Publications (36)76.32 Total impact
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Article: Antihypertensive Efficacy of Hydrochlorothiazide Versus Chlorthalidone Combined With Azilsartan Medoxomil.
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ABSTRACT: BACKGROUND: Chlorthalidone has proven efficacy to reduce cardiovascular morbidity and mortality, yet it is infrequently used in practice. This study provides a direct comparison of chlorthalidone with hydrochlorothiazide, each combined with the angiotensin receptor blocker azilsartan medoxomil, on blood pressure reduction and control rates. METHODS: This is a randomized, double-blind, titrate-to-target blood pressure trial comparing the single-pill combination of azilsartan medoxomil and chlorthalidone versus co-administration of azilsartan medoxomil and hydrochlorothiazide in participants with stage 2 primary hypertension. After 2 weeks of treatment with azilsartan medoxomil 40 mg alone, all participants also received 12.5 mg of diuretic for 4 weeks (up to week 6) and were titrated to 25 mg for another 4 weeks (up to week 10) if they failed to achieve target blood pressure. The primary end point was change in clinic systolic blood pressure. Target blood pressure was defined as clinic blood pressure <140/90 mm Hg for participants without diabetes or chronic kidney disease or <130/80 mm Hg for participants with diabetes or chronic kidney disease. RESULTS: The mean age of the 609 participants was 56.4 years, and the mean baseline clinic blood pressure was 164.6/95.4 mm Hg. The primary end point analysis at week 6 demonstrated a greater reduction of clinic systolic blood pressure for the chlorthalidone (-35.1 mm Hg) versus hydrochlorothiazide combination (-29.5 mm Hg) (mean difference, -5.6 mm Hg; 95% confidence interval, -8.3 to -2.9; P <.001). The mean difference in 24-hour ambulatory systolic blood pressure at week 6 was -5.8 mm Hg (95% confidence interval, -8.4 to -3.2; P <.001), favoring the azilsartan medoxomil/chlorthalidone group. The percentage of participants achieving target clinic blood pressure at week 6 was greater for the chlorthalidone versus hydrochlorothiazide combination (64.1% vs 45.9%, P <.001). Drug discontinuations due to adverse events were not statistically significantly different between groups (9.3% vs 7.3%, P = .38), and hypokalemia was uncommon in both groups. CONCLUSIONS: Chlorthalidone combined with azilsartan medoxomil provides better blood pressure reduction and a higher likelihood of achieving blood pressure control than hydrochlorothiazide combined with azilsartan medoxomil. This benefit occurred without a difference in safety measurements.The American journal of medicine 08/2012; · 4.47 Impact Factor -
Article: Azilsartan medoxomil plus chlorthalidone reduces blood pressure more effectively than olmesartan plus hydrochlorothiazide in stage 2 systolic hypertension.
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ABSTRACT: Azilsartan medoxomil, an effective, long-acting angiotensin II receptor blocker, is a new treatment for hypertension that is also being developed in fixed-dose combinations with chlorthalidone, a potent, long-acting thiazide-like diuretic. We compared once-daily fixed-dose combinations of azilsartan medoxomil/chlorthalidone force titrated to a high dose of either 40/25 mg or 80/25 mg with a fixed-dose combination of the angiotensin II receptor blocker olmesartan medoxomil plus the thiazide diuretic hydrochlorothiazide force titrated to 40/25 mg. The design was a randomized, 3-arm, double-blind, 12-week study of 1071 participants with baseline clinic systolic blood pressure 160 to 190 mm Hg and diastolic blood pressure ≤119 mm Hg. Patients had a mean age of 57 years; 59% were men, 73% were white, and 22% were black. At baseline, mean clinic blood pressure was 165/96 mm Hg and 24-hour mean blood pressure was 150/88 mm Hg. Changes in clinic (primary end point) and ambulatory systolic blood pressures at week 12 were significantly greater in both azilsartan medoxomil/chlorthalidone arms than in the olmesartan/hydrochlorothiazide arm (P<0.001). Changes in clinic systolic blood pressure (mean±SE) were -42.5±0.8, -44.0±0.8, and -37.1±0.8 mm Hg, respectively. Changes in 24-hour ambulatory systolic blood pressure were -33.9±0.8, -36.3±0.8, and -27.5±0.8 mm Hg, respectively. Adverse events leading to permanent drug discontinuation occurred in 7.9%, 14.5%, and 7.1% of the groups given azilsartan medoxomil/chlorthalidone 40/25 mg, azilsartan medoxomil/chlorthalidone 80/25 mg, and olmesartan/hydrochlorothiazide 40/25 mg, respectively. This large, forced-titration study has demonstrated superior antihypertensive efficacy of azilsartan medoxomil/chlorthalidone fixed-dose combinations compared with the maximum approved dose of olmesartan/hydrochlorothiazide.Hypertension 06/2012; 60(2):310-8. · 6.21 Impact Factor -
Article: Blood pressure-lowering efficacy of the fixed-dose combination of azilsartan medoxomil and chlorthalidone: a factorial study.
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ABSTRACT: This study compared the efficacy and safety of fixed-dose combinations (FDCs) of the angiotensin II receptor blocker azilsartan medoxomil (AZL-M) and the thiazide-like diuretic chlorthalidone (CLD) with the individual monotherapies in a double-blind factorial study. A total of 1714 patients with clinic systolic blood pressure (SBP) 160 mm Hg to 190 mm Hg inclusive were randomized to AZL-M 0 mg, 20 mg, 40 mg, or 80 mg and/or chlorthalidone 0 mg, 12.5 mg, or 25 mg. The primary efficacy end point was change from baseline to 8 weeks in trough (hour 22-24) SBP by ambulatory blood pressure (BP) monitoring (ABPM). Patients' mean age was 57 years; 47% were men and 20% were black. Baseline trough BP was approximately 165/95 mm Hg and 151/91 mm Hg by clinic and ABPM measurements, respectively. For the pooled AZL-M/CLD 40/25-mg and 80/25-mg FDC groups, SBP reduction by ABPM at trough was 28.9 mm Hg and exceeded AZL-M 80 mg and CLD 25 mg monotherapies by 13.8 mm Hg and 13 mm Hg, respectively (P<.001 for both comparisons). Discontinuation rates and elevations in serum creatinine were dose-dependent and occurred more often in the AZL-M/CLD groups. In patients with stage 2 hypertension, treatment with the combination of AZL-M and CLD resulted in substantially greater SBP reduction compared with either agent alone.Journal of Clinical Hypertension 05/2012; 14(5):284-92. · 1.83 Impact Factor -
Article: Long-term safety and tolerability of the oral direct renin inhibitor aliskiren with optional add-on hydrochlorothiazide in patients with hypertension: a randomized, open-label, parallel-group, multicentre, dose-escalation study with an extension phase.
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ABSTRACT: Most patients with hypertension will require combination therapy with at least two agents from different antihypertensive classes to achieve blood pressure (BP) control. Thiazide diuretics, such as hydrochlorothiazide (HCTZ), are widely used in combination therapy. The volume reduction with these agents stimulates the renin-angiotensin system (RAS), making RAS inhibitors such as the direct renin inhibitor aliskiren a logical choice for combination therapy with HCTZ. The aim of this study was to investigate the long-term safety, tolerability and efficacy of the direct renin inhibitor aliskiren, with or without addition of the diuretic HCTZ. In the 12-month core study, patients with hypertension (mean sitting diastolic BP ≥90 mmHg and <110 mmHg) were randomized in a 3 : 2 ratio to once-daily aliskiren 150 mg or 300 mg. At months 2, 3, 4, 6 and 9, treatment was adjusted in patients not achieving a BP goal of <140/90 mmHg. Patients not at goal on aliskiren 150 mg once daily were up-titrated to aliskiren 300 mg once daily. Patients not at goal with aliskiren 300 mg once daily received add-on HCTZ 12.5 mg once daily, which was up-titrated to 25 mg once daily if BP remained inadequately controlled. At month 12, patients who received aliskiren/HCTZ 300 mg/25 mg once daily for at least 8 months in the core study were eligible to enter a 4-month extension study. Overall, 1625/1955 patients completed the core study, and 870/1955 patients received add-on HCTZ; 189/198 patients completed the 4-month extension. Aliskiren, with or without add-on HCTZ, was generally well tolerated; the incidence of adverse events (AEs) during the core study was similar among the four final treatment groups. The most frequently reported AEs in the core and extension studies were mild and transient cases of nasopharyngitis, headache and dizziness. Few patients exhibited laboratory abnormalities. Overall, aliskiren, with or without add-on HCTZ, reduced mean BP by 18.0/12.7 mmHg at core study endpoint, and 61.2% of patients achieved BP control. BP reductions with aliskiren/HCTZ 300 mg/25 mg combination therapy at the core study endpoint were maintained during the extension study. In patients with hypertension, long-term treatment with aliskiren, with or without add-on HCTZ, is well tolerated and provides effective BP lowering that is sustained over 12 months.Clinical Drug Investigation 12/2011; 31(12):825-37. · 1.82 Impact Factor -
Article: Sleep: yet to be mapped waters for blood pressure.
Hypertension 11/2011; 58(5):763-4. · 6.21 Impact Factor -
Article: Comparison of the novel angiotensin II receptor blocker azilsartan medoxomil vs valsartan by ambulatory blood pressure monitoring.
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ABSTRACT: Azilsartan medoxomil (AZL-M) is a unique angiotensin II receptor blocker (ARB) under development for the treatment of hypertension. To compare this ARB with another in the class, the authors studied the effects of AZL-M and valsartan (VAL) in 984 patients with primary hypertension in a randomized, double-blind, multicenter study using ambulatory and clinic blood pressure (BP) measurements. The primary end point was change from baseline in 24-hour mean ambulatory systolic BP following 24 weeks of treatment. Hierarchical analysis testing for noninferiority was followed by superiority testing of AZL-M (80 mg then 40 mg) vs VAL. The mean age of participants was 58 years, 52% were men, and 15% were black. Baseline 24-hour mean systolic BP was similar (approximately 145.6 mm Hg) in each group. AZL-M 40 mg and 80 mg lowered 24-hour mean systolic BP (-14.9 mm Hg and -15.3 mm Hg, respectively) more than VAL 320 mg (-11.3 mm Hg; P<.001 for 40-mg and 80-mg comparisons vs VAL). Clinic systolic BP reductions were consistent with the ambulatory results (-14.9 mm Hg for AZL-M 40 mg and -16.9 mm Hg for AZL-M 80 mg vs -11.6 mm Hg for VAL; P=.015 and P<.001, respectively). The reductions in 24-hour mean and clinic diastolic BPs were also greater with both doses of AZL-M than with VAL (P≤.001 for all comparisons). Small, reversible changes in serum creatinine occurred more often with AZL-M than with VAL; otherwise, safety and tolerability parameters were similar among the three groups. These data demonstrate that AZL-M across the effective dose range had superior efficacy to VAL at its maximal recommended dose without any meaningful increase in adverse events. These findings suggest that AZL-M could provide higher rates of hypertension control compared with other ARBs in the class.Journal of Clinical Hypertension 07/2011; 13(7):467-72. · 1.83 Impact Factor -
Article: Are there pleiotropic effects of antihypertensive medications or is it all about the blood pressure in the patient with diabetes and hypertension?
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ABSTRACT: Many small studies with varied surrogate end points and numerous preclinical data have suggested the likelihood of there being specific benefits that exceed simple blood pressure control with drug classes such as angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and calcium channel blockers, which may be particularly relevant to the patient with diabetes and hypertension. Large clinical trials, however, have provided only token support for this idea. Likewise, meta-analyses that have incorporated varied clinical trials, albeit with somewhat heterogeneous data, have not been particularly forthcoming in their support of this concept. In the patient with diabetes and hypertension, tight blood pressure control, more so than using a specific drug class, is the most important aspect of therapy.Journal of Clinical Hypertension 04/2011; 13(4):301-4. · 1.83 Impact Factor -
Article: Effects of the angiotensin receptor blocker azilsartan medoxomil versus olmesartan and valsartan on ambulatory and clinic blood pressure in patients with stages 1 and 2 hypertension.
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ABSTRACT: Azilsartan medoxomil is an angiotensin receptor blocker (ARB) being developed for hypertension treatment. To compare this ARB with others in the class, we studied the effects of 2 doses of azilsartan medoxomil, with valsartan 320 mg and olmesartan medoxomil (olmesartan) 40 mg, in a randomized, double-blind, placebo-controlled trial using ambulatory blood pressure (BP) monitoring and clinic BP measurements. The primary efficacy end point was the change from baseline in 24-hour mean systolic BP. Hierarchical analysis testing for superiority over placebo was followed by noninferiority analysis and then superiority testing of azilsartan medoxomil (80 mg and then 40 mg) versus the comparator ARBs. For 1291 randomized patients, mean age was 56 years, 54% were men, and baseline 24-hour mean systolic BP was 145 mm Hg. Azilsartan medoxomil at 80 mg had superior efficacy to both valsartan at 320 mg and olmesartan at 40 mg: placebo-adjusted 24-hour systolic BP was lowered (-14.3 mm Hg) more than 320 mg of valsartan (-10.0 mm Hg; P<0.001) and 40 mg of olmesartan (-11.7 mm Hg; P=0.009). Azilsartan medoxomil at 40 mg was noninferior to 40 mg of olmesartan (difference: -1.4 mm Hg [95% CI: -3.3 to 0.5]). For clinic systolic BP, both doses of azilsartan medoxomil were superior to the comparator ARBs. Safety and tolerability were similar among the placebo and 4 active treatments. These data demonstrate that azilsartan medoxomil at its maximal dose has superior efficacy to both olmesartan and valsartan at their maximal, approved doses without increasing adverse events. Azilsartan medoxomil could provide higher rates of hypertension control within the ARB class.Hypertension 03/2011; 57(3):413-20. · 6.21 Impact Factor -
Article: The comparative effects of azilsartan medoxomil and olmesartan on ambulatory and clinic blood pressure.
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ABSTRACT: The current study assesses the antihypertensive efficacy and safety of the investigational angiotensin receptor blocker (ARB), azilsartan medoxomil (AZL-M), compared with placebo and the ARB olmesartan medoxomil (OLM-M). This randomized, double-blind, placebo-controlled, multicenter study assessed change from baseline in mean 24-hour ambulatory systolic blood pressure (SBP) following 6 weeks of treatment. Patients with primary hypertension (n=1275) and baseline 24-hour mean ambulatory systolic pressure ≥ 130 mm Hg and ≤ 170 mm Hg were studied; 142 received placebo and the remainder received 20 mg, 40 mg, or 80 mg AZL-M or 40 mg OLM-M. Mean age of participants was 58 ± 11 years, baseline mean 24-hour SBP was 146 mm Hg. Dose-dependent reductions in 24-hour mean SBP at study end occurred in all AZL-M groups. Reduction in 24-hour mean SBP was greater with AZL-M 80 mg than OLM-M 40 mg by 2.1 mm Hg (95% confidence interval, -4.0 to -0.1; P=.038), while AZL-M 40 mg was noninferior to OLM-M 40 mg. The side effect profiles of both ARBs were similar to placebo. AZL-M is well tolerated and more efficacious at its maximal dose than the highest dose of OLM-M.Journal of Clinical Hypertension 02/2011; 13(2):81-8. · 1.83 Impact Factor -
Article: A simple and sensitive HPLC fluorescence method for determination of tadalafil in mouse plasma.
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ABSTRACT: A simple and sensitive high-performance liquid chromatographic (HPLC) method utilizing fluorescence detection was developed for the determination of the phosphodiesterase type 5 inhibitor tadalafil in mouse plasma. This method utilizes a simple sample preparation (protein precipitation) with high recovery of tadalafil (∼98%), which eliminates the need for an internal standard. For constituent separation, the method utilized a monolithic C(18) column and a flow rate of 1.0mL/min with a mobile phase gradient consisting of aqueous trifluoroacetic acid (0.1% TFA in deionized water pH 2.2, v/v) and acetonitrile. The method calibration was linear for tadalafil in mouse plasma from 100 to 2000ng/mL (r>0.999) with a detection limit of approximately 40ng/mL. Component fluorescence detection was achieved using an excitation wavelength of 275nm with monitoring of the emission wavelength at 335nm. The intra-day and inter-day precision (relative standard deviation, RSD) values for tadalafil in mouse plasma were less than 14%, and the accuracy (percent error) was within -14% of the nominal concentration. The method was utilized on mouse plasma samples from research evaluating the potential cardioprotective effects of tadalafil on mouse heart tissue exposed to doxorubicin, a chemotherapeutic drug with reported cardiotoxic effects.Journal of chromatography. B, Analytical technologies in the biomedical and life sciences 10/2010; 878(28):2891-5. · 2.78 Impact Factor -
Article: Natriuretic and neurohormonal responses to nesiritide, furosemide, and combined nesiritide and furosemide in patients with stable systolic dysfunction.
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ABSTRACT: In patients with heart failure, few data describe the neurohormonal response to nesiritide and furosemide either alone or in combination. This study systematically compared the effects of nesiritide, furosemide, and their combination on natriuresis/diuresis and plasma aldosterone in patients with chronic stable heart failure who were relatively diuretic resistant. Natriuretic, diuretic, and neurohormonal responses to furosemide and nesiritide will differ when these agents are administered alone vs. in combination. Twenty-eight subjects completed a multicenter, open-label, three-arm crossover study. Each subject received the following treatments in random order on alternate days: (1) furosemide, 40 mg intravenous bolus; (2) nesiritide, 2 microg/kg intravenous bolus followed by a 0.01 microg/kg/min infusion for 6 hours; (3) both furosemide and nesiritide, with furosemide given at least 15 minutes after initiation of nesiritide. Plasma aldosterone increased by 2.2 +/- 1.6 ng/dL after furosemide alone, decreased by 3.9 +/- 1.6 ng/dL after nesiritide alone (P = 0.005 vs furosemide alone and P = 0.56 vs furosemide plus nesiritide), and decreased by 2.8 +/- 1.6 ng/dL after furosemide plus nesiritide (P = 0.02 vs furosemide alone). Furosemide alone produced natriuresis/diuresis and a prompt rise in plasma aldosterone values. Nesiritide alone produced no significant natriuresis/diuresis, but decreased plasma aldosterone values. When furosemide was administered on a background of nesiritide infusion, the observed natriuresis/diuresis was similar to that seen with furosemide alone, without the anticipated increase in plasma aldosterone observed with furosemide alone.Clinical Cardiology 06/2010; 33(6):330-6. · 2.15 Impact Factor -
Article: A rapid and simple chemiluminescence method for screening levels of inosine and hypoxanthine in non-traumatic chest pain patients.
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ABSTRACT: A rapid and simple chemiluminescence method was developed for detection of inosine and hypoxanthine in human plasma. The method utilized a microplate luminometer with direct injectors to automatically dispense reagents during sample analysis. Enzymatic conversions of inosine to hypoxanthine, followed by hypoxanthine to xanthine to uric acid, generated superoxide anion radicals as a useful metabolic by-product. The free radicals react with Pholasin(®) , a sensitive photoprotein used for chemiluminescence detection, to produce measurable blue-green light. The use of Pholasin(®) and a chemiluminescence signal enhancer, Adjuvant-K™, eliminated the need for plasma clean-up steps prior to analysis. The method used 20 μL of heparinized plasma, with complete analysis of total hypoxanthine levels (inosine is metabolized to hypoxanthine using purine nucleoside phosphorylase) in approximately 3.7 min. The rapid chemiluminescence method demonstrated the capability of differentiating total hypoxanthine levels between healthy individuals, and patients presenting with non-traumatic chest pain and potential acute cardiac ischemia. The results support the potential use of chemiluminescence methodology as a diagnostic tool to rapidly screen for elevated levels of inosine and hypoxanthine in human plasma, potential biomarkers of acute cardiac ischemia.Luminescence 12/2009; 26(1):65-75. · 1.73 Impact Factor -
Article: Pamidronate-induced kidney injury in a patient with metastatic breast cancer.
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ABSTRACT: The American Society of Clinical Oncology recommends bisphosphonate use, such as intravenous pamidronate, for women with breast cancer who have radiographic evidence of bone destruction. However, pamidronate therapy has been associated with the development of the nephrotic syndrome. This renal abnormality has been posited to be due to a number of different mechanisms, including collapsing focal segmental glomerulosclerosis (FSGS). We present one such case of a patient who developed collapsing FSGS with nephrotic-range proteinuria after treatment with pamidronate for osteolytic bone metastases from an infiltrating ductal carcinoma of the breast. A possible mechanism of this kidney injury is mitochondrial apoptosis in podocytes and/or proximal tubular cells, which has been shown to occur in a dose-dependent fashion in experimental models. Renal prognosis is very poor if collapsing FSGS develops. Thus, prevention or early detection rather than effective therapy should be the primary consideration.The American Journal of the Medical Sciences 08/2009; 338(3):225-8. · 1.39 Impact Factor -
Article: Effect of omega-3-acid ethyl esters on the steady-state plasma pharmacokinetics of rosuvastatin in healthy adults.
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ABSTRACT: Patients with persistent hypertriglyceridemia while on statin therapy may require adjunctive lipid-lowering therapy to meet treatment goals. To assess the effect of concomitant administration of prescription omega-3-acid ethyl esters (P-OM3), triglyceride-lowering agents, on the steady-state pharmacokinetics of rosuvastatin. A randomized, open-label, repeated-dose, two-way crossover drug interaction study of two treatments - 4 g P-OM3 plus 40 mg rosuvastatin or 40 mg rosuvastatin alone administered daily for 14 days each under fasting conditions--was conducted in 48 non-smoking healthy adults. Main outcome measures: The primary determinants of drug interaction were the ln-transformed area under the plasma concentration versus time curve [AUC(t(ss))] over the final (day 14) 24 h dosing interval and maximum measured steady-state plasma rosuvastatin concentration [C(max(ss))] on day 14. Safety was assessed by clinical and laboratory testing and recording of adverse events. AUC(t(ss)) and C(max(ss)) following daily administration of rosuvastatin with P-OM3 were similar to those following monotherapy with rosuvastatin. All adverse events recorded during the study were classified as mild and self-limited. Administration of P-OM3 with rosuvastatin did not affect the pharmacokinetics of rosuvastatin under steady-state conditions in healthy individuals.Expert Opinion on Pharmacotherapy 01/2009; 9(17):2947-53. · 3.20 Impact Factor -
Article: Cardiac hypertrophy in neonatal nephrectomized rats: the role of the sympathetic nervous system.
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ABSTRACT: Cardiac hypertrophy is frequently encountered in patients with renal failure and represents an independent risk factor for cardiovascular morbidity and mortality. The pathogenesis of cardiac hypertrophy is related to multiple factors, including excess adrenergic activity. This study investigated how renal injury in the early stages of life affects the adrenergic system and thereby potentially influences cardiac growth. Biomarkers of cardiac hypertrophy were used to assess adrenergic function. Newborn male Sprague-Dawley rats were allocated to three groups of five rats each: 5/6 nephrectomy (Nx), pair-fed controls (PF), and sham-operated (SH). Nx animals had significantly higher plasma urea nitrogen, serum creatinine, and mean arterial blood pressure. The heart-weight/body-weight ratio of the Nx cohort was higher than SH and PF (p < 0.001) groups. Plasma norepinephrine (NE) of Nx animals was almost twofold higher than SH and PF (p < 0.01) animals. Compared with SH and PF, Nx animals had higher alpha1A-receptor protein expression, lower cardiac beta1- and beta2-receptor protein expression (p < 0.05), but higher G-protein-coupled receptor kinase-2 (GRK2) expression (p < 0.05). Norepinephrine transporter protein (NET) and renalase protein expression in cardiac tissue from Nx pups were significantly lower than SH and PF. Our data suggest that early age Nx animals have increased circulating catecholamines due to decreased NE metabolism. Enhancement of cardiac GRK2 and NE can contribute to cardiac hypertrophy seen in Nx animals. Furthermore, AKT (activated via alpha1A receptors), as well as increased alpha1A receptors and their agonist NE, might contribute to the observed hypertrophy.Pediatric Nephrology 10/2008; 24(2):367-77. · 2.52 Impact Factor -
Article: An HPLC method for determination of inosine and hypoxanthine in human plasma from healthy volunteers and patients presenting with potential acute cardiac ischemia.
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ABSTRACT: A simple and sensitive high-performance liquid chromatography (HPLC) method utilizing ultraviolet (UV) detection was developed for the determination of inosine and hypoxanthine in human plasma. For component separation, a monolithic C(18) column at a flow rate of 1.0 mL/min with an aqueous mobile phase of trifluoroacetic acid (0.1% TFA in deionized water pH 2.2, v/v) and methanol gradient was used. The method employed a one-step sample preparation utilizing centrifugal filtration with high component recoveries (approximately 98%) from plasma, which eliminated the need of an internal standard. The method demonstrated excellent linearity (0.25-5 microg/mL, R>0.9990) for both inosine and hypoxanthine with detection limits of 100 ng/mL. This simple and cost effective method was utilized to evaluate potential endogenous plasma biomarker(s), which may aid hospital emergency personnel in the early detection of acute cardiac ischemia in patients presenting with non-traumatic chest pain.Journal of Chromatography B 08/2007; 854(1-2):158-64. · 2.89 Impact Factor -
Article: Role of prescription omega-3 fatty acids in the treatment of hypertriglyceridemia.
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ABSTRACT: A prescription form of omega-3 fatty acids has been approved by the United States Food and Drug Administration as an adjunct to diet for the treatment of very high triglyceride levels. The active ingredients of omega-3 fatty acids are eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), which are responsible for the triglyceride lowering. The prescription product contains a total of 0.84 g of these two active ingredients in every 1-g capsule of omega-3 fatty acids. The total EPA and DHA dose recommended for triglyceride lowering is approximately 2-4 g/day. Fish oil products containing EPA and DHA are available without a prescription, but the American Heart Association advises that therapy with EPA and DHA to lower very high triglyceride levels should be used only under a physician's care. In patients with triglyceride levels above 500 mg/dl, approximately 4 g/day of EPA and DHA reduces triglyceride levels 45% and very low-density lipoprotein cholesterol levels by more than 50%. Low-density lipoprotein cholesterol levels may increase depending on the baseline triglyceride level, but the net effect of EPA and DHA therapy is a reduction in non-high-density lipoprotein cholesterol level. Alternatively, patients may receive one of the fibrates (gemfibrozil or fenofibrate) or niacin for triglyceride lowering if their triglyceride levels are higher than 500 mg/dl. In controlled trials, prescription omega-3 fatty acids were well tolerated, with a low rate of both adverse events and treatment-associated discontinuations. The availability of prescription omega-3 fatty acids, which ensures consistent quality and purity, should prove to be valuable for the medical management of hypertriglyceridemia.Pharmacotherapy 06/2007; 27(5):715-28. · 2.90 Impact Factor -
Article: Prescription omega-3 fatty acids for the treatment of hypertriglyceridemia.
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ABSTRACT: A review of the key properties and trial results associated with prescription omega-3 fatty acids (P-O3FA) and a description of its place in the treatment of hypertriglyceridemia and coronary heart disease (CHD) risk are presented. P-O3FA is made from the fish oil extracted from the fish carcass, which is put through a purification process that refines, esterifies, purifies, and concentrates the ethyl esters of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Each 1-g capsule provides 840 mg of EPA and DHA; the remaining 160 mg contains other omega-3 and omega-6 fatty acids, saturated fatty acids, and monounsaturated acids. When used at a daily dose of 4 g in patients with very high triglycerides (> or = 500 mg/dL), P-O3FA reduces triglycerides by an average of 45% and very-low-density-lipoprotein cholesterol by more than 50%. Changes in high-density-lipoprotein (HDL) cholesterol and non-HDL cholesterol are usually modest. P-O3FA has been tested in the GISSI-Prevenzione trial - a large, multicenter, open-label, randomized, controlled trial conducted in 11,324 patients. The results of the trial demonstrated significant reductions in all endpoints with the use of P-O3FA. P-O3FA has demonstrated an efficacy and safety in adult patients with high and very high triglycerides adjunct to diet, and the reduction in serum triglyceride levels was dependent on the baseline triglyceride levels. A large controlled clinical trial is necessary to determine if P-O3FA can be used to reduce CHD risk, either as combined with hydroxymethylglutaryl-coenzyme A reductase inhibitors or as monotherapy.American Journal of Health-System Pharmacy 03/2007; 64(6):595-605. · 1.96 Impact Factor -
Article: Pathologic basis and treatment considerations in chronic kidney disease-related hypertension.
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ABSTRACT: Chronic kidney disease (CKD) is both a cause and an effect of hypertension and is multifactorial in its origin. Beyond volume expansion, CKD-related hypertension is without defining characteristics of any consistency. Consequently, the order in which antihypertensive medications are given to the CKD patient with hypertension is arbitrary, although prescription practice is for the most part mindful of the need for multiple drug classes with at least one of them being a diuretic. It is not without reason that blood pressure goals in the hypertensive CKD patient are set at lower levels than those for patients with essential hypertension, but it remains to be determined how much the blood pressure should be decreased in the CKD patient.Seminars in Nephrology 08/2005; 25(4):246-51. · 2.12 Impact Factor -
Article: Liquid chromatography method for determination of bivalirudin in human plasma and urine using automated ortho-phthalaldehyde derivatization and fluorescence detection.
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ABSTRACT: A high-performance liquid chromatographic (HPLC) method was developed using solid-phase extraction, o-phthalaldehyde (OPA) derivatization and fluorescence detection for the determination of the direct thrombin inhibitor bivalirudin in human plasma and urine. The use of this assay will facilitate the study of the pharmacodynamics of bivalirudin in studies of special patient populations. A C(18) bioanalytical column at a flow rate of 1 ml/min with an aqueous trifluoroacetic acid (0.1% TFA in deionized water, pH 2.2, v/v) mobile phase and methanol gradient was used. The assay demonstrated linearity from 3 to 20 microg/ml bivalirudin in plasma, with a detection limit of 1 microg/ml. The method was utilized in a study evaluating the pharmacokinetic and pharmacodynamic effects of bivalirudin in patients undergoing percutaneous coronary interventions (PCIs).Journal of Chromatography B 05/2004; 802(2):355-9. · 2.89 Impact Factor
Top co-authors
Top Journals
Institutions
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2012
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The University of Chicago Medical Center
Chicago, IL, USA
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1997–2012
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Virginia Commonwealth University
- • Division of Nephrology
- • Division of Clinical Pharmacology and Hypertension
- • Department of Internal Medicine
Richmond, VA, USA
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2011
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UConn Health Center
Farmington, CT, USA
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