A rapid and sensitive LC-MS/MS method for quantifying oxycodone, noroxycodone, oxymorphone and noroxymorphone in human plasma to support pharmacokinetic drug interaction studies of oxycodone.

A sensitive and reliable LC-MS/MS method was developed and validated for the quantification of oxycodone and metabolites in human plasma. The method has a runtime of 6 min and a sensitivity of 0.1 µg/L for all analytes. Sample preparation consisted of protein precipitation. Separation was performed on a Kinetix biphenyl column (2.1 × 100 mm, 1.7 µm), using ammonium formate 5 mm in 0.1% aqueous formic acid and methanol LC-MS grade 100% in gradient elution at a flow rate of 0.4 ml/min. Detection was performed in multiple reaction monitoring mode using positive electrospray ionization. The method was linear over the calibration range of 0.1-25.0 µg/L for oxycodone, noroxycodone and noroxymorphone and 0.1-5.0 µg/L for oxymorphone. The method demonstrated good performance in terms of intra- and interday accuracy (86.5-110.3%) and precision (CV 1.7-9.3%). The criteria for the matrix effect were met (CV < 15%) except for noroxymorphone, for which an additional method was applied to compensate for the matrix effect. Whole blood samples were stable for 4 h at room temperature. Plasma samples were stable for 24 h at room temperature and 3 months at -20°C. Furthermore, the method was successfully applied in a pharmacokinetic drug interaction study of oxycodone and enzalutamide in patients with prostate cancer.

Lean Body Mass and Total Body Weight Versus Body Surface Area as a Determinant of Docetaxel Pharmacokinetics and Toxicity.

AIM: This study examined whether anthropometric and body composition parameters such as body surface area (BSA), lean body mass (LBM), and total body weight (TBW) are correlated with docetaxel clearance and exposure by analyzing area under the curve. In addition, LBM, TBW, and a fixed dose were compared with BSA as dosing parameters for dose individualization of docetaxel. METHODS: Thirty-six patients receiving docetaxel chemotherapy for breast or metastatic castration-resistant prostate carcinoma were included. Before treatment, LBM was measured using a dual-energy X-ray absorptiometry scanner. Blood samples were collected up to 180 minutes after dosing to analyze docetaxel concentrations and determine individual pharmacokinetic parameters. RESULTS: No significant correlations were found between docetaxel clearance and the anthropometric and body composition variables (BSA, LBM, and TBW). The area under the curve was significantly but poorly correlated with BSA [r = 0.452 ( P = 0.016)] and TBW [r = 0.476 ( P = 0.011)]. The mean absolute percentage error and mean error of simulated dosing based on LBM and fixed dosing were not significantly different from those of BSA. For TBW, only mean absolute percentage error was significantly higher compared with dosing based on BSA (24.1 versus 17.1, P = 0.001). CONCLUSIONS: There was no clinically relevant correlation between docetaxel pharmacokinetics and the anthropometric and body composition variables BSA, LBM, and TBW. Therefore, dose individualization of docetaxel based on LBM, TBW, or fixed dosing cannot be recommended over BSA-based dosing.

[Suicide attempts with castor beans and jequirity beans]. / Tentamen suicidii met wonderbonen en paternosterbonen.

BACKGROUND: Intoxications by beans can have serious consequences. We describe 2 auto-intoxications using castor beans and jequirity beans with the toxins ricin and abrin, respectively. Both toxins have similar mechanisms of action. When taken orally, a toxic mucositis develops causing dehydration, gastrointestinal blood loss and multi-organ failure. Knowledge about pathophysiology is important for risk assessment and treatment. CASE DESCRIPTION: Patient A presented 27 hours after ingestion of the castor beans with frequent vomiting and watery diarrhea. Patient B presented 45 minutes after ingestion of jequirity beans without physical complaints. Gastric lavage and bowel lavage was started. The clinical course in both patients was mild. The severity of toxicity depends on how much the beans have been chewed and the amount of ricin/abrin per bean. CONCLUSION: Intoxications with ricin or abrin can be potentially serious. There is no antidote. Treatment consists of anti-absorptive measures and best supportive care.

Binding interactions with sevelamer and polystyrene sulfonate in vitro.

This study explored the binding of 28 drugs, which were selected based on frequency of concomitant use and chemical properties, to sevelamer and polystyrene sulfonate in vitro. The relative binding was determined by dissolving the investigated drugs alone (=control), together with 800 mg of sevelamer and 15 g of polystyrene sulfonate at different pH levels (1.5, 5.5, and 7.4), respectively. After incubation at 37℃ and shaking for 60 min, the solutions were diluted and centrifuged, and the drug concentrations were quantified with validated analytical assays. The binding assays were performed in threefold. The mean relative binding (MRB) at each pH level was calculated, with a MRB >20% for at least one pH level to be considered as relevant binding. Fourteen and 23 potentially new binding interactions were identified with sevelamer and polystyrene sulfonate, respectively. These potentially new binding interactions have to be studied in vivo to assess their clinical relevance.

Prevalence and follow-up of potentially inappropriate medication and potentially omitted medication in older patients with cancer - The PIM POM study.

OBJECTIVES: To determine the prevalence of Potentially Inappropriate Medication (PIMs) and Potentially Omitted Medication (POMs) in older patients with cancer. MATERIALS AND METHODS: In this prospective observational study (hospital) pharmacists conducted comprehensive medication reviews in older patients with cancer (aged ≥65 years) receiving parenteral chemotherapy and/or immunotherapy at the Deventer Hospital. PIMs and POMs were identified using the Screening Tool of Older Persons' potentially inappropriate Prescriptions (STOPP), the Screening Tool to Alert doctors to the Right Treatment (START), and pharmacists' expert opinion. Recommendations regarding PIMs and POMs were communicated to the patient's oncologist/haematologist and follow-up was measured. Associations between covariates and the prevalence of PIMs and POMs were statistically analysed. RESULTS: For the 150 patients included, 180 PIMs and 86 POMs were identified with a prevalence of 78%. Using pharmacists' expert opinion in addition to only STOPP/START criteria contributed to 49% of the PIMs and 23% of the POMs. A follow-up action was required in 73% of the 266 PIMs and POMs. Number of medicines and Charlson Comorbidity Index score were both associated with having at least one PIM and/or POM (p = .031 and p = .016, respectively). CONCLUSION: The prevalence of PIMs and POMs and subsequent follow-up in older patients with cancer is high. A pharmacist-led comprehensive medication review is a good instrument to identify these PIMs and POMs and to optimize patients' treatment. A complete approach, including pharmacists' expert opinion, is recommended to identify all PIMs and POMs in clinical practice.

Extracorporeal treatment of metforminassociated lactic acidosis in clinical practice: a retrospective cohort study.

PURPOSE: To assess whether extracorporeal treatment (ECTR) improves outcome of patients with metformin-associated lactic acidosis (MALA) and to evaluate the clinical applicability of the Extracorporeal Treatments in Poisoning Workgroup (EXTRIP) criteria for starting ECTR in metformin poisoning. METHODS: Patients with metformin serum concentrations above 2 mg/l who were admitted in the Deventer Teaching Hospital between January 2000 and July 2019 and complied with the definition of MALA (pH < 7.35 and lactate concentration > 5 mmol/l) were included. Mortality and clinical parameters of patients treated with ECTR or not were compared. In addition, treatment of MALA in clinical practice was verified against the criteria of EXTRIP. RESULTS: Forty-two patients were included. Lactate (13.8 versus 10.5 mmol/l, p = 0.01), creatinine (575 versus 254 umol/l, p < 0.01)), metformin (29.4 versus 8.6 mg/l, p < 0.01) concentrations, and vasopressor requirement (72% versus 23%, p < 0.01) were significantly higher in the ECTR-group. Blood pH (7.05 versus 7.19, p = 0.03) and bicarbonate (6 versus 11 mmol/l, p < 0.01) were significantly lower. Mortality, length of hospital stay, and mechanical ventilation requirement were not statistically different. In 83% of patients, treatment of MALA was in accordance with the EXTRIP criteria. CONCLUSIONS: Although there was no statistical benefit in mortality shown from ECTR, ECTR might be lifesaving in MALA, considering the ECTR-group was significantly sicker than the non-ECTR-group. The majority of patients were treated in line with the EXTRIP criteria. Severity of lactic acidosis and renal impairment were the main indications for initiating ECTR.

Pharmacist-led medication reviews in pre-dialysis and dialysis patients.

BACKGROUND: Pre-dialysis and dialysis patients are at risk for drug related problems (DRPs) due to a high incidence of comorbidities. Pharmacist-led medication reviews might reduce the number of DRPs. OBJECTIVES: The aim of this study was to evaluate pharmacist-led medication reviews in pre-dialysis and dialysis patients by determining the number and type of DRPs, nephrologist acceptance of pharmacist interventions and time investment. METHODS: From September 2017 until December 2018, pharmacist-led medication reviews were performed on pre-dialysis and dialysis patients. DRPs (medication discrepancies, prescribing issues related to drug and dose selection, drug use problems) were identified using the pharmacists' expert opinion and the STOPP/START criteria. Number and type of accepted pharmacist interventions, sustainability of interventions after at least 1 month and time investment were determined. Practical barriers in the process were appraised. RESULTS: One-hundred twenty five patients were reviewed: 37 pre-dialysis and 88 dialysis patients. In 100 (80%) patients 277 medication discrepancies were identified of which 224 (81%) were accepted by the nephrologist. Pharmacists suggested 422 interventions concerning drug or dose selection for 115 patients; 106 interventions were accepted by the nephrologist, which resulted in 60 patients having medication changed. Ninety percent of those changes remained implemented on follow-up after at least 1 month. In 46 (37%) patients, the clinical pharmacist detected DRPs concerning the drug use process and performed patient counseling. The average time investment was 85 min per patient for the clinical pharmacist and 15 min for the nephrologist. Besides time investment, unclear responsibility for medication management due to multiple prescribers was an important barrier in the process and the main reason for nephrologists to reject pharmacist interventions. CONCLUSION: Pharmacist-led medication reviews in pre-dialysis and dialysis patients led to medication changes in half of the patients. However, efficiency should be improved before adopting pharmacist-led medication reviews into clinical practice.

[Strychnine poisoning: uncommon, but does still happen]. / Strychnine-intoxicatie: zeldzaam maar niet verdwenen.

BACKGROUND: Acute strychnine poisoning is an uncommon form of intoxication, characterized by severe tonic clonic seizures and tetanus-like contractions while the patient is fully conscious. It can result in respiratory failure, leading to death. CASE DESCRIPTION: A 47-year-old man was admitted to the casualty department 2 hours after self-poisoning with strychnine. The clinical picture consisted of persistent seizures, which were treated with midazolam and propofol. The patient went into respiratory failure and asystole, so intubation and cardiac massage were initiated. Other complications were severe metabolic acidosis, hyperthermia and rhabdomyolysis with renal failure. The treatment consisted of cooling, hyperhydration and intravenous administration of sodium bicarbonate. He was discharged to a mental care institution with no persistent symptoms 11 days later. CONCLUSION: Early aggressive treatment of a strychnine intoxication can be life-saving. Knowledge of the clinical picture and the right treatment is important. Treatment is primarily focussed on stopping the convulsions and securing the airway.

[No quetiapine for sleeping disorders]. / Geen quetiapine bij slaapstoornissen.

The prescribing of low doses of quetiapine for the treatment of sleeping disorders appears to be widespread. Recently, in a systematic literature review on low-dose quetiapine use for the treatment of sleeping disorders, it was concluded that evidence for its efficacy is currently lacking. Furthermore, quetiapine is probably associated with potentially severe adverse effects, also at low doses. In conclusion, sufficient scientific evidence that justifies the current practice of off-label prescribing of low-dose quetiapine for the treatment of sleeping disorders is insufficient; further research into its efficacy and safety is needed.

Analysis of medication information exchange at discharge from a Dutch hospital.

BACKGROUND: At hospitalisation and discharge the risk of errors in medication information transfer is high. OBJECTIVE: To study the routes by which medication information is transferred during discharge from Deventer Hospital, and to improve medication information transfer. SETTING: Eight hospital wards of the Deventer Hospital. METHOD: From December 6 to 17th 2010, the following data was recorded across eight hospital wards: the identification number of discharged patients, the date of discharge and the route by which medication information was transferred. The possible route categories recorded were the Pharmacy Service Point, the hospital's public pharmacy, and "other" routes (which had to be specified). Validation of the data was performed by cross-checking the information collected by the hospital's Admission Office, the Pharmacy Service Point and the hospital's public pharmacy, in addition to electronic patient files, interviews with ward staff and, where necessary, interviews with the concerned patients. Main outcome measure Route of medication information transfer at discharge in all discharged patients. RESULTS: A total of 629 patients were included in the study. The routes of transfer were: Pharmacy Service Point 281 patients (44 %), the hospital's public pharmacy 54 patients (9 %), and other routes 44 patients (7 %). Other routes were most recorded at the children's ward, the short stay and cardiology ward. In 250 patients (40 %), there was no transfer of information by the Pharmacy Service Point because they were registered as using no medication or as experiencing no medication changes during hospitalisation. CONCLUSION: Medication information was transferred for 53 % of the discharged patients, which is close to the maximum achievable result. Further improvement of medication transfer in Deventer Hospital can be made by adjusting the current procedure and by educating the ward staff about the importance and the clinical practice of this procedure.