Het Nederlands Platform voor Farmaceutisch Onderzoek (NPFO) presenteert onderzoek in de farmaceutische wetenschappen. De nadruk ligt op klinische toepassing zoals medicatieveiligheid, patiëntenzorg, formulering, analyse, farmacologie en casuïstiek.
The effect of a customized medication verification tool on the amount of unintended clinically relevant medication discrepancies at hospital admission of psychiatric patients
BACKGROUND
Unintended medication discrepancies (UMDs) at admission is common in hospitalized patients. Studies have shown that medication verification at admission resulted in fewer UMDs. Medication reconciliation studies in psychiatric patients are scarce. At the time of this study, medication verification in the medical psychiatric unit (MPU) of the Elisabeth-Tweesteden Hospital was done by the attending physician. After evaluating this process a customized verification tool was developed.
OBJECTIVE
The effect of using a customized medication verification tool by a pharmacy technician on the prevention of clinically relevant UMDs in psychiatric patients admitted to the MPU of the Elisabeth-Tweesteden Hospital.
DESIGN
A randomized prospective intervention study.
METHODS
Patients admitted to the MPU – who met the inclusion criteria – were randomized in group A, B or C. In group A medication was verified by the attending physician. In group B and C medication was verified by a pharmacy technician using a standardized or customized verification tool, respectively. UMDs were assessed within 24 hours of admission. A panel determined clinical relevancy of the UMDs using the National Coordinating Council for Medication Error Reporting and Prevention (NCCMERP) index. Categories E till I were considered clinically relevant.
RESULTS
The interim analysis showed 33 UMDs in group A (n = 31), 59 in group B (n = 44), and 88 in group C (n = 42). The amount of clinically relevant UMDs per patient in group A, B, and C was 0.32, 0.27, and 0.57, respectively. The majority of the UMDs were omissions and included mostly non-psychiatric medication.
CONCLUSION
The interim analysis shows relatively more clinically relevant UMDs per patient when medication was verified by a pharmacy technician using a customized verification tool. It is possible that medication verification with a customized verification tool by a pharmacy technician results in the prevention of clinically relevant unintended medication discrepancies.
Variability in pharmacokinetics of intravenous paracetamol in healthy older people
BACKGROUND and OBJECTIVE
Paracetamol is the most used analgesic in older people. The physiological changes occurring with ageing influence the pharmacokinetics of paracetamol and its variability. A population pharmacokinetic analysis to describe the pharmacokinetics of intravenous paracetamol in fit older people was performed. Thereafter, simulations were conducted to illustrate target attainment and variability of paracetamol exposure following current dosing regimens (1000 mg q6h, q8h) using steady-state concentration (Css-mean) of 10 mg/L as target for effective analgesia.
DESIGN and METHODS
A population pharmacokinetic-analysis, using NONMEM 7.2, was performed based on 601 concentrations of paracetamol from 30 fit older people (median age = 77.3 years [61.8- 88.5], body weight = 79 kg [60-107]). All had received an intravenous paracetamol dose of 1000 mg – over 15 min – after elective knee surgery.
RESULTS
A two-compartment pharmacokinetic-model best described the data. Volume of distribution of paracetamol increased exponentially with body weight. Clearance was not influenced by any covariate. Simulations of the standardized dosing regimens resulted in a Css-mean of 9.2 mg/L (q6h) and 7.2 mg/L (q8h). Variability in paracetamol pharmacokinetics resulted in a Css-mean above 5.4 (q6h) and 4.1 mg/L (q8h) in 90%, and above 15.5 (q6h) and 11.7 mg/L (q8h) in 10% of the population.
CONCLUSION
The target concentration was achieved in the average patient with 1000 mg q6h, while q8h resulted in underdosing for the majority of the population. Due to large unexplained inter-individual variability in paracetamol pharmacokinetics a relevant proportion of the fit older people remained either under- or overexposed.
Association of single-nucleotide polymorphisms in UGT1, NR1I2, ABCC2, ABCC5 and ABCG1 with irinotecan-induced toxicity in colorectal cancer
BACKGROUND
Irinotecan is used in the palliative treatment of metastatic colorectal cancer. Its metabolism is complex with many different transporters and enzymes involved. For UGT1A1*28 (rs8175347), an association with irinotecan-induced toxicity has been established. Recent studies suggested that other single-nucleotide polymorphisms (SNPs) within genes encoding irinotecan-related enzymes and transporters can lead to reduced or increased irinotecan-induced toxicity, mainly diarrhoea and neutropenia.
OBJECTIVE
In this study we aim to replicate associations between SNPs related to UGT1 rs11563250; NR1I2 rs10934498, rs2472677, rs3814055 and rs1523127; ABCC5 rs10937158, rs3749438, rs562 and rs2292997; ABCG1 rs225440 and ABCC2 rs717620 and grade 3 to 4 diarrhoea and febrile neutropenia in a population of 221 mCRC patients treated with irinotecan. The well-known UGT1A1*28 variant is also evaluated.
DESIGN
Retrospective clinical association study.
METHODS
DNA samples used for this study were obtained from patients participating in the CAIRO study (NCT00312000). The DNA samples were genotyped for twelve SNPs, selected on the basis of the results of previously published studies. For the main analysis, associations between SNPs and toxicity data were tested with logistic regression.
RESULTS
ABCC2 rs717620T is significantly associated with grade > 3 febrile neutropenia (OR = 2.72; P = 0.025). UGT1A1*28 shows significant associations with an increased risk on grade 3 to 4 diarrhoea (OR = 1.76, P = 0.035) and grade 3 to 4 febrile neutropenia (OR = 3; P = 0.01).
CONCLUSION
The outcomes of previous studies could not be replicated, except for UGT1A1*28. Moreover, we found an association with the opposite direction of effect between ABCC2 rs717620T and severe neutropenia. Based on the outcomes of this study genotyping for the tested variants – with exception of UGT1A1*28 – cannot be recommended.
Therapeutic use of low molecular weight heparins in obese patients: dosing based on body weight without cut-off limit
BACKGROUND
The correct dose of therapeutic low molecular weight heparins (LMWHs) in patients with a body mass index ≥ 30 kg/m2 is uncertain. Literature and guidelines are not clear and consistent about the correct dose.
DESIGN and METHODS
In this review, an overview of the literature on therapeutic use of LMWHs in this population is provided. Sixteen pharmacokinetic and pharmacodynamic or clinical studies were included.
RESULTS
Based on these results, obese patients should receive therapeutic doses of LMWHs, based on their total body weight without a dose cap as recommended in the Summary of Product Characteristics. In patients with morbid obesity, anti-Xa level monitoring and subsequently an adjusted dosage on the base of supratherapeutic anti-Xa levels is recommended.