Exploration of the regional effects of colchicine in the LoDoCo2 trial.

Background: The Low Dose Colchicine 2 (LoDoCo2) trial randomized 5,522 patients with chronic coronary disease to colchicine 0.5mg daily or placebo in a 1:1 ratio and demonstrated the cardiovascular benefits of colchicine. In the trial, which was conducted in Australia and The Netherlands, a prespecified subgroup analysis suggested a difference in magnitude of treatment effect of colchicine by region (Australia: HR 0.

Validation of Population Pharmacokinetic Models for Clozapine Dosage Prediction.

Background: Clozapine is unique in its capacity to ameliorate severe schizophrenia but at high risk of toxicity. A relationship between blood concentration and clinical response and evidence for concentration-response relationships to some adverse effects justify therapeutic drug monitoring of clozapine. However, the relationship between drug dose and blood concentration is quite variable.

Evaluating the Efficacy, Toxicity and Pharmacokinetic Profile of Oral Busulfan in Allogeneic Stem Cell Transplant Patients.

Background: Oral busulfan and intravenous cyclophosphamide (Bu/Cy) are common myeloablative preparations used in allogeneic hematopoietic stem cell transplantation (HSCT). Herein, we investigated the safety of (Bu/Cy) administration during HSCT.

Methods: Patients administered Bu/Cy for allogeneic HSCT at Royal Perth Hospital and Fiona Stanley Hospital between 2007 and 2017 were reviewed for inclusion in the study.

Two-Photon Polymerization: Fundamentals, Materials, and Chemical Modification Strategies.

Two-photon polymerization (TPP) has become a premier state-of-the-art method for microscale fabrication of bespoke polymeric devices and surfaces. With applications ranging from the production of optical, drug delivery, tissue engineering, and microfluidic devices, TPP has grown immensely in the past two decades. Significantly, the field has expanded from standard acrylate- and epoxy-based photoresists to custom formulated monomers designed to change the hydrophilicity, surface chemistry, mechanical properties, and more of the resulting structures.

Hematocrit Correction of Whole Blood Phosphatidylethanol Concentrations to Estimate Erythrocyte PEth Concentrations: Sensitivity, Specificity and Influence on Test Utility.

Phosphatidylethanol (PEth) forms in erythrocyte membranes after alcohol consumption, offering a persisting biomarker, that is measurable in whole blood, washed erythrocytes and dried blood spots. For a predominantly erythrocyte-restricted analyte, erythrocyte concentrations seem to have most validity in patients who are anemic through alcoholism or other pathologies, despite preparation increasing assay complexity. Differences in specimen preparation alter PEth concentrations for the same patient, meaning that criteria for interpreting PEth results should relate to specimen type, presenting a barrier to achieving harmonization.

Validation of a liquid chromatography tandem mass spectrometry (LC-MS/MS) method for erythrocyte phosphatidylethanol revealing critical considerations for its use as a clinical biomarker.

Erythrocyte membrane-incorporated phosphatidylethanol (PEth) forms only in the presence of ethanol and, once formed, provides a persisting marker for historical alcohol consumption. Relationships between PEth concentration, extent of consumption and time from consumption are under investigation. Threshold values of PEth have been proposed as indicators for any, or for harmful alcohol consumption.

A rapid, LC-MS/MS assay for quantification of piperacillin and tazobactam in human plasma and pleural fluid; application to a clinical pharmacokinetic study.

Piperacillin, in combination with tazobactam is a common first-line antibiotic used for the treatment of pleural infection, however its pleural pharmacokinetics and penetration has not previously been reported. The objective of this work was to develop and validate a rapid and sensitive liquid chromatography with tandem mass spectrometry (LC-MS/MS) assay for quantification of piperacillin (PIP) and tazobactam (TAZ). PIP and TAZ were extracted from both human plasma and pleural fluid samples by protein precipitation in methanol containing the internal standards (IS) piperacillin-d (PIP-d) and sulbactam (SUL).

Development of a population pharmacokinetic model for parecoxib and its active metabolite valdecoxib after parenteral parecoxib administration in children.

Background: Parecoxib is a cyclooxygenase-2 selective inhibitor used in management of postoperative pain in adults. This study aimed to provide pediatric pharmacokinetic information for parecoxib and its active metabolite valdecoxib.

Methods: Thirty-eight children undergoing surgery received parecoxib (1 mg/kg IV to a maximum of 40 mg) at induction of anesthesia, and plasma samples were collected for drug measurement.

Transfer of parecoxib and its primary active metabolite valdecoxib via transitional breastmilk following intravenous parecoxib use after cesarean delivery: a comparison of naive pooled data analysis and nonlinear mixed-effects modeling.

Background: Multimodal analgesia, including nonopioid analgesics, is usually used for several days after cesarean delivery. Because the breastfed infant receives transitional milk during this same period, it is important to know how much of a maternal analgesic drug is received by the infant. We designed this study to estimate infant exposure to parecoxib and its active metabolite valdecoxib (a cyclooxygenase-2 inhibitor) after a single IV maternal dose of parecoxib after cesarean delivery.

MexTAg mice exposed to asbestos develop cancer that faithfully replicates key features of the pathogenesis of human mesothelioma.

Animal models provide an important tool for investigating the biology of cancer and for testing the efficacy of novel treatments. Here we describe several aspects of the transgenic MexTAg mouse that develops asbestos-induced mesothelioma. Targeted expression of the TAg transgene causes mesothelioma to develop more rapidly after asbestos exposure in wild-type mice with 100% incidence compared to 30% incidence in wild-type mice.

Therapeutic drug monitoring for busulfan in plasma during conditioning chemotherapy for autologous stem cell transplantation in relapsed primary cerebral lymphoma.

Therapeutic drug monitoring for busulfan in plasma during conditioning chemotherapy for autologous stem cell transplantation in relapsed primary cerebral lymphoma has not previously been reported. This case involved a 49-year-old man with relapsed primary cerebral lymphoma who received busulfan (8 mg/kg total dose; 2.67 mg/kg as a 3-hour IV infusion each of days -6 through -4) as part of a multiagent chemotherapy conditioning regimen.

Pharmacokinetic properties of azithromycin in pregnancy.

Azithromycin (AZI) is an azalide antibiotic with antimalarial activity that is considered safe in pregnancy. To assess its pharmacokinetic properties when administered as intermittent preventive treatment in pregnancy (IPTp), two 2-g doses were given 24 h apart to 31 pregnant and 29 age-matched nonpregnant Papua New Guinean women. All subjects also received single-dose sulfadoxine-pyrimethamine (SP) (1,500 mg or 75 mg) or chloroquine (450-mg base daily for 3 days).

Prospective study of 101 patients with suspected drink spiking.

Objective: To evaluate cases of suspected drink spiking presenting to the ED by the prospective collection of standardized relevant historical, clinical and laboratory data.

Methods: A prospective observational study of 101 patients presenting to metropolitan hospital ED with suspected drink spiking within the previous 12 h. Clinical history, including details surrounding the alleged drink spiking incident, and examination.

Evaluation of a deuterium-labeled internal standard for the measurement of sirolimus by high-throughput HPLC electrospray ionization tandem mass spectrometry.

Background: Matrix effects in HPLC-electrospray ionization-tandem mass spectrometry (HPLC-ESI-MS/MS)1 can cause differences in the ionization of an internal standard (IS) compared with the analyte of interest. Unless sample cleanup or chromatographic conditions eliminate or minimize ion suppression or enhancement, variability in interpatient matrices may cause erroneous results. A stable isotope-labeled IS can be used to minimize analytical interpatient variation.