 3,000 mg/d elemental lanthanum, given in divided doses with meals over a 6-week period, to achieve serum levels < or =5.9 mg/dL. By the end of dose titration, 11/126 (9%) patients received < or =750 mg/d of lanthanum, 25 (20%) received 1,500 mg/d, 37 (29%) received 2,250 mg/d, and 53 (42%) received 3,000 mg/d. Following titration, patients were randomized to receive either lanthanum carbonate or placebo during a 4-week, double-blind maintenance phase. RESULTS: At the study endpoint, the mean difference in serum phosphorus between the lanthanum carbonate and placebo treatment arms was 1.91 mg/dL (0.62 mmol/L) (P < 0.0001). Calcium x phosphorus product (P < 0.0001) and serum PTH levels (P < 0.01) were also significantly lower with lanthanum carbonate versus placebo. The incidence of drug-related adverse events was similar between placebo- and lanthanum carbonate-treated patients. CONCLUSION: Lanthanum carbonate is an effective and well-tolerated agent for the treatment of hyperphosphatemia in patients with ESRD.

Aged↗
PubMed2003

Cinacalcet HCl: a calcimimetic agent for the management of primary and secondary hyperparathyroidism.

Cinacalcet HCl (AMG 073) is an investigational oral calcimimetic drug currently being evaluated for the treatment of primary and secondary hyperparathyroidism (HPT). Calcimimetics bind to the calcium-sensing receptors of the parathyroid glands and lower the sensitivity for receptor activation by extracellular calcium, thereby diminishing parathyroid hormone release. Cinacalcet HCl has demonstrated efficacy in controlling the hypercalcaemia of severe primary HPT and in reducing parathyroid hormone levels in patients with secondary HPT. Asymptomatic dose-dependent hypocalcaemia has occurred in some clinical trials. This drug has a favourable pharmacokinetic profile compared to its precursors and will prove useful as an additional/alternative agent in patients with primary and secondary HPT.

Cinacalcet↗
PubMed2002

Long-term glycemic control measurements in diabetic patients receiving hemodialysis.

Cardiovascular morbidity is increased in patients with diabetes mellitus and there is a great prevalence of diabetes and cardiovascular disease among patients with end-stage renal disease (ESRD). Control of glycemia can decrease cardiovascular and end-organ damage. Because the validity of glycemic control tests have not been rigorously studied in patients with ESRD, we evaluated the value of various measures in these patients. The overall clinical goal was to investigate whether hemoglobin A1C (A1C) accurately reflects actual glycemic control as compared with other measures in light of the importance of attaining appropriately controlled blood glucose (BG). The commonly used tests of total glycated hemoglobin (GHb) and A1C may be unreliable in patients with ESRD because of the presence of anemia, shortened red blood cell (RBC) survival, and assay interferences from uremia. The primary aim of this study was to assess the relationship of capillary BG measurements to A1C, GHb, total glycated plasma proteins (GPP), and fructosamine (Fr) in diabetic patients receiving hemodialysis. Twenty-three patients were instructed to obtain BG evaluations twice daily for 7 days by using the Elite glucometer (Bayer Corporation, Elkhart, IN). These determinations included 6 fasting, 6 preprandial, and 3 separate 2-hour postprandial levels. Blood was obtained on day 7 for measurement of A1C, GHb, GPP, and Fr. A1C was analyzed by an immunoassay, GPP and GHb were assayed by affinity high-performance liquid chromatography (HPLC), and Fr by automated nitroblue colorimetric assay. Scatter plots were generated by plotting the average BG versus A1C, GHb, GPP, or Fr. Linear regression was performed for each plot showing the following relationships: A1C = 0.0174 (BG) + 4.76 (r = 0.58; P < 0.05): GHb = 0.0371 (BG) + 3.57 (r = 0.584; P < 0.05): GPP = 0.0083 (BG) + 26.13 (r = 0.065; P = 0.77): Fr = 0.6865 (BG) + 250 (r = 0.345; P = 0.11). Despite anemia and shortened RBC lifespan in patients with ESRD, A1C in the range of 6% to 7% estimates glycemic control similarly to patients without severe renal impairment. A1C values above 7.5% may overestimate hyperglycemia in patients with ESRD. Thus, diabetic patients receiving hemodialysis may have long-term BG that are more properly controlled than previously determined, reducing their risks of the macro- and microvascular complications of diabetes mellitus.

Blood Glucose↗
PubMed2002

Cutaneous and systemic manifestations of drug-induced vasculitis.

OBJECTIVE: To evaluate the literature for published cases of drug-induced vasculitis with cutaneous and/or systemic manifestations. DATA SOURCES: The MEDLINE database was searched from 1965 to December 1999 for articles focusing on drugs and vasculitis, using various search terminologies (e.g., Churg-Strauss syndrome, Goodpasture's syndrome, Henoch-Schönlein purpura, various drugs suspected to induce vasculitis). Cases were included when they met the established criteria as described in the methodology. DATA SYNTHESIS: Drugs found to be most frequently associated with vasculitis were propylthiouracil, hydralazine, colony-stimulating factors, allopurinol, cefaclor, minocycline, D-penicillamine, phenytoin, isotretinoin, and methotrexate. The interval between the first exposure and appearance of symptoms was reported to be extremely variable (hours to years). Vasculitis has occurred after drug dosage increases and after rechallenge with the suspected drug. In the majority of cases, vasculitis has resolved after discontinuing the drug. Patients with more severe, often life-threatening, manifestations have required treatment with corticosteroids, plasmapheresis, hemodialysis, or cyclophosphamide. Death was the result in 10% of all published cases, with a predominance in patients in whom multiple organ systems were involved. CONCLUSIONS: Clinicians need to be suspect of drug-induced vasculitis to enable prompt diagnosis and treatment. This should improve patient outcomes based on the data referenced for this article.

Animals↗
PubMedDate not supplied

Darbepoetin alfa: a novel erythropoiesis-stimulating protein.

OBJECTIVE: To review the pharmacology, pharmacokinetics, clinical efficacy, and safety of darbepoetin alfa. DATA SOURCES: Pertinent references were identified by a MEDLINE search (1995-January 2001) of the medical literature, review of English-language literature and references of these articles, product information, and abstracts from professional meetings. STUDY SELECTION: Clinical efficacy data were gathered from all available trial data citing darbepoetin alfa. Additional information concerning pharmacology, pharmacokinetics, and safety was also reviewed. DATA SYNTHESIS: Darbepoetin alfa is a new erythropoiesis-stimulating protein with a threefold longer half-life than recombinant human erythropoietin (r-HuEPO). Darbepoetin alfa is approved for intravenous and subcutaneous administration in patients requiring and not requiring dialysis. Clinical studies in patients with chronic kidney disease (CKD) have shown darbepoetin alfa to be equivalent to r-HuEPO in terms of increases in hemoglobin concentration, percentage of patients obtaining target hemoglobin, and average time to reach target hemoglobin concentration. Trials are currently ongoing in patients receiving cancer chemotherapy. The adverse event profile appears to be similar between the 2 agents. CONCLUSIONS: The equivalent efficacy and safety profile, as well as the longer half-life, may make darbepoetin alfa an attractive alternative to r-HuEPO in patients with CKD. Since these patients need to receive r-HuEPO 1-3 times weekly at the expense of increased healthcare utilization to improve their hemoglobin, agents such as darbepoetin alfa, with longer durations of action, may reduce healthcare expenses. In addition, enhanced patient compliance may be realized with once-weekly or once every-other-week administration.

Adult↗