Teresa Dalla Costa

Universidade Federal do Rio Grande do Sul | UFRGS · Faculty of Pharmacy

Schizophrenia (SCZ) response to pharmacological treatment is highly variable. Quetiapine (QTP) administered as QTP lipid core nanocapsules (QLNC) has been shown to modulate drug delivery to the brain of SCZ phenotyped rats (SPR). In the present study, we describe the brain concentration-effect relationship after administrations of QTP as a solution...

We previously reported that ciprofloxacin (CIP) free lung interstitial concentrations are decreased by biofilm-forming Pseudomonas aeruginosa pulmonary chronic (14 d) infection. To get a better understanding on the influence of infection on CIP lung distribution, in the present study free lung interstitial fluid and epithelial lining fluid (ELF) co...

A population pharmacokinetic model was developed to describe alterations in ceftaroline brain disposition caused by meningitis in healthy and methicillin-resistant Staphylococcus aureus (MRSA)-infected rats. Blood and brain microdialysate samples were obtained after a single bolus dose of ceftaroline fosamil (20 mg/kg) administered intravenously. P...

Objectives Methotrexate (MTX) is subject to therapeutic drug monitoring because of its high pharmacokinetic variability and safety risk outside the therapeutic window. This study aimed to develop a population pharmacokinetic model (popPK) of MTX for Brazilian pediatric acute lymphoblastic leukemia (ALL) patients who attended the Hospital de Clínica...

A bioanalytical LC-MS/MS method was developed and validated to determine ceftaroline in microdialysate samples from plasma and brain. Ceftaroline was separated using a C18 column and a mobile phase consisting of water and acetonitrile, both with 5 mM of ammonium formate and acid formic 0.1%, eluted as gradient. Ceftaroline was monitored using elect...

Unsuccessful anesthesia often occurs under an inflammatory tissue environment, making dentistry treatment extremely painful and challenging. Articaine (ATC) is a local anesthetic used at high (4%) concentrations. Since nanopharmaceutical formulations may improve the pharmacokinetics and pharmacodynamics of drugs, we encapsulated ATC in nanostructur...

Ceftaroline, approved to treat skin infections and pneumonia due to methicillin-resistant Staphylococcus aureus (MRSA), has been considered for the treatment of central nervous system (CNS) infections. A population pharmacokinetic (popPK) model was developed to describe ceftaroline soft tissue and cerebrospinal fluid (CSF) distributions and investi...

Using cycloalkyl and electron-donating groups to decrease the carbonyl electrophilicity, a novel series of 2-(quinoline-4-yloxy)acetamides was synthesized and evaluated as in vitro inhibitors of Mycobacterium tuberculosis (Mtb) growth. Structure-activity relationship studies led to selective and potent antitubercular agents with minimum inhibitory...

Purpose: 5'-methoxynobiletin (5'-MeONB), a polymethoxyflavone isolated from A. conyzoides, has shown anti-inflammatory property. Nevertheless, the antinociceptive activity and pre-clinical pharmacokinetics (PK) characteristics of 5'-MeONB remain unknown. Considering the anti-inflammatory potential of the 5'-MeONB, this study aimed to investigate t...

Biofilms and infectious process may alter free antimicrobial concentrations at the site of infection. Tobramycin (TOB), an aminoglycoside used to treat lung infections caused by Pseudomonas aeruginosa, binds to alginate present in biofilm extracellular matrix increasing its minimum inhibitory concentration (MIC). This work aimed to investigate the...

Antimalarial drugs have been suggested as promising scaffolds with anti-tubercular activities. In this work, we demonstrated, for the first time, the effectiveness of tafenoquine against mycobacteria. Firstly, tafenoquine inhibited the growth of Mycobacterium smegmatis and Mycobacterium tuberculosis with lower MICs values as compared to other antim...

The in vivo skin penetration by dermal microdialysis and the pharmacological efficacy of a chitosan hydrogel containing capsaicinoids-loaded nanocapsules (CHNCCaps) was evaluated in this study. Such gel has previously been proven to control capsaicinoids release and decrease the drugs side effects in humans. The nanocapsules containing capsaicinoid...

There are evidences about the involvement of systemic factors, such as brain-derived neurotrophic factor (BDNF), on functional exercise effects. Although aerobic exercise can impact circulating extracellular vesicles and particles (EVPs) cargo, other exercise modalities were not studied. Taken that BDNF and anti-inflammatory effects have been relat...

This study presents the development and validation of a fast and simple bioanalytical ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS) method intended for quantifying the anti-inflammatory candidate 5′-methoxynobiletin (5′-MeONB) in rat plasma. Standard of 5′-MeONB was purified from A. conyzoides extract by using preparati...

This study investigated plasma and brain disposition of quetiapine lipid core nanocapsules (QLNC) in naïve and schizophrenic (SCZ-like) rats and developed a semi-mechanistic model to describe changes in both compartments following administration of drug in solution (FQ) or nanoencapsulated. QLNC (1 mg/mL) presented 166 {plus minus} 39 nm, low polyd...

A versatile method was developed and validated for simultaneous determination of the monoamine neurotransmitters (MNT) dopamine (DA), 3-4-dyhydroxyphenilacetic acid (DOPAC), homovanilic acid (HVA), serotonin (5-HT) and 5-hydroxyindolacetic acid (5-HIAA) in rat brain microdialysate samples using high-performance liquid chromatography tandem mass spe...

Lipid core nanocapsules (LNC) have been extensively studied as a new treatment strategy to improve therapeutic effects of antipsychotic drugs. We investigated the efficacy of quetiapine LNCs (QLNCs) on the poly(i:c) model of schizophrenia in both male and female rats using the pre-pulse inhibition of startle response (PPI) test paradigm after evalu...

This report provides a brief description of the 2018 RedIF Congress that took place in Guadalajara (Mexico), on November 7‐9. The meeting aimed to foster modeling & simulation approaches for drug development, regulatory sciences and clinical application in Latin America. Organizations that cosponsored the meeting were: University of Guadalajara, In...

Purpose This work aimed to develop a population PK/PD tumor-in-host model able to describe etoposide effects on both tumor cells and host in Walker-256 tumor-bearing rats. Methods Etoposide was investigated on thirty-eight Wistar rats randomized in five arms: two groups of tumor-free animals receiving either placebo or etoposide (10 mg/kg bolus fo...

Ciprofloxacin (CIP) is indicated for clinical treatment of urinary and respiratory tract infections. Poor infection site penetration and consequent insufficient exposure to the antimicrobial agent may be the reason for some therapeutic failures. Ciprofloxacin is reported as a substrate for efflux transporters, such as P-glycoprotein, which could be...

Purpose: The present work aimed to evaluate the influence of experimental meningitis caused by C. neoformans on total plasma and free brain concentrations of fluconazole (FLC) in Wistar rats. Method: The infection was induced by the administration of 100 μL of inoculum (1.105 CFU) through the tail vein. Free drug in the brain was assessed by mic...

Antimicrobial prophylactic dosing of morbidly obese patients may differ from normal weighted individuals due to alterations on drug´s tissue distribution. Drug subcutaneous tissue distribution can be investigated by microdialysis patients and animals. The need of cefazolin prophylactic dose adjustment in obese patients remains under discussion. The...

Purpose: To determine the efficacious cefazolin prophylactic dose for bariatric surgery using free subcutaneous concentrations accessed by microdialysis after 2 g or 3 g i.v. bolus dosing to morbidly obese women and POPPK modeling. Methods: A POPPK model with variable plasma and subcutaneous tissue protein binding was developed to simultaneously...

Clindamycin is widely used in antimicrobial prophylaxis to prevent surgical site infections. Adequate subcutaneous free tissue concentrations should reach therapeutic levels, which have to be maintained throughout the surgical procedure for antibiotic prophylaxis to be efficient. A method was developed and validated using high performance liquid ch...

1. LASSBio-1736 ((E)-1-4(trifluoromethyl) benzylidene)-5-(2-4-dichlorozoyl) carbonylhydrazine) is proposed to be an oral cysteine protease leishmanicidal inhibitor. 2. This work aimed to investigate plasma pharmacokinetics, protein binding and tissue distribution of LASSBio-1736 in male Wistar rats. 3. LASSBio-1736 was administered to male Wistar r...

IQG-607 is an analog of isoniazid with anti-tuberculosis activity. This work describes the development and validation of an HPLC method to quantify pentacyano(isoniazid)ferrate(II) compound (IQG-607) and the pharmacokinetic studies of this compound in mice. The method showed linearity in the 0.5-50μg/mL concentration range (r=0.9992). Intra- and in...

Cyclooxygenase-2 (COX-2) isoform has a critical role in the development of pain. Inhibition of COX-2 in vitro serves as a biomarker for nonsteroidal anti-inflammatory drugs (NSAIDs). The NSAID concentrations yielding 80% COX-2 inhibition (IC80) correlate with therapeutic doses to achieve analgesia across multiple COX-2 inhibitors. However, there ar...

This work describes the development and validation of a quantitative and confirmatory method to determination of nine fluoroquinolones residues in poultry, bovine, swine and fish muscle using LC-MS/MS. Sample preparation was based in a fast solvent extraction with acetonitrile with 1% of formic acid followed by a low-temperature clean up procedure...

Biofilm formation plays an important role in the persistence of pulmonary infections, for example in cystic fibrosis patients. So far, little is known about antimicrobials lung disposition in biofilm-associated pneumonia. This study aimed to evaluate, by microdialysis, ciprofloxacin (CIP) penetration into the lungs of healthy and Pseudomonas aerugi...

To advance in the treatment of cryptococcal meningites is crucial to know the drug's free fraction that reaches the biophase. In the present study we applied the microdialysis (μD) as a tool to determine the free levels reached by voriconazole (VRC) in the brain of healthy and Cryptococcus neoformans infected rats. The infection was induced by the...

Background The inhibition of pyrimidine biosynthesis by blocking the dihydroorotate dehydrogenase (DHODH) activity, the prime target of leflunomide (LEF), has been proven to be an effective strategy for rheumatoid arthritis (RA) treatment. However, a considerable proportion of RA patients are refractory to LEF. Here, we investigated lapachol (LAP),...

We investigated the thermal, electrical and mechanical antinociceptive and physiological effects (heart rate, respiratory rate, arterial blood pressure, head height and abdominal auscultation score), and pharmacokinetics, of 0.5 mg/kg of the injectable formulation (ORAL) or nanoparticulated methadone (NANO) given orally, in six adult mares, using a...

The purpose of this study was to establish a population pharmacokinetic/pharmacodynamic (PK/PD) model linking etoposide free tumor and total plasma concentrations to the inhibition of solid tumor growth in rats. Walker-256 tumor cells were inoculated subcutaneously in the right flank of Wistar rats, which were randomly divided in control and two tr...

A bioanalytical LC-MS/MS method was developed and validated to determine tobramycin in plasma and lung microdialysate samples. Tobramycin was separated using a C18 column and a mobile phase consisting of water and acetonitrile, both with 10mM of heptafluorobutyric acid, eluted as gradient. Apramycin was used as internal standard (IS) for plasma sam...

Purpose: This study aimed to determine free etoposide (ETO) concentrations in two regions of Walker-256 (W256) solid tumor using microdialysis and to establish a population pharmacokinetic (popPK) model to describe simultaneously free tumor and total plasma concentrations. Methods: W256 tumor-bearing Wistar rats received ETO 10 or 20 mg/kg i.v....

Herbal preparations from Voacanga africana are used in West and Central African folk medicine and are also becoming increasingly popular as a legal high in Europe. Recently, the main alkaloid voacangine was found to be a potent human ether-à-go-go-related gene channel blocker in vitro. Blockage of this channel might imply possible cardiotoxicity. T...

A fast, simple, and sensitive reversed-phase high-performance liquid chromatography (RP-HPLC) method has been developed and fully validated for the determination of moxifloxacin (MXF) in rat plasma. MXF and gatifloxacin (internal standard, I.S.) were extracted from plasma by single-step protein precipitation with acidified acetonitrile. Chromatogra...

This work aimed to develop nanocapsules (NC) coated with polysorbate 80 (P80), cationic chitosan (CS) or polyethylene glycol (PEG) using clozapine (CZP) as the drug model. The zeta potential, pH and encapsulation efficiency were directly affected by the CS coating. Using the bag dialysis method, the in vitro CZP release from CS-coated nanocapsules...

A simple, rapid and sensitive method for confirmatory and quantitative purposes using liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS) was developed and validated for determination of chloramphenicol, thiamphenicol, florfenicol and its metabolite, florfenicol amine, in poultry, swine, bovine and fish muscle. Sam...

Lipid-core nanocapsules (LCN) have been proposed as drug carriers to improve brain delivery by modulating drug pharmacokinetics (PK). However, it is not clear whether the LCN carry the drug through the BBB or increase free drug penetration due to changes in the barrier permeability. Quetiapine (QTP) penetration to the brain is mediated by influx tr...

An accurate and reliable LC-MS/MS assay was firstly developed and validated for quantitative determination of a new antimalarial prototype drug, 3β-hydroxyurs-12-en-28-oic acid (LAFIS 01), in rat plasma. Dexamethasone was employed as internal standard. Simple protein precipitation by acetonitrile for the sample preparation was used. Effective separ...

Levofloxacin (LEV) is a broad spectrum fluoroquinolone used to treat pneumonia, urinary tract infections, chronic bacterial bronchitis and prostatitis. Efflux transporters, primarily P-glycoprotein (P-gp), are involved in LEV's tissue penetration. In the present work LEV free lung and prostate interstitial space fluid (ISF) concentrations were eval...

This study aims to investigate the changes in plasma pharmacokinetics and liver and brain distribution of quetiapine (QTP) due to its encapsulation into a polymeric nanocarrier. For this reason a bioanalytical method was developed and validated in order to quantify QTP in plasma, liver and brain tissue samples. The method was linear over the concen...

The bark of Voacanga africana Stapf ex Scott Elliot and related species is not only used in African folk medicine, but also as legal high with increasing popularity in Europe. Voacangine (1), its major iboga-type alkaloid, was recently identified as potent hERG channel blocker in vitro which might point towards possible cardiotoxicity [1]. Since th...

In this study, a sensitive HPLC-UV assay was developed and validated for the determination of LASSBio-1736 in rat plasma using sodium diclofenac as internal standard (IS). Liquid-liquid extraction using acetonitrile was employed to extract LASSBio-1736 and IS from 100 uL of plasma previously basified with NaOH 0.1 N. Chromatographic separation was...

Quetiapine is an atypical antipsychotic used to treat schizophrenia. However, despite great interest for its chronic therapeutic use, quetiapine has some important side effects such as weight gain induction. The development of a quetiapine nanocarrier can potentially target the drug into central nervous system, resulting in a reduction of systemic...

A selective and sensitive UHPLC-MS/MS bioanalytical method to determine PT-31, an analgesic drug candidate, in rat plasma was developed and validated. Analyses were performed in a UHPLC-MS/MS system equipped with an electrospray ionization interface operating in the positive ionization mode using a C18 reversed-phase column with a mobile phase of w...

This study aimed to investigate the pharmacokinetics, tissue distribution and antipsychotic activity of olanzapine administered as free drug (OLA-FREE) or loaded into lipid-core nanocapsules (OLA-LNC). OLA-LNC were successfully developed with a particle size of 142 ± 4 nm and a zeta potential of –19.6 ± 0.6 mV. Pharmacokinetics and tissue distribut...

Chronic Bacterial prostatitis treatment consists of broad-spectrum antibiotic therapy for long periods of time. Drug penetration into the prostate makes the treatment a challenged. Ciprofloxacin is one of the most prescribed drugs for this treatment. A liquid chromatography with fluorescence detection method was developed and validated for determin...

A fast, simple, and sensitive reversed-phase high-performance liquid chromatography (RP-HPLC) method has been developed and fully validated for the determination of moxifloxacin (MXF) in rat plasma. MXF and gatifloxacin (internal standard, I.S.) were extracted from plasma by single-step protein precipitation with acidified acetonitrile. Chromatogra...

The aim of this paper was to analyze the impact of anesthesia induced by urethane on pharmacokinetics (PK) parameters of fluconazole (FCZ), mostly eliminated via renal excretion and voriconazole (VRC), eliminated mainly by hepatic metabolism. FCZ and VRC PK were investigated after administration of 10 mg/kg i.v. and 5 mg/kg i.v. doses to awake and...

A novel LC-MS/MS method was developed for the quantification of vildagliptin in an aqueous matrix. The method was successfully validated, meeting all the requisites of US Food and Drug Administration guide for a bioanalytical method. The developed method presented a limit of quantification of 10 ng/mL and the range of concentration achieved was 10-...

The in vivo absorption of didanosine was studied, focusing on the performance of a novel pharmaceutical formulation for didanosine, composed of chitosan granules containing didanosine incorporated in chitosan microspheres. This novel formulation is aimed at oral administration in AIDS therapy. The experimental results in male adult dogs showed cont...

A rapid and highly sensitive method by LC-MS/MS was developed and validated for the quantification of an antimalarial candidate (LAFIS10) in rat plasma using dexamethasone as internal standard (IS). The chromatographic separation was performed with a Poroshell 120 EC-C18 column. The mobile phase consisted of water (A) and acetonitrile (B), both con...

A simple and sensitive bioanalytical method was developed and validated for determination of etoposide in plasma and microdialysis samples of Walker-256 tumor-bearing rats. A microdialysis probe was implanted in the center of a subcutaneous tumor and Ringer's solution was used as perfusion medium. Chromatographic separation was conducted on a Shima...

The drug-transporting proteins can affect the pharmacokinetics and pharmacodymanics of many drugs, resulting in an erratic and unpredictable pharmacological response. The Caco-2 monolayer is routinely applied to investigate the carrier-mediated transport of drugs. Therefore, the selection of a marker compound able to characterize the activity of su...

Moxifloxacin is reported to have increased distribution into the prostate compared with older fluoroquinolones such as norfloxacin and ciprofloxacin, being able to reach tissue-to-plasma concentration ratios greater than unity. However, most of these studies use tissue homogenates derived from biopsy samples, which can lead to overestimation of fre...

A simple HPLC/UV method was developed for the determination of the anticancer candidate LaSOM 65 in rat plasma. Samples were cleaned by protein precipitation with acetonitrile (recovery > 95%), after which they were subjected to chromatography under the isocratic elution of an acetonitrile: water (45: 55, v/v) solution with detection at 303 nm. The...

Levofloxacin is a broad-spectrum fluoroquinolone used in the treatment of both acute and chronic bacterial prostatitis. Currently, the treatment of bacterial prostatitis is still difficult, especially due to the poor distribution of many antimicrobials into the prostate, thus preventing the drug to reach effective interstitial concentrations at the...

Diagnostic and therapeutic decisions in medical practice are still generally based on blood concentrations of drugs and/or biomolecules despite the knowledge that biochemical events and pharmacological effects usually take place in tissue rather than in the bloodstream. Microdialysis is a semi-invasive technique that is able to measure concentratio...

In spite of different methods reported in the literature to determine olanzapine in biological fluids, all of them used high volumes of plasma. Therefore, the purpose of this paper was to develop an LC-MS/MS method using small plasma volume (0.1 mL) to apply in a preclinical pharmacokinetic investigation. The method was linear over the concentratio...

Abstract The aim of this study was to develop innovative nanosystems with isopropyl myristate as the oil core of self-assembly nanovesicles constituted of chitosan and lecithin using a 2(3) factorial design. The factors analyzed were chitosan (X1, levels 4 and 8 mg/ml), oil (X2, levels 10 and 20 mg/ml) and lecithin (X3, levels 4 and 8 mg/ml). The r...

Abstract 1. The present work investigated the pharmacokinetic and tissue distribution as well as acute toxicity of a new chemical entity (NCE), the anticancer candidate LaSOM 65 in Wistar rats. 2. LaSOM 65 pharmacokinetics was investigated after intravenous (i.v., 1 mg/kg) and oral (p.o., 10 and 30 mg/kg) dosing. Tissue distribution was assessed af...

An isocratic, accurate, simple and precise high performance liquid chromatographic method was validated for the determination of gatifloxacin and levofloxacin in Todd-Hewitt broth. A simple one step protein precipitation extraction with acetonitrile was employed. Separation using a C18 column and a flow rate of 1.0 mL/min was performed. The mobile...

A liquid chromatography method has been established for the reliable determination of unbound gemifloxacin concentrations in kidney, lung and liver microdialysates of rats. Microdialysis probes were inserted into tissues of rats, and then dialysates were collected at regular time intervals after intravenous administration of gemifloxacin (40mgkg(-1...

Benzaldehyde semicarbazone (BS) has presented positive results in several pharmacological models, including anticonvulsivant and anti-inflammatory models. The present study evaluated the preclinical toxicity (acute and subchronic), as well as the toxicokinetic and gastroprotective effects of BS against ethanol lesions. Oral doses of 300 and 2000 mg...

In the present work it was developed a disseminated candidiasis infection model to Wistar rats. The conditions of immunosuppression and the infecting ability of three species of Candida prevalent in nosocomial infections were tested for count of viable cells present in the kidneys and degree of tissue injury after 2 or 7 days of infection. Immunoco...

The aims of this study were to evaluate free levels of fluconazole (FCZ) in the kidneys of healthy and Candida albicans-infected Wistar rats using microdialysis and to establish the relationship between free renal and total plasma levels under both conditions. Microdialysis recovery rates were determined in vitro by dialysis, and retrodialysis reco...

The naturally occurring 1,4-naphtoquinone, lapachol, has been widely studied due to its diverse biological activities, of which the anti-cancer activity has taken a prominent position. Even though lapachol and other reported quinone derivatives are known as constituents in extracts/products used in traditional medicine, only few data are available...

The cutaneous penetration of isotretinoin-loaded poly(epsilon-caprolactone) nanocapsules (GEL-NCISO) was compared to that of free isotretinoin (GEL-FREE) incorporated in hydrogels by tape stripping in excised human and pig skin. The physicochemical stability of isotretinoin-loaded nanocapsules and a nanoemulsion (used as a control) was evaluated us...

An LC method was developed and validated in order to quantify the saponin purified fraction named QB-90 obtained from the aqueous extracts of Quillaja brasiliensis leaves. Previously, QB-90 was shown to be active as adjuvant in an experimental vaccine for herpesvirus bovine type 1 in mice. The analysis was performed using an RP-8 column with aceton...

The aim of this paper is to develop and validate an HPLC method to investigate the tissue distribution of gemifloxacin (GEM) in rats following intravenous administration and compare the penetration of this drug in different tissues undergoing normobaric and hyperbaric oxygen (HBO) exposure. The chromatographic conditions consisted of a C18 column a...

This work aimed to investigate plasma pharmacokinetics and tissue distribution of a new acridine derivative 5-acridin-9-ylmethylene-3-(4-methyl-benzyl)-thiazolidine-2,4-dione (AC04) and its 1-oxo-AC04 metabolite disposition in Wistar rats. After a single AC04 1.5 mg/kg intravenous (i.v.) bolus dose, blood samples were taken up to 120 h. Plasma samp...

Didanosine is an effective antiviral drug in untreated and antiretroviral therapy-experienced patients with Human Immunodeficiency Virus (HIV). An automated system using on-line solid extraction and High Performance Liquid Chromatography (HPLC) with ultraviolet (UV) detection was developed and validated for pharmacokinetic analysis of didanosine in...

A highly sensitive, rapid assay method has been developed and validated for the quantification of clozapine in rat plasma using LC-MS/MS. The extraction process involved plasma protein precipitation with acetonitrile and elution with a mobile phase constituted by acetonitrile and acidic water (80/20), at 0.8 mL/min flow rate (split 1:3). Chromatogr...

A reliable, simple and sensitive liquid chromatography-electrospray ionisation-tandem mass spectrometry (LC-ESI-MS/MS) confirmation method has been developed for chloramphenicol (CAP) determination in honey, fish and prawns. For honey, samples were extracted with ethyl acetate, an aliquot was evaporated to dryness and re-dissolved in mobile phase....

A simple, accurate and precise high-performance liquid chromatographic method with fluorescence detection was developed and validated for the determination of gemifloxacin (GEM) in rat plasma using furosemide as internal standard (I.S.). Plasma samples were pretreated by direct deproteinization and all samples and standard solutions were chromatogr...

The aim of this work was to compare the pharmacological properties of levofloxacin and gatifloxacin against Streptococcus pneumoniae by pharmacokinetic/pharmacodynamic (PK/PD) modelling of the time-kill curves employing an E(max) model. An in vitro infection model was used to simulate free pulmonary fluctuating concentrations expected after multipl...

A fast, sensitive, and specific LC–MS–MS method for determination of quinine (QN) and doxycycline (DOX) in rat plasma has been developed and validated. QN, DOX, and cimetidine (internal standard, IS) were extracted from the plasma by protein precipitation. The compounds were separated on a C18 column with methanol–0.1% aqueous formic acid 70:30 (v/...

A liquid chromatography-tandem mass spectrometry method was developed for accurate quantification of the acridinic anticancer candidate AC04 (5-acridin-9-ylmethylene-3-(4-methyl-benzyl)-thiazolidine-2,4-dione) in rat plasma viewing the drug's pre-clinical pharmacokinetic investigation. The sample purification was performed by protein precipitation...

A modified E(max)-pharmacokinetic-pharmacodynamic (PK-PD) model was previously proposed in literature for describing the antimicrobial activity of β-lactam antibiotics based on in vitro experiments. However, bacteria behave differently in vitro and in vivo. Thus, the aims of this study were to model the killing effect of piperacillin (PIP) against...

A simple and sensitive HPLC method was validated for assessment of in vitro and in vivo recovery of gatifloxacin using microdialysis. The validation parameters of linearity, precision, accuracy and limit of detection were studied as well as stability. Correlation coefficient (r 2) obtained was > 0.999 for all calibration curves (20 - 600 ng.mL -1)....

Poisoning by drugs is rather frequent in Brazil in the age range of 0 to 14 years. Intoxication by valproic acid (VA) stands out because of an increase in its spectrum of clinical use; hepatotoxicity is an important reaction that can be triggered by high concentrations of this drug and there is a high incidence of toxic events in children. Therefor...

the determination of oral bioavailability of drugs which follow nonlinear pharmacokinetics is difficult and few methods are available. In this work, an alternative approach to determine oral bioavailability of voriconazole (VRC), used as a model drug, is presented. VRC pharmacokinetics was investigated in Wistar rats after p.o. (40 mg/kg) and i.v....

A rapid, sensitive, and simple HPLC/MS/MS method was developed and validated for the determination of (5Z,E)-3-[2-(4-chlorophenyl)-2-oxoethyl]-5-(1H-indol-3-ylmethylene)-thiazolidine-2, 4-dione (PG15) in rat plasma using chlortalidone as an internal standard (IS). Analyses were performed using a C18 column and isocratic elution with acetonitrile-wa...

The study aimed to investigate the pharmacokinetics and tissue distribution of the benzaldehyde semicarbazone (BS) a potential antiepileptic drug, administered as a free drug or complexed beta-cyclodextrin (BS/beta-CD). Free BS and BS/beta-CD were administered to male Wistar rats as a 10mg/kg intravenous bolus dose. For the oral route, 50mg/kg and...

The present study was designed to investigate the effect of a single purple grape juice administration on cyclosporin A (CyA) oral bioavailability in healthy volunteers. The study followed a two-period crossover design, where the volunteers were randomly assigned to receive 200-mg CyA soft-gelatin capsules with 200 mL of either purple grape juice o...

A simple, rapid, and sensitive high performance liquid chromatographic method using UV detection (HPLC-UV) for the determination of benzaldehyde semicarbazone (BS) in rat plasma was developed and validated using sodium diclofenac as an internal standard (IS). Analyses were performed on an HPLC system using a C18 column and isocratic elution with mo...