pharmcokinetic

Older adults frequently have many systemic diseases that require treatment with multiple drugs, and thus anticholinergic adverse effect by polypharmacy is a significant concern in the management of older adults. The accuracy of the anticholinergic burden rating may be increased by considering pharmacokinetic and pharmacodynamic factors such as biophase drug concentrations, the pharmacologically active metabolites formed after drug administration, and muscarinic receptor-mediated effects. Therefore, a pharmacological evidence-based burden scale that considers pharmacokinetic and pharmacodynamic factors is expected to be a more optimal tool for precisely assessing the anticholinergic burden, specifically risk reductions in anticholinergic adverse events in the poly-medicated elderly...

Escherichia albertii is an emerging, enteric pathogen of significance. It was first isolated in 2003 from a pediatric diarrheal sample from Bangladesh. In this study, a comprehensive in silico strategy was followed to first list out antibiotic-resistant genes from core, accessory and unique genome fractions of 95 available genomes of E. albertii . Then, 56 drug targets were identified from the core essential genome. Finally, ZipA, an essential cell division protein that stabilizes the FtsZ protofilaments by cross-linking them and serves as a cytoplasmic membrane anchor for the Z ring, was selected for further downstream processing...

Aim: We aimed to assess the effect of a functional polymorphism of CYP3A5 on lumefantrine pharmacokinetics. Patients & methods: Sixty-nine women diagnosed with malaria received standard doses of artemether-lumefantrine. Concentration-time data for lumefantrine and genotyping data were obtained for each participant. Pharmacokinetic-genotype associative relationships were assessed using linear regressions, Mann-Whitney U-test or Kruskal-Wallis statistics. Results: Average age and weight (standard deviation) of the patients were 33 (6...

BACKGROUND: In developing countries, malnutrition remains a common clinical syndrome at antiretroviral treatment (ART) initiation. Physiologic changes because of malnutrition and during nutritional recovery could affect the pharmacokinetics of antiretroviral drugs. METHODS: HIV-infected children admitted with severe acute malnutrition were randomized to early or delayed initiation of lopinavir (LPV)/ritonavir, abacavir and lamivudine using World Health Organization weight band dosage charts...

Nanotheranostics is a rapidly growing field combining disease diagnosis and therapy, which ultimately may add in the development of 'personalized medicine'. Here, we designed and developed bioresponsive and fluorescent hyaluronic acid-iodixanol nanogels (HAI-NGs) for targeted X-ray computed tomography (CT) imaging and chemotherapy of MCF-7 human breast tumors. HAI-NGs were obtained with a small size of ca. 90nm, bright green fluoresence and high serum stability from hyaluronic acid-cystamine-tetrazole and reductively degradable polyiodixanol-methacrylate via nanoprecipitation and a photo-click crosslinking reaction...

OBJECTIVE: To determine the effects of different formulations of Banxia Xiexin Decoction ( , BXD) on the pharmacokinetics of baicalin (BAL) in mice. METHODS: Pungent, bitter, and sweet components of BXD (totaling 7 Chinese herbs) were formulated into the following groups: K (bitter herbs), XK (pungent and bitter herbs), KG (bitter and sweet herbs), and BXD (all 7 herbs) groups. These different formulations were administered intragastrically in mice, and blood was collected via the tail vein for continuous monitoring...

A direct large volume injection high-performance liquid chromatography (HPLC) method with homemade restricted-access media (RAM) pre-column and combined with a column-switching valve was established and developed for determination rifampicin (RIP) in rat plasma. The rat plasma samples (100 μL) were injected directly onto pre-column, where RIP was retained and pre-concentrated, while proteins were washed to waste using a methanol-water (5:95) as the mobile phase at a flow rate of 1 mL/min. Then, by rotation of the switching valve at 5 min, the RIP were eluted from the pre-column and transferred to an Luna C18 analytical column by the chromatographic mobile phase consisting of methanol-acetonitrile-10 mm ammonium format (60:5:35) at a flow rate of 1 mL/min...

Reports from human case studies indicate a half-life for inorganic mercury in the brain in the order of years-contradicting older radioisotope studies that estimated half-lives in the order of weeks to months in duration. This study systematically reviews available evidence on the retention time of inorganic mercury in humans and primates to better understand this conflicting evidence. A broad search strategy was used to capture 16,539 abstracts on the Pubmed database. Abstracts were screened to include only study types containing relevant information...

Children account for between 15 - 20 % of all imported malaria cases worldwide. Immigrant children visiting their families in the country of origin in sub-Saharan Africa are at highest risk. Prevention of malaria in children who travel to endemic areas is guided by the ABCD principles - Awareness of risk, Bite prevention, Chemoprophylaxis for high risk areas and rapid Diagnosis and treatment when malaria is suspected. The use of anti-malarial medication in small children is hampered by a paucity of dosage, pharmcokinetic and tolerability data...

Dovitinib is an oral multitargeted kinase inhibitor with potent activity against receptors for vascular endothelial growth factor, platelet-derived growth factor, and basic fibroblast growth factor. Initial phase 1 to 2 studies of dovitinib using a continuous daily dosing schedule has shown that dovitinib exhibits a prolonged and overproportional increase in dose and exposure relationship above 400 mg/d. To address this, intermittent dosing schedules were explored using a model-based approach. A semi-mechanistic population pharmcokinetic/pharmacodynamic (PD) model was developed from 4 dovitinib phase 1 studies with daily dosing schedules...

AIM: A key role of renal nurses is the correct and safe administration of immunosuppressive drug therapy (ImmRx) to kidney transplant recipients. The authors sought to examine the knowledge and competency of ImmRx in kidney transplant patients and whether an annual kidney transplant nurse education programme had any beneficial effects. METHODS: The study population was comprised of 63.2% (n=50/79) of all nurses from renal wards (ward A (n=17/35), ward B (n=21/32)) and 12 nurses from a high-dependency urology ward (ward C (n=12))...

Fexofenadine (FEX) has been extensively used for therapeutic benefits after the market withdrawal of terfenadine. Recently, the popularity of FEX has emerged owing to its unique disposition via drug transporters and, hence, it has been used as a model probe for both in vitro and in vivo investigations to understand mechanistic aspects of drug-drug interactions (DDI). Going hand in hand with the increased use of FEX in therapy and research, numerous bioanalytical methods for FEX have been published. The various published bioanalytical methods for FEX are collated in this review to provide a comprehensive information on extraction methodology, assay conditions, chromatography and detection systems...

Dovitinib is an oral multitargeted kinase inhibitor with potent activity against receptors for vascular endothelial growth factor, platelet-derived growth factor, and basic fibroblast growth factor. Initial phase 1 to 2 studies of dovitinib using a continuous daily dosing schedule has shown that dovitinib exhibits a prolonged and overproportional increase in dose and exposure relationship above 400 mg/d. To address this, intermittent dosing schedules were explored using a model-based approach. A semi-mechanistic population pharmcokinetic/pharmacodynamic (PD) model was developed from 4 dovitinib phase 1 studies with daily dosing schedules...

The DNA gyrase inhibitor cyclothialidine had been shown to be a valuable lead structure for the discovery of new antibacterial classes able to overcome bacterial resistance to clinically used drugs. Bicyclic lactone derivatives containing in their 12-14-membered ring a thioamide functionality were reported previously to exhibit potent antibacterial activity against gram-positive bacteria. Moderate in vivo efficacy, however, was demonstrated only for derivatives bearing hydrophilic substituents, which were found to have a favorable impact on pharmcokinetics, and to reduce metabolic degradation, in particular glucuronidation...

Rituximab efficacy in cancer therapy depends in part on induction of complement-dependent cytotoxicity (CDC). Human CD59 (hCD59) is a key complement regulatory protein that restricts the formation of the membrane attack complex, thereby inhibiting induction of CDC. hCD59 is highly expressed in B-cell non-Hodgkin's lymphoma (NHL), and upregulation of hCD59 is an important determinant of the sensitivity of NHL cells to rituximab treatment. Here, we report that the potent hCD59 inhibitor rILYd4 enhances CDC in vitro and in vivo, thereby sensitizing rituximab-resistant lymphoma cells and primary chronic lymphocytic leukemia cells (CLL) to rituximab treatment...

A specific and automated method was developed to quantify the anticonvulsants gabapentin, pregabalin and vigabatrin simultaneously in human serum. Samples were prepared with a protein precipitation. The hydrophilic interaction chromatography (HILIC) with a mobile phase gradient was used to divide off ions of the matrix and for separation of the analytes. Four different HILIC-columns and two different column temperatures were tested. The Tosoh-Amid column gave the best results: single small peaks. The anticonvulsants were detected in the multiple reaction monitoring mode (MRM) with ESI-MS-MS...

Glucosamine is an amino sugar involved in the biosynthesis of glycosylated proteins and lipids. Recently, with increased public interest in natural products medicine, glucosamine has been widely used to treat osteoarthritis, even though demonstrations of its actual efficacy remain relatively unknown. Information related to the pharmcokinetics of glucosamine is sparse. A recent analytical method published used 13C-glucosamine as an internal standard to analyse study samples. The method lacked accuracy owing to an important natural isotopic contribution of glucosamine to 13C-glucosamine ion abundance...

A specific and automated method was developed to quantitate the aminoglycosides amikacin, gentamicin, kanamycin, neomycin, paromomycin, and tobramycin simultaneously in human serum. Samples were prepared with an automated solid phase extraction (SPE). The hydrophilic interaction chromatography (HILIC) was used for separation of analytes from endogenous compounds and baseline separation. The aminoglycosides were detected with electrospray ionisation tandem mass spectrometry (ESI-MS-MS). Using a volume of 500 microl biological sample the lower limits of quantification were 100 ng/ml or better...

This study investigated the pharmcokinetics, efficacy, and safety of the fentanyl transdermal therapeutic system (TTS) in horses in which there was an inadequate analgesic response to nonsteroidal anti-inflammatory drugs (NSAIDs) alone. Nine horses with pain that was refractory to therapeutic doses of phenylbutazone (n = 3) or flunixin meglumine (n = 6) subsequently also received between 39 and 110 microg/kg of transdermal fentanyl. Blood samples were collected at 0, 1, 2, 3, 4, 5, 6, 12, 24, 36, 48, 60, and 72 hours after patch application, and a radioimmunoassay was used to determine serum fentanyl concentrations...

A specific, and automated method was developed to quantitate neomycin in human serum. Samples were prepared with an automated solid phase extraction (SPE). The hydrophilic interaction chromatography (HILIC) was used for additional sample cleanup and baseline separation. The analyte neomycin was detected with electrospray ionisation tandem mass spectrometry (ESI-MS-MS). Using a volume of 500 microl biological sample the lower limit of quantification was 100 ng/ml. The described HILIC-MS-MS method is suitable for clinical and pharmcokinetical investigations of neomycin...