Slow-release Preparation Research Articles

Synthesis of slow-release nanoparticles (CS/HNT-32) and preparation of active food packaging film

Synthesis of slow-release nanoparticles (CS/HNT-32) and preparation of active food packaging film

The β3-AR agonist BRL37344 ameliorates the main symptoms of X-linked nephrogenic diabetes insipidus in the mouse model of the disease.

X-linked nephrogenic diabetes insipidus (X-NDI) is a rare congenital disease caused by inactivating mutations of the vasopressin type-2 receptor (AVPR2), characterized by impaired renal concentrating ability, dramatic polyuria, polydipsia and risk of dehydration. The disease, which still lacks a cure, could benefit from the pharmacologic stimulation of other GPCRs, activating the cAMP-intracellular pathway in the kidney cells expressing the AVPR2. On the basis of our previous studies, we here hypothesized that the β3-adrenergic receptor could be such an ideal candidate. We evaluated the effect of continuous 24 h stimulation of the β3-AR with the agonist BRL37344 and assessed the effects on urine output, urine osmolarity, water intake and the abundance and activation of the key renal water and electrolyte transporters, in the mouse model of X-NDI. Here we demonstrate that the β3-AR agonism exhibits a potent antidiuretic effect. The strong improvement in symptoms of X-NDI produced by a single i.p. injection of BRL37344 (1 mg/kg) was limited to 3 h but repeated administrations in the 24 h, mimicking the effect of a slow-release preparation, promoted a sustained antidiuretic effect, reducing the 24 h urine output by 27%, increasing urine osmolarity by 25% and reducing the water intake by 20%. At the molecular level, we show that BRL37344 acted by increasing the phosphorylation of NKCC2, NCC and AQP2 in the renal cell membrane, thereby increasing electrolytes and water reabsorption in the kidney tubule of X-NDI mice. Taken together, these data suggest that human β3-AR agonists might represent an effective possible treatment strategy for X-NDI.

Effect of sodium alginate–gelatin–polyvinyl pyrrolidone microspheres on cucumber plants, soil, and microbial communities under lead stress

Lead is highly persistent and toxic in soil, hindering plant growth. Microspheres are a novel, functional, and slow-release preparation commonly used for controlled release of agricultural chemicals. However, their application in the remediation of Pb-contaminated soil has not been studied; furthermore, the remediation mechanism involved has not been systematically assessed. Herein, we evaluated the Pb stress mitigation ability of sodium alginate–gelatin–polyvinyl pyrrolidone composite microspheres. Microspheres effectively attenuated the Pb toxic effect on cucumber seedlings. Furthermore, they boosted cucumber growth, increased peroxidase activity, and chlorophyll content, while reducing malondialdehyde content in leaves. Microspheres promoted Pb enrichment in cucumber, especially in roots (about 4.5 times). They also improved soil physicochemical properties, promoted enzyme activity, and increased soil available Pb concentration in the short term. In addition, microspheres selectively enriched functional (heavy metal-tolerating and plant growth promoting) bacteria to adapt to and resist Pb stress by improving soil properties and nutrients. These results indicated that even a small amount (0.025–0.3 %) of microspheres can significantly reduce the adverse effects of Pb on plants, soil, and bacterial communities. Composite microspheres have shown great value in Pb remediation, and their application potential in phytoremediation is also worth evaluating to expand the application.

Preparation of Huoluo Xiaoling gel plaster and its transdermal penetration in vitro

Huoluo Xiaoling Dan is a classical prescription commonly used for blood circulation and pain relief in clinic with obvious effects. To make it directly treat lesion and improve the effect, this research optimized the preparation process of Huoluo Xiaoling gel paste and further evaluated its in vitro transdermal absorption performance, so as to provide a scientific basis for its development and utilization. Using primary viscosity, holding viscosity, and sensory score as evaluation indexes, the matrix amount of gel paste was determined by the single factor test and Box-Behnken response surface method. The ultra-performance liquid chromatography(UPLC) method was established to determine the content of eight active ingredients, including Danshensu, ferulic acid, salvianolic acid B, salvianolic acid A, ligustilide, tanshinone Ⅱ_A, 11-keto-β-boswellic(KBA), and 3-acetyl-11-keto-β-boswellic acid(AKBA). A mo-dified Franz diffusion cell method was used to evaluate and compare the absorption properties of the gel paste without volatile oil and with volatile oil microemulsion. The results showed that the optimal prescription for Huoluo Xiaoling gel paste matrix was NP700(1.35 g), glycerol(7.00 g), micropowder silica gel(1.25 g), sodium carboxymethyl cellulose(0.20 g), tartaric acid(0.06 g), and glyceryl aluminum(0.04 g). The mass fractions of eight active ingredients in the paste were successively 0.48, 0.014, 0.95, 0.39, 0.57, 0.055, 0.35, and 0.97 mg·g~(-1). The results of the in vitro transdermal absorption test showed that the addition of the volatile oil or the volatile oil microemulsion promoted the transdermal absorption of the active ingredients, and the law of drug penetration conformed to the zero equation or the Higuchi equation. The gel paste prepared by the optimal prescription has good appearance and adhesion, with no residue, and has the characteristics of skeletal slow-release preparation, which is easy to reduce the number of administration, la-ying a foundation for the development of new external dosage forms of Huoluo Xiaoling Dan.

Comparison of various calcium antagonist on vasospastic angina: a systematic review

BackgroundCoronary artery vasospasm is an abnormal spasm of coronary arteries that cause transient or complete occlusion without exertion. It causes stable angina to ACS. However, this can be prevented by...

SUDDEN CARDIOVASCULAR COLLAPSE DUE TO CALCIUM CHANNEL BLOCKER OVERDOSE: SUCCESSFUL MANAGEMENT WITH HIGH-DOSE INSULIN EUGLYCEMIC THERAPY

SUDDEN CARDIOVASCULAR COLLAPSE DUE TO CALCIUM CHANNEL BLOCKER OVERDOSE: SUCCESSFUL MANAGEMENT WITH HIGH-DOSE INSULIN EUGLYCEMIC THERAPY

Comparison of immediate and sustained release formulations of lithium salts

Lithium salts are widely used clinically, mainly for treatment of bipolar disorder, in which it is highly effective. Various preparations have been developed and tested, including older immediate-release (IR) forms of lithium carbonate and other salts and formulations with slow-release (SR) properties, developed in hopes of increasing the tolerability of lithium treatment, adherence to its use, and possibly its efficacy. Systematic reviews of head-to-head comparisons of pharmacological and clinical properties of such preparations are lacking. Accordingly, we systematically reviewed clinical studies of both IR and SR formulations of lithium salts, seeking to compare their pharmacokinetic properties, adverse effects, clinical tolerability, and clinical effectiveness. Very few such comparative studies were identified and they are highly heterogeneous in design and findings. In 11 included reports, SR formulations appeared to be better tolerated and possibly to be associated with greater adherence to treatment. Studies of comparative clinical efficacy are lacking. Despite decades of use of various lithium salts, systematic comparisons of the pharmacological and clinical properties of IR vs. SR preparations remain rare and to be deepened, though with suggestive superiority of SR salts.

Karakteristik Granul Gastroretentive Mukoadhesif Amoksisilin dengan menggunakan Kitosan-Alginat, Na.CMC dan HPMC

Gastroretentive Drug Delivery System (GRDDS) is a slow-release preparation that can be bound to the surface of epithelial cells or gastric mucosa, while mucoadhesive is one of the mechanisms of action of the Gastroretentive Drug Delivery System (GRDDS), which is a drug delivery system in which the bio adhesive polymer is combined with the drug. designed to have a longer contact with the mucous membranes in the digestive tract. This study aims to see how the characteristics of the granules that are formulated in the form of mucoadhesive gastroretentive granules. The preparation method used was wet granulation using a mucoadhesive polymer, namely chitosan-alginate with the addition of HPMC and Sodium CMC. The results showed that the velocity test of the flow rate on the granule formula F1-F8 met the flow rate requirements, the results of the F9 velocity had a poor flow rate, while the results of the angle of repose measurement in the F1, F2 and F4 formulas had good flowability, which was below 30o, different with F3, F5, F6, F7, F8, and F9 which have a 30-40o angle of repose with good flowability. The results of the particle size distribution using the stratified sieve method showed that the formulas F1-F9 were mostly retained by a mesh number 20 sieve with a size of 426-850 m. The results of the test results of the gastroretentive mucoadhesive granule preparation of amoxicillin showed that the preparation met the requirements for making granules.

Identification of a Biostimulating Potential of an Organic Biomaterial Based on the Botanical Extract from Arctium lappa L. Roots.

The development of novel biomaterials based on plant extracts is expected to boost yields without adversely affecting environmental diversity. The potential biostimulating effects have so far been underreported. The assessment of the stimulating effect of botanical biomaterials is essential in the cultivation of economically-important crops. An attempt was undertaken in this study to develop a new biostimulating material in the form of granules, based on an extract from the roots of Arctium lappa L. The scope of the research included the characterization of the new material and the identification of its biostimulating potential. The designed and produced biogranulate is rich in bioactive compounds, including polyphenolic compounds, carbohydrates, and micro- and macro-elements. The analysis of the physicochemical properties of the biomaterial has shown that it had the features of intelligent biopreparations, i.e., slow-release preparations, at the pH appropriate for legume plants. Thus, knowledge about the design of new biomaterials is a milestone in the practical development of new perspectives for enhancing sustainability in agriculture.

Recycling phosphorus from spent LiFePO4 battery for multifunctional slow-release fertilizer preparation and simultaneous recovery of Lithium

Comprehensive utilization of phosphorus from spent LiFePO4 (LFP) battery has aroused considerable interest aiming to enhance the economic profit of recycling this type of low value-added battery. In the current study, a green and novel process was developed to recover phosphorus from spent LFP battery, which was further directly converted into phosphorus grafted slow-release fertilizer (P-SRF) with acid-resistance. Meanwhile, Li was simultaneously recovered. Effect of several parameters on the leaching efficiency of P was investigated, and the properties of P-SRF in acid and neutral conditions were clarified. In the whole process, the recovery efficiencies of Li and P were more than 99.5%, and furthermore, the synthesized P-SRF had high water-absorbing capacity and low release rate in both acid and neutral conditions. Mechanism study indicated phosphorus was recovered in the form of HPO42−/H2PO4− from spent LFP battery. HPO42−/H2PO4− reduced the activation energy of the condensation reaction between urea and acrylic acid to accelerate the reaction. Meanwhile, the low release rate of P-SRF in low pH was ascribed to the buffering effects of HPO42−/H2PO4−. Furthermore, pot experiments showed P-SRF effectively promoted the growth of maize. This study provided a profitable approach for high value-added recovery of spent LFP battery, and the recovered hydrophosphate could be further transferred into P-SRF with considerable acid-resistance, which has potential application in acid soil, horticulture and slope treatment.

Supplementation with Iron in Pulmonary Arterial Hypertension. Two Randomized Crossover Trials.

Rationale: Iron deficiency, in the absence of anemia, is common in patients with idiopathic and heritable pulmonary arterial hypertension (PAH) and is associated with a worse clinical outcome. Oral iron absorption may be impeded by elevated circulating hepcidin concentrations. The safety and benefit of parenteral iron replacement in this patient population is unclear.Objectives: To evaluate the safety and efficacy of parenteral iron replacement in PAH.Methods: In two randomized, double-blind, placebo-controlled 12-week crossover studies, 39 patients in Europe received a single infusion of ferric carboxymaltose (Ferinject) (1,000 mg or 15 mg/kg if weight <66.7 kg) or saline as placebo, and 17 patients in China received iron dextran (Cosmofer) (20 mg iron/kg body weight) or saline placebo. All patients had idiopathic or heritable PAH and iron deficiency at entry as defined by a serum ferritin <37 μg/L or iron <10.3 μmol/L or transferrin saturations <16.4%.Results: Both iron treatments were well tolerated and improved iron status. Analyzed separately and combined, there was no effect on any measure of exercise capacity (using cardiopulmonary exercise testing or 6-minute walk test) or cardiopulmonary hemodynamics, as assessed by right heart catheterization, cardiac magnetic resonance, or plasma NT-proBNP (N-terminal–pro hormone brain natriuretic peptide) at 12 weeks.Conclusions: Iron repletion by administration of a slow-release iron preparation as a single infusion to patients with PAH with iron deficiency without overt anemia was well tolerated but provided no significant clinical benefit at 12 weeks.Clinical trial registered with ClinicalTrials.gov (NCT01447628).

Aspiration in lethal drug abuse\u2014a consequence of opioid intoxication

AimsThe primary objective of this study was to investigate whether the fatalities of opioid abuse are not only related to respiratory depression but also as a result of other side effects such as emesis, delayed gastric emptying, a reduction of the cough reflex, and impaired consciousness leading to the aspiration of gastric contents, a finding regularly observed in drug-related deaths.DesignA retrospective exploratory study analyzing heroin/morphine/methadone-related deaths submitted to court-ordered autopsy.SettingCenter for Forensic Medicine, Medical University of Vienna, Austria (2010–2015).ParticipantsTwo hundred thirty-four autopsy cases were included in the study: morphine (n = 200), heroin (n = 11), and methadone (n = 23) intoxication.FindingsAnalyses revealed that 41.88% of all deceased showed aspiration of gastric contents with equal gender distribution (p = 0.59). Aspiration was more frequent in younger deceased (χ2 = 8.7936; p = 0.012) and in deceased with higher body mass index (BMI) (χ2 = 6.2441; p = 0.044). Blood opioid concentration was lower in deceased with signs of aspiration than in non-aspirators (p = 0.013). Toxicological evaluation revealed a high degree of concomitant substance abuse (91%)—benzodiazepines (61.6%) and/or alcohol (21.8%).ConclusionsThere are lower opioid concentrations in deceased with signs of aspiration, a fact which strongly points to aspiration as alternative cause of death in opioid-related fatalities. Furthermore, this study highlights the common abuse of slow-release oral morphine in Vienna and discusses alternative medications in substitution programs (buprenorphine/naloxone or tamper-resistant slow-release oral morphine preparations), as they might reduce intravenous abuse and opioid-related deaths.

LT4 and Slow Release T3 Combination: Optimum Therapy for Hypothyroidism?

ContextLevothyroxine (LT4) is recommended as replacement therapy for thyroid hormone deficiency. However, some hypothyroid patients receiving LT4 therapy do not feel as well as healthy subjects. This article aimed to review current knowledge regarding LT4 monotherapy versus LT4+LT3 combination therapy and propose future directions regarding LT4+slow release T3 combination treatment for hypothyroidism.Evidence AcquisitionWe searched PubMed and Scopus using related keywords.ResultsThe LT4 monotherapy causes higher serum free T4 (fT4), subnormal serum free T3 (fT3), and fT3/fT4 ratio in one-fourth of patients. The LT4+LT3 combination therapy increases serum T3 and fT3 concentrations and may normalize the fT3/fT4 ratio. However, the primary outcomes, including thyroid hormone deficiency, anxiety, depression, and quality of life, may not be better in LT4+LT3 combination therapy than in LT4 monotherapy. Recent surveys show that combination therapy is on the rise, in particular, due to patient demand. The LT4 plus slow-release LT3 preparation has shown promising results in improving serum thyroid hormone concentrations.ConclusionsThe beneficial effect of LT4+LT3 combination therapy is not clear, and the safety of long-term therapy is yet under question. More scientific well-designed research projects are required in this field.

FORMULATION A CIPROFLOXACIN HYDROCHLORIDE EXTENDED-RELEASE TABLET WITH COMBINATION OF HYDROXYPROPYL METHYLCELLULOSE (HPMC) K100M AND HYDROXYPROPYL METHYLCELLULOSE (HPMC) K4M BY DIRECT COMPRESSION METHOD

Objective: Ciprofloxacin hydrochloride tablets which are not extended-release will produce non-constant drug levels in the blood. This study aimed to overcome this problem by making ciprofloxacin hydrochloride extended-release tablets with a combination of hydroxypropyl methylcellulose (HPMC) K100M and hydroxypropyl methylcellulose (HPMC) K4M by a direct compression method.&#x0D; Methods: The method in this study consisted of preformulation, formula design, manufacture of ciprofloxacin hydrochloride tablets, tablet print mass testing, IPC (In-Process Control) slow-release tablet mass print, IPC (In-Process Control) quality of slow-release tablet preparation, dissolution test, and statistical analysis. Preformulation was carried out aiming to determine the physical and chemical properties of active-excipient substances based on a certificate of analysis. This was done using a Fourier Transform Infrared (FT-IR) and UV-Vis spectrophotometer. Five kinds of ciprofloxacin hydrochloride tablet formulations were made using the direct pressing method with variations in the concentration of HPMC K100M and HPMC K4M. The ratio of percentage of HPMC K100M and HPMC K4M were F1 0,5%: 1%, F2 1%: 0,5%, F3 0,75%: 0,75%, F4 1%: 0%, F5 0%: 3%. Evaluation of tablet preparations (IPC control) included weight uniformity test, size uniformity test, hardness test, and friability test. The dissolution test was carried out for 2 h by hydrochloride acid 0,1 N pH 1.2 as (pH of gastric acid). Statistical analysis using Perfect Block Random Design (PBRD) method and further testing using the Newman-Keuls test was applied for the data obtained.&#x0D; Results: The test results with FTIR showed that ciprofloxacin hydrochloride used compared to ciprofloxacin hydrochloride BPFI is equivalent and has a purity index of 0.992739. Determination of the level of the active ingredient ciprofloxacin hydrochloride was carried out by measuring the absorbance of a 5 ppm sample solution at a wavelength of 276 nm. The percentage of absorbance of the solution is then calculated and the result obtained is 98.87%. The range of levels that have been set is 98%-102%. These test results were under those listed on the certificate of analysis. The results of the IPC test in the form of weight uniformity test, size uniformity test, hardness test, friability test, and uniformity of ciprofloxacin hydrochloride levels in the preparation, showed all data obtained fulfilling the requirements set by USP 36 convention (2013). The result from dissolution tablet test on 30, 60, and 120 min showed the release of active substance on F1 56.00 %, 67.76 %, and 87.57 %. F2 were 53.42 %, 65.16 %, and 91.44 %. F3 were 59.18 %, 72.15 %, and 91.20 %. F4 were 50.51 %, 70.70 %, and 95.29 %. F5 were 53.75 %, 69.55 %, and 92.05 %. Statistical analysis was applied for the data obtained. Dissolution results illustrated the level of active substances dissolved in the dissolution medium for 2 h or in other words the dissolution test results indicated the number of active substances from tablets that were released and enter the digestive tract and came in contact with body fluids.&#x0D; Conclusion: The dissolution test results as a basis of extended-release tablets showed all of the formulae met dissolution requirements of the United States Pharmacopeia (USP) 36 convention.

Opioid prescribing in the emergency department of a tertiary hospital: A retrospective audit of hospital discharge data.

EDs are a common source of prescription opioids on discharge. We explored opioid prescribing practices in an ED at a tertiary hospital in Victoria, Australia. A retrospective audit over a 6 month period of patients discharged from the ED to the community with the maximum allowable quantities of prescription opioids. There was a total of 3301 patient-episodes discharged with a prescription from the ED. Of these, 766 (23.2%, 95% confidence interval [CI] 21.8-24.6) were prescribed opioids, with over half discharged with the maximum allowable quantities of prescription opioids. Immediate-release opioids were prescribed in 362 (85.8%, 95% CI 82.5-89.1) patient-episodes, a combination of immediate-release and slow-release preparations were prescribed in 29 (6.9%, 95% CI 4.5-9.3) and 31 (7.3%, 95% CI 4.8-9.8) were prescribed as slow-release opioids alone. Co-prescription of other analgesia with opioids occurred in 152 (36.0%, 95% CI 31.4-40.6) patient-episodes. Possible drug interactions between opioids and other medications were noted in 117 (27.7%, 95% CI 23.4-32.0) patient-episodes. Discharge summaries were prepared for 360 (85.3%, 95% CI 81.9-88.7) patient-episodes, but only 171 (40.5%, 95% CI 35.8-45.2) included a plan to address the opioids, be that an opioid-weaning regimen, analgesia review or referral to a pain specialist on discharge. Opioid prescribing was common in this ED, with almost one-quarter of discharge prescriptions being for a prescription opioid. This audit highlights potential areas for practice improvement including review of the quantity of opioid tablets prescribed as well as an opioid plan on discharge from the ED.

Simplified superovulation protocols in dromedary camels (Camelus dromedarius)

This study was conducted to develop simple superovulation protocols in dromedary camels. Using two commercial FSH products, a series of experiments was conducted to evaluate the effect of different superovulation protocols on ovarian response and embryo production. In experiment 1, camels in control group (n = 15) received 400 mg Folltropin-V in a traditional protocol (FSH diluted in saline and given twice daily in decreasing doses over 5 days) and camels in split-injection (2 doses 48 h apart) groups received either 400 (n = 16, first dose: 320 mg, second dose: 80 mg) or 200 mg (n = 16, first dose: 120 mg, second dose: 80 mg) of slow-release (SR) preparation of Folltropin-V [Folltropin-V diluted in hyaluronan (5 mg/mL) solution]. In experiment 2, camels in control group (n = 13) received 2000 IU Pluset in a traditional protocol and camels in split-injection groups received either 2000 (n = 14, first dose: 1600 IU, second dose: 400 IU) or 1000 IU (n = 16, first dose: 600 IU, second dose: 400 IU) of SR preparation of Pluset (Pluset diluted in hyaluronan solution). In experiment 3, camels received SR preparation of 200 mg Folltropin-V (n = 45, first dose: 120 mg, second dose: 80 mg) or 1000 IU Pluset (n = 42, first dose: 600 IU, second dose: 400 IU) in a split-injection protocol. In experiments 1 and 2, the mean number of ovulations, corpora lutea, transferable embryos and unfertilized ova were similar (P > 0.05) between groups. In experiment 3, there was no difference (P > 0.05) between SR preparations of Folltropin and Pluset on the number of ovulatory sized (≥9 mm) follicles (15.8 ± 0.9 vs 16.7 ± 0.9) and transferable embryos (5.0 ± 0.4 vs 5.2 ± 0.5). In conclusion, split-injection of SR preparation of FSH resulted in a similar superovulatory response compared to a traditional protocol and a similar superovulatory response can be achieved with SR preparations of Folltropin-V and Pluset in a split-injection protocol.

Oocyte developmental competence is improved by relatively greater circulating progesterone concentrations during preovulatory follicular growth

This study evaluated the effect of progesterone priming during follicular growth on oocyte competence to undergo oocyte cleavage and embryo development in sheep. Two experiments were performed on a total of 195 females that either received or did not receive a progesterone treatment (CIDR-type device) during the first follicular wave, beginning soon after ovulation (i.e., Day 0 of the experiment). On Day 3, the follicular population and oocyte quality (Experiment 1 and 2) and the competence of oocytes for cleavage and embryo development (Experiment 2) were evaluated after laparoscopic ovum pickup (LOPU) and in vitro fertilization. In Experiment 1, in a 2 × 2 factorial study the progesterone priming treatment (treated or not) was or was not associated with a single dose of FSH in a slow-release hyaluronic acid preparation given on Day 0. The follicular population on Day 3 and the number and morphology of recovered cumulus oocyte complexes (COCs) were not affected by the progesterone treatment (P = NS) but were improved by the FSH administration (P < 0.05). An interaction between both treatments was observed (P < 0.05), with more desirable outcome with the females that received both the progesterone and the FSH treatments. In Experiment 2, half of the females received the exogenous progesterone priming, and all females received FSH on Day 0. After follicular aspiration on Day 3, the cleavage rate and the embryo development rate following in vitro fertilization and culture were greater in those females that received the progesterone treatment (P < 0.05). In conclusion, these studies provide evidence that progesterone treatment during follicular growth affects oocyte competence, with the greater progesterone concentrations enhancing the oocyte’s capacity to undergo cleavage and embryo development.

Slow-release praziquantel for dogs: presentation of a new formulation for echinococcosis control

BackgroundEchinococcosis is a serious, zoonotic, parasitic disease with worldwide distribution. According to a epidemiological survey in 2012 in China, there are 20,000 infected patients and more than 50 million people at the risk. As the dog is the main, definitive host, the Government of China encourages monthly praziquantel treatment of every dog. However, this is difficult to achieve in geographically challenging areas, such as the Tibetan plateau, where there are also many dogs without owners. To overcome these problems, we investigated the transmission blocking capacity of a slow-release formulation of praziquantel administered by subcutaneous injection.MethodsThe impact of a slow-release preparation of two pharmacokinetically stereoselective praziquantel enantiomers, i.e., R-(−)-praziquantel (R-PZQ) and S-(+)-praziquantel (S-PZQ) absorbed into a biodegradable polymer was studied in beagle dogs (N = 6). The preparation was given by subcutaneous injection using a single dose of 100 mg/kg. Chiral-selective, high-performance liquid chromatography (HPLC) and high-resolution mass spectrometry (HRMS) were applied to measure the praziquantel enantiomers in the plasma of the dogs. The lower limit for estimating plasma concentrations accurately for R-PZQ was 4 ng/ml and for S-PZQ 20 ng/ml. The pharmacokinetic parameters were calculated by a noncompartmental analysis model using Drug Analyze System (DAS) software 2.0. The SPSS 19.0 software was used for statistical analysis, and the statistical comparison between enantiomers was assessed using the two-tailed t-test.ResultsTwo hours after administration, peak concentrations of R-PZQ and S-PZQ: 321 ± 26 and 719 ± 263 ng/ml, respectively, were achieved. After 180 days, the average plasma concentration of R-PZQ in the six dogs had decreased to 13 ng/ml. The average concentration value of S-PZQ was higher than that of R-PZQ in the first 90-day period but fell afterwards and could not be accurately estimated when dropping below 20 ng/ml (the lower methodological limit for this enantiomer). Taking all the dogs into account, the average maximum concentration (Cmax) of S-PZQ in plasma over the first 3 months was higher than that of R-PZQ by 114.0% (P < 0.05), while the average mean retention time (MRT) of R-PZQ in plasma was higher than that of S-PZQ by 96.3% (P < 0.05).ConclusionsPraziquantel given as an in situ slow-release formulation by subcutaneous injection resulted in concentrations of the active principle in beagle dogs, which should be capable of resisting new Echinococcus infections for at least 6 months. The new formulation of praziquantel represents a potential, alternative way of presenting medication against tapeworm infections in dogs.

Iron deficiency in cancer patients.

Anemia is a frequent complication in cancer patients, both at diagnosis and during treatment, with a multifactorial etiology in most cases. Iron deficiency is among the most common causes of anemia in this setting and can develop in nearly half of patients with solid tumors and hematologic malignancies. Surprisingly, this fact is usually neglected by the attending physician in a way that proper and prompt investigation of the iron status is either not performed or postponed. In cancer patients, functional iron deficiency is the predominant mechanism, in which iron availability is reduced due to disease or the therapy-related inflammatory process. Hence, serum ferritin is not reliable in detecting iron deficiency in this setting, whereas transferrin saturation seems more appropriate for this purpose. Besides, lack of bioavailable iron can be further worsened by the use of erythropoiesis stimulating agents that increase iron utilization in the bone marrow. Iron deficiency can cause anemia or worsen pre-existing anemia, leading to a decline in performance status and adherence to treatment, with possible implications in clinical outcome. Due to its frequency and importance, treatment of this condition is already recommended in many specialty guidelines and should be performed preferably with intravenous iron. The evidences regarding the efficacy of this treatment are solid, with response gain when combined with erythropoiesis stimulating agents and significant increments in hemoglobin as monotherapy. Among intravenous iron formulations, slow release preparations present more favorable pharmacological characteristics and efficacy in cancer patients.

MT1 and MT2 Melatonin Receptors: A Therapeutic Perspective.

Melatonin, or 5-methoxy-N-acetyltryptamine, is synthesized and released by the pineal gland and locally in the retina following a circadian rhythm, with low levels during the day and elevated levels at night. Melatonin activates two high-affinity G protein-coupled receptors, termed MT1 and MT2, to exert beneficial actions in sleep and circadian abnormality, mood disorders, learning and memory, neuroprotection, drug abuse, and cancer. Progress in understanding the role of melatonin receptors in the modulation of sleep and circadian rhythms has led to the discovery of a novel class of melatonin agonists for treating insomnia, circadian rhythms, mood disorders, and cancer. This review describes the pharmacological properties of a slow-release melatonin preparation (i.e., Circadin®) and synthetic ligands (i.e., agomelatine, ramelteon, tasimelteon), with emphasis on identifying specific therapeutic effects mediated through MT1 and MT2 receptor activation. Discovery of selective ligands targeting the MT1 or the MT2 melatonin receptors may promote the development of novel and more efficacious therapeutic agents.