جستجوی مقالات مرتبط با کلیدواژه « pharmacokinetics » در نشریات گروه « پزشکی »

Natural herbs have garnered significant research recently as their components target multiple disease signaling pathways, making them highly potential for various disease prevention and treatment. Embelin, a naturally occurring benzoquinone isolated from Embelia ribes, has shown promising biological activities such as antitumor, antidiabetic, anti-oxidant, and antimicrobial. Various mechanisms have been reported, including monitoring genes that synchronize the cell cycle, up-regulating multiple anti-oxidant enzymes, suppressing genes that prevent cell death, influencing transcription factors, and preventing inflammatory biomarkers. However, the hydrophobic nature of embelin leads to poor absorption and limits its therapeutic potential. This review highlights a wide range of nanocarriers used as delivery systems for embelin, including polymeric nanoparticles, liposomes, nanostructured lipid carriers, micelles, nanoemulsion, and metallic nanoparticles. These embelin nanomedicine formulations have been developed in preclinical studies as a possible treatment for many disorders and characterized using various in vitro, ex vivo, and in vivo models.

The development in molecular pharmacotherapy and enhanced comprehension of disease mechanisms have necessitated the precise targeting of cells responsible for initiating and advancing illnesses. This is particularly true for the majority of life-threatening illnesses that need treatment medicines with many adverse effects. Therefore, precise tissue targeting is crucial to avoid systemic exposure. Modern drug delivery systems (DDS) are created utilizing cutting-edge technology to expedite the administration of drugs across the body to a particular target area, optimizing the effectiveness of treatment and reducing the build-up of drugs in unintended areas. Consequently, they significantly impact the management and therapy of diseases. Recent drug delivery systems (DDS) have significant benefits over older methods in improved performance, automation, accuracy, and effectiveness. Nanotechnology and nano-delivery techniques are emerging fields of study that focus on using materials at the nanoscale to function as diagnostic instruments or transport therapeutic drugs to particular targeted areas in a controlled way. This review provides an up-to-date overview of recent progress in nanotechnology and drug delivery methods based on nanotechnology. It thoroughly examines the use of nanomaterials to enhance the effectiveness of new and existing drugs, including natural products, and their role in targeted diagnosis using disease indicator molecules.

In Traditional Persian Medicine (TPM) saffron is used as an accompaniment agent “Mobadreq” in poly herbal formulations. According to TPM texts, “Mobadreq” is a substance (or drug) which facilitates access of drugs or food to the whole body or specific organs. This study investigated the effect of oral co-administration of Crocus sativus L. (saffron) on the absorption and some pharmacokinetic parameters of acetaminophen in rats. Two groups of Rats (n=6) were treated by 1: acetaminophen 10 mg/kg along with Crocus sativus 4 mg/kg (test group) and 2: 10 mg/kg acetaminophen (control). The plasma concentrations of acetaminophen after oral administration (at 0, 5, 10, 15, 20, 40, 60, 90, and 120 min) were monitored by an HPLC-UV method. Results indicated that the plasma concentration of acetaminophen in the test group was reached to the maximum concentration (Cmax) faster than control group. As a result, at 5 to 40 minutes after drug gavage, the concentration of acetaminophen in both groups was significantly different.  It was also found that co-administration of acetaminophen and saffron significantly increased acetaminophen’s area under concentration curve (AUC0-60) in compare to the acetaminophen alone (p<0.025). These results suggested that saffron could increase absorption rate of acetaminophen. Consequently, saffron can be considered and introduced as an enhancer of absorption rate and efficacy of acetaminophen and other drugs at least by oral route although the drug interactions with this herb should be considered.

Pregnancy is a critical stage in oral health of women. The storm of hormones in pregnancy usually cause gingival problems and tooth decay. On the other hand, poor oral health during pregnancy may lead to complications such as premature delivery and preeclampsia. However, while a routine dental care is necessary during pregnancy, drug therapy may be required in some cases such as pain control or management of dental procedures or oral infections. In a pregnant patient requiring dental care, the agents routinely prescribed should be evaluated for potential risks to the mother and/or fetus. On the other hand, many physiological changes occur dur ing pregnancy to support the needs of the developing fetus and these changes can affect the efficacy and pharmacokinetics of drugs as well.
This article aims to provide a comprehensive review of dental drug therapy in pregnancy, including safety and recommendations for commonly used medications in dental practice. The physiological changes during pregnancy and their impact on oral health and drug therapy are discussed with an emphasize on dental therapeutic agents which can be selected in treatment of pregnant patients.

Pediatric patients have very different pharmacokinetic and pharmacodynamic profiles compared to adults. A number of anatomical and physiological factors determine the pharmacokinetic profile of a drug. Differences in physiology in pediatric populations compared with adults can influence the concentration of drug within the plasma or tissue. When considering medication for a child or adolescent, one should be cautious about extrapolating from adult studies or practices. Always remember, children are not small adults. Children tend to have higher rates of metabolism and elimination than adults. As a result, children generally require higher weight-adjusted doses of most medications to achieve similar blood levels as adults. As pharmacokinetics is hard to predict in children, and thus a ‘start low and go slow’ approach is important. This review details key pharmacological and practical considerations which a healthcare professional should be aware of to understand consequences of drug use and dose adjustments in infants and children.

The objective of the study was to evaluate the pharmacokinetics of a single oral dose of 300 mg gabapentin capsule in an Iranian healthy population. The study was a standard two-way, crossover, randomized, and single-dose study with one-week washout period in 24 healthy volunteers who received 300 mg gabapentin capsules (test and reference formulation). After drug administration, blood samples were taken according to the planned times over a period of 24 hours. The plasma concentrations of gabapentin were determined using the validated high-performance liquid chromatography (HPLC) method with ultraviolet (UV) detection. All the pharmacokinetic parameters for gabapentin in healthy volunteers were calculated using nonlinear mixed-effect modeling and standard non-compartmental methods. A one-compartment model with a first-order absorption rate and first-order elimination rate with a proportional error model described the pharmacokinetics of gabapentin. Values (relative standard error (RSE) %) for first-order absorption rate constant (Ka), oral clearance (Cl/F), and apparent volume of distribution (Vd/F) were 1.08 (7.23) 1/h, 6.72(0.29) L/h, and 73.82(5.10) L. The mean estimate for non-compartmental pharmacokinetic parameters including maximum plasma concentration (Cmax), the area under the curve to the last quantifiable concentration (AUCt), and the area under the curve to the infinity (AUCinf) was calculated. Cmax for test and reference formulation was 3850 ng/mL and 3856 ng/mL respectively. The AUCt for test and reference formulation was 39549 ng. h/mL and 40249 ng. h/mL respectively. The AUCinf for test and reference formulation was 47161 ng. h/mL and 633424 ng. h/mL respectively. The median (range) for the time to peak plasma gabapentin concentration (Tmax) for the test and refer ence drug was 3 (1.5-6) hours and 3 (1.5-5) hours respectively. The mean (standard deviation) elimination half-life (t1/2) of gabapentin for the test and reference drug was 9.39 (2.75) hours and 8.88 (2.48) hours. They were all within the acceptable range of 80-125%, consequently, we concluded that the two gabapentin formulations were bioequivalent. Our results confirmed that the gabapentin pharmacokinetic model in the Iranian healthy population was similar to other studied populations. However, we could not find any influential covariate to explain the inter-individual variability of parameters.

 Gestodene (GEST) is widely used in female contraception. It is currently being used as an oral contraceptive. However, unfortunately, oral contraceptives are often associated with several bothersome side effects and poor compliance. Therefore, a sustained delivery system for GEST to overcome these shortcomings is highly desirable.

 The present study successfully developed a kind of novel dissolving microneedles (DMNs) with a potential for sustained release and a minimally invasive intradermal treatment of GEST.

 The dissolving microneedles containing GEST were fabricated using polyvinylpyrrolidone as the base material. The characteristics in vitro and pharmacokinetics in vivo of GEST-loaded DMNs were investigated.

 The results showed that the microneedle could pierce the porcine skin and release the drug at an average dose of 20µg/cm2 daily for seven days. The pharmacokinetic experiment of the microneedles indicated that the plasma level of GEST in rats increased with increasing drug dosage, and the plasma drug concentration-time curves were much flatter compared with subcutaneous injection and oral administration. In addition, no cutaneous irritation was observed.

 GEST-loaded DMNs may be a promising intradermal sustained delivery system for contraceptive use.

 Cerasomes, due to their external siloxane network, demonstrate markedly higher physicochemical stability and, therefore, easier handling and storage than liposomes.

 The main objective of this study was to compare the pharmacokinetics (PK) of cerasome and liposome following intravenous administration. The PK of PEGylated and non-PEGylated cerasomes was also compared to see whether the presence of a hydrophilic siloxane network on the surface of cerasomes can play the role of polyethylene glycol (PEG) in increasing the blood circulation of these vesicles.

 Silver sulfide (Ag2S) quantum dots (Qds)-loaded PEGylated and non-PEGylated cerasomes and PEGylated liposomes were fabricated and thoroughly characterized in terms of particle size, polydispersity index, zeta potential, entrapment efficiency, and in vitro stability. For pharmacokinetic evaluation, the free Qds and the selected formulations were intravenously injected into rats, and blood samples were collected for up to 72 hours. Pharmacokinetic parameters were calculated by the non-compartmental method.

 Both cerasomal and liposomal carriers significantly improved the PK of Qds. For example, the elimination half-life (t1/2) and the area under the plasma concentration-time curve from time 0 to time infinity (AUC0-∞) for the free Qds were 4.39 h and 8.01 µg/mL*h and for cerasomal and liposomal formulations were 28.82 versus 26.95 h and 73.25 versus 62.02 µg/mL*h, respectively. However, compared to each other, the plasma concentration-time profiles of PEGylated cerasomes and liposomes displayed similar patterns, and the statistical comparison of their pharmacokinetic parameters did not show any significant difference between the two types of carriers. For PEGylated cerasomes, t1/2 and AUC0-∞ values were respectively 1.6 and 3.3 times greater than the classic cerasome, indicating that despite the presence of a hydrophilic siloxane network, the incorporation of PEG is necessary to reduce the clearance of cerasomes.

 The comparable PK of PEGylated cerasomes and liposomes, along with the higher physicochemical stability of cerasomes, can be considered an important advantage for the clinical application of cerasomes. Additionally, the easy surface functionalizing ability of cerasomes confers a dual advantage over liposomes. The study findings also showed that the presence of a hydrophilic siloxane network on the surface of cerasomes alone is not enough to make them circulate long.

 Amphotericin B (AmB) is the first-line drug to treat invasive fungal infections. However, its delivery to the body and clinical use faces many challenges because of its poor solubility, poor pharmacokinetics, and severe nephrotoxicity.

 Due to the necessity for designing safer and more effective nanocarriers for AmB and the importance of preclinical pharmacokinetic studies in evaluating these novel drug delivery systems, the present study was framed to explore the influence of rat strain on the pharmacokinetic profile of this drug.

 Twenty-four Wistar and Sprague–Dawley (SD) rats were intravenously injected with 1 mg/kg AmB as Fungizone or AmBisome, which are the two most commonly marketed formulations of the drug. Blood samples were collected before and at regular intervals up to 24 h after administration. Drug concentration was analyzed by a validated HPLC method, and pharmacokinetic parameters were determined by the non-compartmental method.

 Irrespective of the type of formulation, the AUC0-t and AUC0-∞ values were significantly higher (P < 0.001), and Cl as an important PK parameter was markedly lower (P < 0.001) in SD rats compared to the Wistar strain. For Fungizone, the mean Cl values in SD and Wistar rats were 206.90 and 462.95 mL/h/kg (P < 0.001), respectively. The apparent volume of distribution (Vss) was also lower in SD rats compared to Wistar; however, for AmBisome, the difference in Vss was not statistically significant. Our further investigation suggested that the higher amount of total protein in the SD strain may justify the higher plasma concentrations and lower Cl and Vss of amphotericin B in this strain compared to the Wistar strain.

 Overall, following intravenous administration of AmB, there were significant differences in the pharmacokinetic parameters of the drug between two rat strains for both formulations. The obtained data is important for correctly interpreting experimental data from different research groups.

Post-translational modifications in bioprocessing and storage of recombinant mAbs are the main sources of charge variants. While the profile of these kinds of variants is considered an important attribute for the therapeutic mAbs, there is controversy about their direct role in safety and efficacy. In this study, the physicochemical and pharmacokinetic (PK) properties of the separated charge variants belonging to a trastuzumab potential biosimilar, were examined.

The acidic peaks, basic peaks, and main variants of trastuzumab were separated and enriched by semi-preparative weak cation exchange. A panel of analytical techniques was utilized to characterize the physicochemical properties of these variants. The binding affinity to HER2 and FcγRs and the PK parameters were evaluated for each variant.

Based on the results, the charge variants of the proposed biosimilar had no significant influence on the examined efficacy and PK parameters.

During the development and production of biosimilar monoclonal antibodies, evaluating the effect of their charge variants on efficacy and PK parameters is needed.

Multiple sclerosis (MS) is a central nervous system (CNS) chronic disease in which axons are demyelinated and signal conduction is slowed or blocked. Unfortunately, current drugs that are used to treat MS have limited efficiency and considerable side effects. The use of bioactive natural products for treating neurodegenerative diseases has become of great interest due to their multimodal mechanism of action and potential safety. However, pharmacokinetic parameters such as bioavailability, absorption, metabolic pathways, and elimination routes are essential for evaluating the efficacy and toxicity of herbal medicines and herbal preparations in the clinic. In this review, we have summarized different pharmacokinetic parameters of neuroprotective natural products with anti-experimental autoimmune encephalomyelitis (EAE) effects and recent developments in strategies to improve their bioavailability and effectiveness.

In the setting of impaired liver function, estimation of glomerular filtration rate (GFR) using common creatinine-based equations is inaccurate. Recently, the Glomerular filtration Rate Assessment In Liver disease (GRAIL) model has been introduced to estimate GFR in liver transplantation. This study was conducted to compare vancomycin dose adjustment in liver transplant patients using Cockcroft-Gault (C-G) versus the GRAIL method.

In this pilot, randomized clinical trial, adult liver transplant recipients who were a candidate to receive intravenous vancomycin were enrolled. The level of kidney function was estimated using the GRAIL model and C-G equation in the intervention and control arms, respectively. Then, vancomycin maintenance doses were accordingly adjusted. At the steady state, peak and trough serum concentrations of vancomycin were collected for area under the concentration-time curve (AUC) calculation and pharmacokinetic comparisons.

Fifteen patients were enrolled in each arm of study. The mean daily dose of vancomycin was estimated insignificantly lower for individuals in the GRAIL arm than the C-G group (1550.00±544.45 mg versus 1750.00± 389.60 mg). Compared with the C-G group, a higher rate of patients in the GRAIL arm experienced below-target vancomycin trough concentrations (40.0% versus 13.3%), and a lower rate showed above target trough concentration (40.0% versus 66.7%). These differences did not reach statistical significance. Individuals in the GRAIL arm represented a significantly higher rate of below target vancomycin AUC/MIC than patients in the C-G arm (46.7% versus 6.7%) (P=0.049). No differences in clinical outcomes were observed between the two groups.

Using the GRAIL model for vancomycin dosing may result in less percent of patients with at target AUC/MIC compared to the C-G method and expose more patients at risk for vancomycin under dosing.

Medicinal plants having antioxidant potential possess numerous constituents which are responsible for different beneficial effects and are used as an alternative resource of medicine to lessen diseases linked with oxidative stress. Flavonoids are identified in the plants since ages and display wide spectrum of biological actions that might be able to stimulate the steps which are disturbed in different diseases. Flavonoids are significant natural compounds with various biologic properties, among which the most common is the anti-oxidant potential.Citrus flavonoids establish an important stream of flavonoids. Naringin, very common flavonoids present in the diet, belongs to the family of flavanone. It is the principal constituent of citrus family that contains flavonoids for example tomatoes, grapefruits and oranges.

In this article, we reviewed naringin with respect to sources, chemical property, pharmacokinetics, pharmacological activity, and novel formulations. The literature survey has been done by searching different databases such as Psyc INFO, Science Direct, PubMed, EMBASE, Google, Google Scholar, Medline.

Naringin is known to behave as an antioxidant and possess anti-inflammatory, anti-apoptotic, anti-atherosclerotic, neuroprotective, anti-psychotic, anti-asthmatic, anti-diabetic, hepatoprotective, anti-tussive, cardioprotective, and anti-obesity activity. Further clinical studies using large sample sizes remain essential to obtain the appropriate dose and form of naringin for averting diseases. Furthermore, the therapeutic approach of these bioflavonoids is significantly inappropriate due to the lack of clinical evidence. Different plants must be explored further to find these bioflavonoids in them.

The results of this exploration provides biological actions of bioflavonoid (naringin), predominantly on pharmacological and novel dosage forms of naringin.

Diabetes mellitus (DM) affects the pharmacokinetics of drugs. Ranolazine is an antianginal drug that is prescribed in DM patients with angina. We decided to evaluate the effect of DM on the pharmacokinetics of ranolazine and its major metabolite CVT-2738 in rats. Male rats were divided into two groups: DM (induced by 55 mg/kg Streptozotocin (STZ)) and non-DM. All animals were treated with 80 mg/kg of ranolazine for 7 continuous days. The blood samples were collected immediately at 0 (prior to dosing), 1, 2, 3, 4, 8, and 12 hr after administration of the 7th dose of ranolazine. Serum ranolazine and CVT-2738 concentrations were determined using the high-performance liquid chromatography (HPLC) method. Pharmacokinetic parameters were calculated using a non-compartmental model and compared between the two groups. The peak serum concentration (Cmax) and area under the curve (AUC) of ranolazine significantly decreased in DM compared with non-DM rats. DM rats showed significantly higher volumes of distribution (Vd) and clearance (CL) of ranolazine than non-DM rats. DM did not affect Ke, Tmax, and T1/2 of ranolazine. The concentration of metabolite was lower than the HPLC limit of detection (LOD). It was found that streptozotocin-induced DM increased Vd and CL of ranolazine, thereby decreasing the AUC of the drug. Therefore, dosage adjustment may be necessary for DM patients, which requires further clinical studies.