Current Issue : January - March Volume : 2017 Issue Number : 1 Articles : 7 Articles
A simple, precise, rapid and sensitive bioanalytical RP-HPLC method was developed for estimation of lurasidone HCl in rat plasma. The work carried out using Purospher® STAR Hibar® 250 mm C18 (4.6 mm × 25 cm, packed with 5m particles) column equipped with Shimadzu LC-2010 CHT HPLC system with mobile phase containing acetonitrile: methanol: 0.01M sodium phosphate monobasic buffer (pH 4) in the ratio 60:30:10 v/v (1.2 ml/min) and detection wavelength 230 nm. The retention time of lurasidone HCl was found to be 7.81 min. The developed bioanalytical method was found to be linear in concentration range of 2.27-13.63 ng/µl (R2 =0.9778) with LLOQ of 2.27 ng/µl and ULOQ of 13.63 ng/µl. The precision study revealed that the percentage cumulative variation was within acceptable limit and accuracy study showed the value of mean percent recovery between 87.06-103.39 %. The lurasidone HCl was stable in rat plasma at different storage conditions. The validation parameters of the method met the acceptance criteria. Sufficient stability at LQC and HQC was shown to allow for completion of sample analysis in clinical trials. From the results, it was concluded that developed bioanalytical method can be used for routine analysis of lurasidone HCl....
Background: Blood biomarkers of neurovascular damage are used clinically to diagnose the presence severity or\nabsence of neurological diseases, but data interpretation is confounded by a limited understanding of their dependence\non variables other than the disease condition itself. These include half-life in blood, molecular weight, and\nmarker-specific biophysical properties, as well as the effects of glomerular filtration, age, gender, and ethnicity. To\nstudy these factors, and to provide a method for markersââ?¬â?¢ analyses, we developed a kinetic model that allows the\nintegrated interpretation of these properties.\nMethods: The pharmacokinetic behaviors of S100B (monomer and homodimer), Glial Fibrillary Acidic Protein and\nUbiquitin C-Terminal Hydrolase L1 were modeled using relevant chemical and physical properties; modeling results\nwere validated by comparison with data obtained from healthy subjects or individuals affected by neurological diseases.\nBrain imaging data were used to model passage of biomarkers across the bloodââ?¬â??brain barrier.\nResults: Our results show the following: (1) changes in biomarker serum levels due to age or disease progression are\naccounted for by differences in kidney filtration; (2) a significant change in the brain-to-blood volumetric ratio, which\nis characteristic of infant and adult development, contributes to variation in blood concentration of biomarkers; (3)\nthe effects of extracranial contribution at steady-state are predicted in our model to be less important than suspected,\nwhile the contribution of bloodââ?¬â??brain barrier disruption is confirmed as a significant factor in controlling markersââ?¬â?¢\nappearance in blood, where the biomarkers are typically detected; (4) the contribution of skin to the marker S100B\nblood levels depends on a direct correlation with pigmentation and not ethnicity; the contribution of extracranial\nsources for other markers requires further investigation.\nConclusions: We developed a multi-compartment, pharmacokinetic model that integrates the biophysical properties\nof a given brain molecule and predicts its time-dependent concentration in blood, for populations of varying\nphysical and anatomical characteristics. This model emphasizes the importance of the bloodââ?¬â??brain barrier as a gatekeeper\nfor markersââ?¬â?¢ blood appearance and, ultimately, for rational clinical use of peripherally-detected brain protein....
Previous study suggested that low body weight was one of the risk factors of thrombocytopenia\ninduced by linezolid in non-hemodialysis patients. However, there have\nbeen little investigations for the linezolid-induced thrombocytopenia in hemodialysis\npatients. This study was to evaluate the association between several factors of body\nsize descriptors and thrombocytopenia in hemodialysis-patients. No factor of body\nsize descriptors showed significant correlation with linezolid-induced thrombocytopenia\n(patients with thrombocytopenia vs patients without thrombocytopenia: body\nweight; 60.0 kg vs 55.3 kg, p = 0.82: body mass indices; 21.1 kg/m2 vs 21.2 mg/m2, p =\n0.44: ideal body weight; 61.2 kg vs 59.5 kg, p = 0.21: lean body weight; 50.1 kg vs 45.7\nkg, p = 0.64: dosage amount; 20.0 mg/kg vs 21.7 mg/kg, p = 0.74: body surface area;\n1.65 m2 vs 1.54 m2, p = 0.43). There were not significant differences in the body size\ndescriptors between linezolid therapy for more than 14 days and for less than 13 days\n(more than 14 days vs less than 13 days: body weight; 53.5 kg vs 56.8 kg, p = 0.75:\nbody mass indices; 20.9 kg/m2 vs 21.1 mg/m2, p = 0.47: ideal body weight; 60.3 kg vs\n59.9 kg, p = 0.17: lean body weight; 44.3 kg vs 47.7 kg, p = 0.56: dosage amount; 22.4\nmg/kg vs 21.1 mg/kg, p = 0.67: body surface area; 1.51 m2 vs 1.59 m2, p = 0.37). Our\ndata suggested that dosage adjustment of linezolid based on body weight was not\nrecommended in hemodialysis-patients....
Background: Glycated haemoglobin (HbA1c) is an important outcome measure in diabetes clinical trials. For\nmulticentre designs, HbA1c can be measured locally at participating centres or by sending blood samples to a\ncentral laboratory. This study analyses the agreement between local and central measurements, using 1-year follow-up\ndata collected in a multicentre randomised controlled trial (RCT) of newly diagnosed children with type I diabetes.\nMethods: HbA1c measurements were routinely analysed both locally and centrally at baseline and then at 3, 6, 9 and\n12 months and the data reported in mmol/mol. Agreement was assessed by calculating the bias and 95 % limits of\nagreement, using the Bland-Altman analysis method. A predetermined benchmark for clinically acceptable margin of\nerror between measurements was subjectively set as Ã?±10 % for HbA1c. The percentage of pairs of measurements that\nwere classified as clinically acceptable was calculated. Descriptive statistics were used to examine the agreement within\ncentres. Treatment group was not considered.\nResults: Five hundred and ninety pairs of measurement, representing 255 children and 15 trial centres across four\nfollow-up time points, were compared. There was no significant bias: local measurements were an average of 0.\n16 mmol/mol (SD = 4.5, 95 % CI âË?â??0.2 to 0.5) higher than central. The 95 % limits of agreement were âË?â??8.6 to 9.\n0 mmol/mol (local minus central). Eighty percent of local measurements were within Ã?±10 % of corresponding\ncentral measurements. Some trial centres were more varied in the differences observed between local and\ncentral measurements: IQRs ranging from 3 to 9 mmol/mol; none indicated systematic bias.\nConclusions: Variation in agreement between HbA1c measurements was greater than had been expected\nalthough no overall bias was detected and standard deviations were similar. Discrepancies were present across all\nparticipating centres. These findings have implications for the comparison of standards of clinical care between\ncentres, the design of future multicentre RCTs and existing quality assurance processes for HbA1c measurements.\nWe recommend that centralised HbA1c measurement is preferable in the multicentre clinical trial setting....
for short procedures. In orally premedicated patients we obtained midazolam plasma concentrations at the end of\nsurgical procedures and compared those to concentrations at anesthesia induction.\nMethods: The study was conducted prospectively with consent of the local ethics committee (Ethikkomission\nKanton Thurgau, Switzerland) and carried out with written informed consent of each patient. Female patients aged\n20 to 60 years undergoing elective procedures with general anesthesia were included, and were divided in two\ngroups according to the planned surgical time: group S (<30 min) and group L (90ââ?¬â??120 min), respectively. All patients\nreceived 7.5 mg Midazolam po as premedication. Blood samples were drawn at anesthesia induction, and at the end\nof surgery. Data were compared with t-test (independent samples; significance level p <0.05).\nResults: Twenty-five patients per group were included. Four patients were excluded from analysis, since midazolam\nwas not detectable in any samples. Time of premedication to the 1st blood sample was not statistically different between\ngroups, neither were Midazolam plasma levels at this time point (p = 0.94). None of the patients from group L (n = 24),\nbut five patients in group S (n = 22) did have a higher plasma level of Midazolam at the end of the case compared to\nthe beginning.\nConclusions: The elimination half-life of oral Midazolam can lead to higher plasma levels at the end of a short\nprocedure compared to those at induction of anesthesia....
Background: The new microcapillary and fluorescence-based EC IVD-qualified Museââ??¢ Auto CD4/CD4% singleplatform\nassay (EMD Millipore Corporation, Merck Life Sciences, KGaA, Darmstadt, Germany) for CD4 T cell numeration\nin absolute number and in percentage was evaluated using Central African patientsââ?¬â?¢ samples compared against the\nreference EC IVD-qualified BD FACSCount (Bectonââ?¬â??Dickinson, USA) flow cytometer.\nMethods: EDTA-blood samples from 124 adults, 10 adolescents, 13 children and 3 infants were tested in parallel at 2\nreference laboratories in Bangui.\nResults: The Museââ??¢ technique was highly reproducible, with low intra- and inter-run variabilities less than 15%. CD4\nT cell counts of Museââ??¢ and BD FACSCount in absolute number and percentage were highly correlated (r2 = 0.99 and\n0.98, respectively). The mean absolute bias between Museââ??¢ and BD FACSCount cells in absolute number and percentage\nwere âË?â??5.91 cells/Ã?¼l (95% CI âË?â??20.90 to 9.08) with limits of agreement from âË?â??77.50 to 202.40 cells/Ã?¼l, and +1.69\n...
Background: This study aimed to develop a simultaneous determination method for tramadol and its\ndesmethylates in human plasma using isocratic liquid chromatography coupled to tandem mass spectrometry and\nto validate it for pharmacokinetic evaluation in patients with cancer pain or non-cancer pain.\nMethods: The pretreatments for human plasma involved protein precipitation using acetonitrile and methanol\nunder basic conditions. Tramadol, O-desmethylate, N-desmethylate, and N,O-didesmethylate were separated on an\noctadecylsilyl column filled with 3-Ã?¼m particles using isocratic mixture of methanol and 0.15 % formic acid in water\n(35:65, v/v). The mass spectrometer was run in positive ion multiple reaction monitoring mode. This method was\napplied to the determination of plasma samples in patients treated with oral tramadol.\nResults: The chromatographic total run time was 10 min. The calibration curves in human plasma of\ntramadol, O-desmethylate, N-desmethylate, and N,O-didesmethylate were linear over the concentration ranges\nof 12.5ââ?¬â??1600, 2.5ââ?¬â??320, 2.5ââ?¬â??320, and 2.5ââ?¬â??320 ng/mL, respectively. The lower limits of quantitation of tramadol\nand its desmethylates in human plasma were 12.5 and 2.5 ng/mL. Their extraction recoveries were 85.5ââ?¬â??106.\n3 %. The intra-day and inter-day precisions and accuracies were 1.6ââ?¬â??10.2 % and 89.2ââ?¬â??106.2 % for all analytes.\nThe plasma concentration ranges of tramadol, O-desmethylate, N-desmethylate, and N,O-didesmethylate were 18.2ââ?¬â??564,\n11.8ââ?¬â??137, 4.9ââ?¬â??250, and 6.1ââ?¬â??147 ng/mL in cancer patients, and 32.8ââ?¬â??670, 7.0ââ?¬â??84.8, 5.1ââ?¬â??317, and 6.7ââ?¬â??85.2 ng/mL,\nrespectively, in non-cancer patients.\nConclusions: The present method with acceptable analytical performance can be helpful for evaluating the\npharmacokinetics of oral tramadol, including the determination of its desmethylates, for patients with cancer pain or noncancer\npain in clinical settings....
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