RESUMEN

Weed management is an important aspect of crop production, as weeds cause significant losses in terms of yield and quality. Various approaches to weed management are commonly practiced by crop growers. Due to limitations in other control methods, farmers often choose herbicides as a cost-effective, rapid and highly efficient weed control strategy. Although herbicides are highly effective on most weeds, they are not a complete solution for weed management because of the genetic diversity and evolving flexibility of weed communities. The excessive and indiscriminate use of herbicides and their dominance in weed control have triggered the rapid generation of herbicide-resistant weed species. Moreover, environmental losses of active ingredients in the herbicides cause serious damage to the environment and pose a serious threat to living organisms. Scientific advances have enabled nanotechnology to emerge as an innovation with real potential in modern agriculture, adding a new dimension in the preparation of controlled release formulations (CRF) of herbicides. Here the required amount of active ingredients is released over longer periods of time to obtain the desired biological efficacy whilst reducing the harmful effects of these chemicals. Various organic and inorganic carrier materials have been utilised in CRF and researchers have a wide range of options for the synthesis of eco-friendly carrier materials, especially those with less or no toxicity to living organisms. This manuscript addresses the history, progress, and consequences of herbicide application, and discusses potential ways to reduce eco-toxicity due to herbicide application, along with directions for future research areas using the benefits of nanotechnology.

RESUMEN

Injudicious application of available commercial herbicide formulations leads to water, air and soil contamination, which adversely affect the environment, ecosystems and living organisms. Controlled release formulation (CRFs) could be an effective way to reduce the problems associated with commercially available herbicides. Organo-montmorillonites are prominent carrier materials for synthesising CRFs of commercial herbicides. Quaternary amine and organosilane functionalised organo-montmorillonite and pristine montmorillonite were used to investigate their potential as suitable carriers for CRFs in herbicide delivery systems. The experiment involved a batch adsorption process with successive dilution method. Results revealed that pristine montmorillonite is not a suitable carrier for CRFs of 2,4-D due to its low adsorption capacity and hydrophilic nature. Conversely, octadecylamine (ODA) and ODA-aminopropyltriethoxysilane (APTES) functionalised montmorillonite has better adsorption capacities. Adsorption of 2,4-D onto both organoclays is higher at pH.3 (232.58% for MMT1 and 161.29% for MMT2) compared to higher pH until pH.7 (49.75% for MMT1 and 68.49% for MMT2). Integrated structural characterisation studies confirmed the presence of 2,4-D on the layered organoclays. The Freundlich adsorption isotherm model fitted best to the experimental data, which revealed an energetically heterogeneous surface of the experimental organoclays, and adsorption which specifically involved chemisorption. The cumulative desorption percentages of adsorbed 2,4-D from MMT1(2,4-D loaded) and MMT2(2,4-D loaded) after seven desorption cycles were 65.53% and 51.45%, respectively. This outcome indicates: firstly, both organoclays are potential carrier materials for CRFs of 2,4-D; secondly, they have the ability to reduce the instantaneous release of 2,4-D immediately after application; and thirdly, eco-toxicity is greatly diminished.

Asunto(s)

Herbicidas , Herbicidas/química , Bentonita/química , Silicatos de Aluminio/química , Preparaciones de Acción Retardada , Ecosistema , Arcilla , Adsorción , Ácido 2,4-Diclorofenoxiacético

RESUMEN

The aim of this study was to evaluate the bioequivalence of generic nifedipine controlled-release tablet compared to branded product under fasting and fed conditions. A randomized, single-dose, 2-period, crossover study with a 7-day washout period was performed in 84 healthy Chinese volunteers (fasting cohort, n = 42; fed cohort, n = 42). In each study period, volunteers were assigned to receive a single oral dose of the generic or reference product (30 mg). Blood samples were collected before dosing and up to 72 hours after administration. The plasma concentration of nifedipine was determined by a validated liquid chromatography-tandem mass spectrometry method. Pharmacokinetic parameters were obtained using a noncompartmental model and log-transformed pharmacokinetic parameters (maximum plasma concentration, area under the plasma concentration-time curve (AUC) from time 0 to the last measurable concentration, AUC from time 0 to infinity) were used to evaluate bioequivalence. The results showed that the 90% confidence interval for the geometric mean ratio of pharmacokinetic parameters of the test and reference products ranged from 80.0% to 125.0% in both the fasting and fed cohorts, meeting the criteria for bioequivalence. No serious adverse events were reported throughout the study and no adverse events led to withdrawal from the study. Food effects were found in both the test and reference products, with mean maximum plasma concentration, AUC from time 0 to the last measurable concentration, and AUC from time 0 to infinity increased by 23.7%, 20.7%, and 20.5%, respectively, for the test product and 35.2%, 13.4%, and 14.7% for the reference product after a high-fat and high-calorie breakfast.

Asunto(s)

Pueblos del Este de Asia , Nifedipino , Humanos , Área Bajo la Curva , Estudios Cruzados , Preparaciones de Acción Retardada/efectos adversos , Preparaciones de Acción Retardada/farmacocinética , Preparaciones de Acción Retardada/uso terapéutico , Ayuno , Nifedipino/efectos adversos , Nifedipino/sangre , Nifedipino/farmacocinética , Nifedipino/uso terapéutico , Comprimidos , Equivalencia Terapéutica , Voluntarios Sanos

RESUMEN

Local cancer treatment by in situ injections of thermo-responsive hydrogels (HG) offers several advantages over conventional systemic anti-cancer treatments. In this work, a biodegradable and multicompartmental HG composed of N-isopropylacrylamide, cellulose, citric acid, and ceric ammonium nitrate was developed for the controlled release of hydrophilic (doxorubicin) and hydrophobic (niclosamide) drugs. The formulation presented ideal properties regarding thermo-responsiveness, rheological behavior, drug release profile, biocompatibility, and biological activity in colon and ovarian cancer cells. Cellulose was found to retard drugs release rate, being only 4 % of doxorubicin and 30 % of niclosamide released after 1 week. This low release was sufficient to cause cell death in both cell lines. Moreover, HG demonstrated a proper injectability, in situ prevalence, and safety profile in vivo. Overall, the HG properties, together with its natural and eco-friendly composition, create a safe and efficient platform for the local treatment of non-resectable tumors or tumors requiring pre-surgical adjuvant therapy.

Asunto(s)

Hidrogeles , Neoplasias , Acrilamidas , Celulosa/farmacología , Doxorrubicina/química , Doxorrubicina/farmacología , Humanos , Hidrogeles/química , Niclosamida , Temperatura

RESUMEN

The physiological changes following Roux-en-Y gastric bypass (RYGB) surgery may impact drug release from mechanistically different controlled-release tablets, making generic substitution inappropriate. This study aimed to characterise the pharmacokinetic-pharmacodynamic relationships of oxycodone from a lipid-based and water-swellable controlled-release tablet in RYGB patients. Twenty RYGB patients received 10-mg oral solution oxycodone or 20-mg controlled-release (water-swellable or lipid-based) oxycodone in a three-way, randomised, semiblinded and cross-over study. Blood sampling and pupillary recordings were conducted over a 24-h period. A previously established pharmacokinetic-pharmacodynamic model of these three formulations in healthy volunteers was used in the analysis as a reference model. No differences in absorption kinetics were seen between controlled-release formulations in patients. However, the absorption lag time was 11.5 min in patients vs 14 min in healthy volunteers for controlled-release tablets (P < 0.001). Furthermore, oral bioavailability was 14.4% higher in patients compared to healthy volunteers regardless of formulation type (P < 0.001). Oxycodone pharmacodynamics were not significantly affected by formulation or patient status. However, baseline pupil diameter was inversely correlated with age (P < 0.001) and plasma concentrations of oxycodone at half-maximum effect were 31% lower in males compared to females (P < 0.05). Generic substitution of monophasic lipid-based and water-swellable controlled-release oxycodone tablets may be considered safe in RYGB patients.

Asunto(s)

Preparaciones de Acción Retardada/farmacología , Preparaciones de Acción Retardada/farmacocinética , Derivación Gástrica/efectos adversos , Oxicodona/farmacología , Oxicodona/farmacocinética , Administración Oral , Adulto , Anciano , Anciano de 80 o más Años , Analgésicos Opioides/farmacocinética , Analgésicos Opioides/farmacología , Estudios Cruzados , Femenino , Humanos , Masculino , Persona de Mediana Edad , Distribución Aleatoria

RESUMEN

Oral controlled-release formulations are playing an ever-increasing role in opioid therapy; however, little is known about their influence on the relationship between pharmacokinetics and pharmacodynamics. The study aim was to characterize the pharmacokinetic-pharmacodynamics of two controlled-release tablet formulations and a liquid formulation of oxycodone in healthy, opioid-naïve volunteers, which can serve as a reference for future patient studies. A semi-double-blinded, three-way crossover study was conducted, with fifteen healthy volunteers receiving two differently designed 20 mg monophasic controlled-release oxycodone tablets and 10 mg oral solution oxycodone in a randomized order. Venous plasma concentrations and pupil diameter were determined pre-dose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.33, 2.66, 3, 3.33, 3.66, 4, 5, 6, 8, 12 and 24 hour post-dose. Oxycodone pharmacokinetics was best described by a two-compartment model with first-order absorption. The controlled-release formulations had an absorption lag of 0.23 hour and a slower absorption rate constant (kaCR  = 0.19 hour-1 ) compared to the oral solution (kaSOL  = 0.94 hour-1 ). Effects on pupil diameter were delayed relative to plasma (14 minutes half-life) for all formulations and were best described by a proportional Emax model. The plasma concentration of oxycodone at half-maximum effect was lower in males (31.1 µg/L) compared to females (52.8 µg/L; P < .001). The absorption profile of controlled-release oxycodone formulations provided a prolonged onset and offset of action compared to oral solution oxycodone. The controlled-release formulations showed no differences in pharmacokinetic and pharmacodynamic parameters suggesting that both may be used interchangeably in human beings with normal gastrointestinal function.

Asunto(s)

Analgésicos Opioides/administración & dosificación , Modelos Biológicos , Oxicodona/administración & dosificación , Administración Oral , Adulto , Analgésicos Opioides/farmacocinética , Analgésicos Opioides/farmacología , Estudios Cruzados , Preparaciones de Acción Retardada , Método Doble Ciego , Femenino , Semivida , Humanos , Masculino , Persona de Mediana Edad , Oxicodona/farmacocinética , Oxicodona/farmacología

RESUMEN

After 32 years as a researcher in a pharmaceutical company, the author has served as a professor in the Development of Pharmaceutical Engineering and Drug Delivery Science at University of Shizuoka for the past 11 years. The research I was involved in can be categorized into four main items. First, the crystal transformation of clarithromycin (CAM) was focused on to develop the CAM high-loaded sustained release and gastro-floating formulations. Furthermore, the stabilization mechanism of CAM in the gastro-intestinal tract was clarified to elucidate gel formation under conditions of low pH. Second, the development of novel dosage regimens and optimization of formulation design were carried out using powder technology. In this category, a wax matrix formulation for taste masking, highly drug-loaded fine globular granules using a multi-functional rotor processor, and orally disintegrating tablets treated with microwave or high-pressure carbon dioxide were our targets. The third category was the manufacture of dispersion systems including lipid nanoparticles and cubosomes in order to improve the bioavailability and stability of poorly water-soluble drugs. The fourth category was the development and application of novel physical testing methods including investigation of the internal structure of fine granules using microtomography with synchrotron X-ray radiation, dissolution of spherical granules under non-sink conditions, mathematical models to analyze the dissolution behavior of metastable crystals or amorphous drugs and prediction of the available surface area of tablets during dissolution process.

Asunto(s)

Antibacterianos/química , Antibacterianos/farmacocinética , Claritromicina/química , Claritromicina/farmacocinética , Composición de Medicamentos/métodos , Diseño de Fármacos , Tecnología Farmacéutica , Animales , Disponibilidad Biológica , Cristalización , Liberación de Fármacos , Estabilidad de Medicamentos , Concentración de Iones de Hidrógeno , Lípidos , Nanopartículas , Nanotecnología , Ratas , Solubilidad , Comprimidos , Agua , Difracción de Rayos X

RESUMEN

Malaria is a major public health problem with hundreds of thousands of deaths yearly. Extracts of Peschiera fuchsiaefolia (Pf), an Apocynaceae family plant, are used as malaria treatment by several populations. Artemisinin is another effective largely used antimalarial agent but susceptible to generate resistant forms of Plasmodium. To reduce the risk of new resistant strains' appearance, the WHO recommended artemisinin-based combination therapy (ACT) with another bioactive agent, ensuring a long duration of antiplasmodial activity. Pf alkaloids are good candidates for ACT, but their solubility is very low. This research was aimed to improve the solubility of Pf alkaloids by complexation via their amine groups with carboxylate groups of carboxymethylstarch (CMS), an excipient used to formulate oral dosage forms for controlled drug release. It was found that when complexed as CMS-Pf, the solubility of Pf is increased (four to five times in function of dissolution medium). A new specific and faster approach to evaluate the solubility was proposed, measuring the effective saturation concentration of the compound of interest via one of its specific capacities, i.e., absorption capacity at a specific wavelength or antioxidant properties. This approach is more convenient for solubility evaluation of various active agents from complexes or crude extracts, or in heterogeneous samples. Also, the storage stability was markedly improved from 1 week for Pf co-processed with maltodextrin (MD/Pf) to several months for CMS-Pf (in similar controlled temperature and humidity conditions). The co-processing as MD/Pf or complexation as CMS-Pf affected physical properties but not the biological (i.e., antioxidant) activity of Pf.

Asunto(s)

Alcaloides/química , Antimaláricos/administración & dosificación , Apocynaceae/química , Ácidos Carboxílicos/química , Preparaciones de Acción Retardada , Extractos Vegetales/uso terapéutico , Antimaláricos/uso terapéutico , Excipientes , Humanos , Malaria/tratamiento farmacológico , Solubilidad

RESUMEN

PURPOSE: Pregabalin is a widely used drug for the management of neuropathic pain. This study compared the pharmacokinetics of the GLA5PR GLARS-NF1 tablet, a 150-mg controlled-release formulation of pregabalin taken once daily, with those of a 75-mg immediate-release (IR) capsule formulation of pregabalin taken twice daily with a 12-h interval between doses. METHODS: Two separate studies, single dose and multiple dose, were conducted with a sequence-randomized, open-label crossover design. In the single-dose study, 30 participants each received 3 treatments: two 75-mg IR capsules taken 12 h apart, each after a high-fat meal (SRF treatment); a single 150-mg GLA5PR GLARS-NF1 tablet taken after a high-fat meal (STF treatment); and a single 150-mg GLAR5PR GLARS-NF1 tablet taken in an overnight-fasted state (ST treatment). In the multiple-dose study, 24 participants each received 2 treatments, both of which occurred over 3 days: one 75-mg IR capsule in the evening after a standardized meal and a second 75-mg IR capsule the following morning after a standardized meal, for 3 days (MRF treatment); and a single 150-mg GLA5PR GLARS-NF1 tablet in the evening after a standardized meal, for 3 days (MTF treatment). Blood samples for pharmacokinetic assessments were collected over the 36 h following drug administration in each treatment period. FINDINGS: In the single-dose study, the geometric mean ratios (GMRs) of the Cmax and the AUClast values of the GLA5PR GLARS-NF1 tablet to those of the IR capsules (STF/SRF) were 1.047 (90% CI, 0.971-1.129) and 0.757 (90% CI, 0.694-0.826), respectively. In the multiple-dose study, the GMRs (MTF/MRF) of the Cmax and the AUC values over the dosing interval were 1.277 (90% CI, 1.210-1.348) and 0.974 (90% CI, 0.933-1.017), respectively. The systemic pregabalin exposure from the GLA5PR GLARS-NF1 tablet was higher in the fed state than in the fasted state; GMRs (STF/ST): Cmax, 1.458 (90% CI, 1.353-1.573) and AUClast, 1.655 (90% CI, 1.518-1.804). IMPLICATIONS: The overall pregabalin exposure after multiple administrations of GLA5PR GLARS-NF1 tablets was comparable to that after multiple administrations of the IR capsules. A single administration of the GLA5PR GLARS-NF1 tablet produced lower overall pregabalin exposure than that of the same dose administered in 2 IR capsules taken every 12 h. A high-fat diet significantly increased the bioavailability of the GLA5PR GLARS-NF1 tablet. ClinicalTrials.gov identifiers: NCT01638273 and NCT02326987.

Asunto(s)

Analgésicos/farmacocinética , Pregabalina/farmacocinética , Adulto , Área Bajo la Curva , Disponibilidad Biológica , Cápsulas , Estudios Cruzados , Preparaciones de Acción Retardada/farmacocinética , Ayuno , Voluntarios Sanos , Humanos , Masculino , Comprimidos , Adulto Joven

RESUMEN

α-Amylase-responsive carrier for controlled release of avermectin (AVM) was prepared based on α-cyclodextrin (α-CD) anchored hollow mesoporous silica (HMS) using α-CD as a capping molecule. The release of AVM was studied at different temperatures, pH values and in the presence or absence of α-amylase. The results revealed that the AVM-encapsulated controlled release formulation (AVM-CRF) has a drastic enzymatic dependence, an excellent encapsulation efficacy reaching 38%, and outstanding UV and thermal shielding ability. The AVM-CRF biological activity survey shows excellent toxicological properties against Plutella xylostella larvae, which confirms that α-CD caps could be uncapped enzymatically in vivo and release AVM, inducing P. xylostella larval death. AVM-CRF has a notable capability to keep 0.6 mg L-1 AVM biologically active until 14th day with 83.33% mortality of the target insect, which was 40% higher than that of treated with AVM commercial formulation. The study provides a theoretical basis for the application of pesticide reduction.

Asunto(s)

Portadores de Fármacos/administración & dosificación , Insecticidas/administración & dosificación , Ivermectina/análogos & derivados , Dióxido de Silicio/administración & dosificación , alfa-Amilasas/metabolismo , alfa-Ciclodextrinas/administración & dosificación , Animales , Ivermectina/administración & dosificación , Larva/efectos de los fármacos , Lepidópteros/efectos de los fármacos , Porosidad

RESUMEN

This study focuses on evaluating the potential of transferring from a batch process to continuous process for manufacturing of the extended release formulation. Metformin hydrochloride (HCl) was used in the model formulation which was intended to contain the high amount of hydrophilic drug. The effects of barrel temperature, binder type, powder feed rate, and screw speed on granule properties (size and strength) and torque value in twin screw granulation were investigated. Due to the high content of hydrophilic model drug, the granules prepared at a higher temperature with HPMC binding solution had the narrower size distribution and greater strength than the granules prepared with distilled water as a binding solution. After continuous drying and milling steps, the granules (continuous process) satisfied the fundamental purpose of granulation with size and flowability, despite different shape compared with the granules (batch process). Furthermore, there were no significant differences between two granulation processes in tablet properties, such as tablet hardness and in vitro release. The considerations and strategies used in this study to transfer from a batch to continuous process can be applied to other existing formulations based on high shear granulation to enable rapid process transfer in the pharmaceutical industry.

Asunto(s)

Composición de Medicamentos , Metformina/administración & dosificación , Química Farmacéutica , Preparaciones de Acción Retardada/química , Tamaño de la Partícula , Comprimidos

RESUMEN

Efficacy of spinosad and malathion loaded in eco-friendly biodegradable formulations was evaluated for controlling Culex pipiens larvae. Malathion (organophosphorus larvicide) and spinosad (naturally derived insecticide) were loaded on chitosan/alginate/gelatin capsules. Capsules were characterized by size measurement, scanning electron microscopy, Fourier transform infrared spectroscopy, and water uptake. In vitro release kinetics of the larvicides was studied in the running and stagnant water. Biochemical studies on the larvae treated with technical and formulated insecticides were also demonstrated. The results indicated that the released spinosad was active for a long time up to 48 and 211 days in the running and stagnant water, respectively. However, the capsules loaded with malathion showed larvicidal activity for 20 and 27 days in the running and stagnant water, respectively. Technical and formulated malathion and spinosad had an inhibition effect on acetylcholinesterase, carboxylesterase, and glutathione S-transferase. The results proved that the prepared capsules consisting of biodegradable polymers containing larvicides could be effective as controlled-release formulation against C. pipiens larvae for a long period.

RESUMEN

INTRODUCTION: Melatonin is a neurohormone involved in the regulation of circadian rhythms, with potent antioxidant activity. It has a wide functional repertoire, with effects almost on all tissues and organs. It is mainly used as a dietary supplement for sleep regulation and re-synchronization of disrupted circadian rhythms. Melatonin has very low toxicity, but some pharmacokinetic issues, such as limited oral bioavailability and short half-life, limit its tissue availability. AREAS COVERED: Patents and patent applications from 2012 to September 2014 in which melatonin or synthetic analogues are claimed for the prevention or treatment of pathological conditions. EXPERT OPINION: Melatonin is considered a valuable substance that can be safely administered for the prevention and treatment of many diverse diseases. A major trend in 2012 - 2014 patents is the co-administration of melatonin with other drugs to increase the efficacy of the treatment and reduce side-effects. Two different actions have been combined in hybrid ligands (e.g., melatonin-tamoxifen and melatonin-tacrine derivatives). Further experimental evidence is needed to support the usefulness of these approaches. The number of new melatonin analogues has shown a marked decrease in the past 3 years, with claimed applications mainly as hypnotic or antioxidant agents.

Asunto(s)

Antioxidantes/uso terapéutico , Ritmo Circadiano/fisiología , Melatonina/uso terapéutico , Animales , Antioxidantes/farmacocinética , Disponibilidad Biológica , Suplementos Dietéticos , Semivida , Humanos , Hipnóticos y Sedantes/farmacocinética , Hipnóticos y Sedantes/uso terapéutico , Ligandos , Melatonina/metabolismo , Melatonina/farmacocinética , Patentes como Asunto , Distribución Tisular

RESUMEN

Developing new antiretroviral therapies for HIV-1 infection with potential for less frequent dosing represents an important goal within drug discovery. Herein, we present the discovery of ethyl (1-((4-((4-fluorobenzyl)carbamoyl)-1-methyl-2-(2-(5-methyl- 1,3,4-oxadiazole-2-carboxamido)propan-2-yl)-6-oxo-1,6-dihydropyrimidin-5-yl)oxy)ethyl) carbonate (MK-8970), a highly optimized prodrug of raltegravir (Isentress). Raltegravir is a small molecule HIV integrase strand-transfer inhibitor approved for the treatment of HIV infection with twice-daily administration. Two classes of prodrugs were designed to have enhanced colonic absorption, and derivatives were evaluated in pharmacokinetic studies, both in vitro and in vivo in different species, ultimately leading to the identification of MK-8970 as a suitable candidate for development as an HIV therapeutic with the potential to require less frequent administration while maintaining the favorable efficacy, tolerability, and minimal drug-drug interaction profile of raltegravir.

Asunto(s)

Inhibidores de Integrasa VIH/química , Oxadiazoles/química , Profármacos/química , Pirimidinonas/química , Pirrolidinonas/química , Acetales/química , Animales , Área Bajo la Curva , Carbonatos/química , Perros , Evaluación Preclínica de Medicamentos , Integrasa de VIH/química , Integrasa de VIH/metabolismo , Inhibidores de Integrasa VIH/síntesis química , Inhibidores de Integrasa VIH/farmacocinética , VIH-1/enzimología , Semivida , Hepatocitos/metabolismo , Humanos , Mucosa Intestinal/metabolismo , Masculino , Oxadiazoles/síntesis química , Oxadiazoles/farmacocinética , Profármacos/síntesis química , Profármacos/farmacocinética , Pirimidinonas/síntesis química , Pirimidinonas/farmacocinética , Curva ROC , Raltegravir Potásico , Ratas , Ratas Wistar , Relación Estructura-Actividad

RESUMEN

Degradation kinetics of microencapsulated chlorpyrifos (CPF-MC) in soil and its influence on soil microbial community structures were investigated by comparing with emulsifiable concentration of chlorpyrifos (CPF-EC) in laboratory. The residual periods of CPF-MC with fortification levels of 5 and 20mg/kg reached 120 days in soil, both of the degradation curves did not fit the first-order model, and out-capsule residues of chlorpyrifos in soil were maintained at 1.76 (±0.33) and 5.92 (±1.20) mg/kg in the period between 15 and 60 days, respectively. The degradation kinetics of CPF-EC fit the first-order model, and the residual periods of 5 and 20mg/kg treatments were 60 days. Bacterial community structures in soil treated with two concentrations of CPF-MC showed similarity to those of the control during the test period, as seen in the band number and relative intensities of the individual band on DGGE gels (p>0.05). Fungal community structures were slightly affected in the 5mg/kg treatments and returned to the control levels after 30 days, but initially differed significantly from control in the 20mg/kg treatments (p<0.05) and did not recover to control levels until 90 days later. The CPF-EC significantly altered microbial community structures (p<0.05) and effects did not disappear until 240 days later. The results indicated that the microcapsule technology prolonged the residue periods of chlorpyrifos in soil whereas it decreased its side-effects on soil microbes as compared with the emulsifiable concentration formulation.

Asunto(s)

Cloropirifos/metabolismo , Insecticidas/metabolismo , Microbiología del Suelo , Contaminantes del Suelo/metabolismo , Secuencia de Bases , Cartilla de ADN , Composición de Medicamentos , Reacción en Cadena de la Polimerasa

RESUMEN

BACKGROUND: Flexibility in the recommended dosing time for a statin may improve patient compliance. OBJECTIVE: This study was designed to compare the efficacy and tolerability of morning and evening doses of controlled-release simvastatin in Korean adults with dyslipidemia. It was carried out as a requirement to obtain authorization from the Korean regulatory agency to market the product. METHODS: In this prospective, randomized, double-blind, multicenter, placebo-controlled Phase III study, we randomly assigned 132 patients with hypercholesterolemia to a morning-dose group or an evening-dose group. Patients in the morning-dose group received 20 mg controlled-release simvastatin in the morning and a placebo in the evening, and those in the evening-dose group received a placebo in the morning and 20 mg controlled-release simvastatin in the evening. RESULTS: After 8 weeks of the treatment, the difference in the mean change of LDL-C between the morning-dose and evening-dose groups was -2.78% (95% confidence interval, -7.65 to 2.10). The changes in total cholesterol, triglycerides, HDL-C, apolipoprotein A1, apolipoprotein B, and lipoprotein (a) after treatment did not differ between groups. Also, the achievement rates of the target LDL-C goal suggested by the dyslipidemia treatment guideline of the Korean Society of Lipidology and Atherosclerosis were not different. No serious adverse event was observed in either group. Mild and moderate adverse events were observed similarly in both groups. CONCLUSIONS: Although controlled-release simvastatin significantly reduces LDL-C levels with good tolerability in Korean adults with dyslipidemia, the time of administration does not affect its efficacy.

Asunto(s)

Anticolesterolemiantes/administración & dosificación , Hipercolesterolemia/tratamiento farmacológico , Simvastatina/administración & dosificación , Anciano , Anticolesterolemiantes/efectos adversos , Anticolesterolemiantes/uso terapéutico , LDL-Colesterol/sangre , Preparaciones de Acción Retardada , Método Doble Ciego , Esquema de Medicación , Cronoterapia de Medicamentos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Simvastatina/efectos adversos , Simvastatina/uso terapéutico , Comprimidos , Triglicéridos/sangre