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Faculty of Pharmacy

 

Recent Submissions

  • Laakso, Johanna (2022)
    The operation of community pharmacies has developed extensively over the past decades, with special emphasis on medication counselling services. In addition to dispensing, pharmacies can offer various kinds of clinical pharmacy services, such as medication reviews, automated dose dispensing and other services to support rational use of medicines. All this activity requires patient information, which is currently available in pharmacies only from prescriptions, reimbursement information, and by asking the customer. Because of this, a need to increase the availability of patient information in pharmacies has come up. The aim of this study was to determine what kind of patient information should be available in community pharmacies for 1) the statutory dispensing of medicines, the medication counselling and treatment monitoring, and 2) other services related to promotion of health and well-being and prevention of diseases. Furthermore, the study investigated experts' experiences of the sufficiency of patient information in pharmacies, as well as in what form and from what period the information should be available in pharmacies. The study was conducted as a 3-round Delphi study with an expert panel consisting of 20 pharmacists specialized in clinical pharmacy. Consensus was formed with the help of a preliminary patient information list which had been compiled based on the literature and the expertise of the research group (a total of 39 patient data items). The limit of the experts' consensus was set to ≥80%. The Delphi-rounds were conducted as electronic surveys during the spring and summer of 2022. The responses were analysed using quantitative and qualitative methods. Most of the expert panellists (n=20) perceived that the patient information available in community pharmacies was insufficient. This study reached a strong consensus that pharmacies should have quite a large set of patient information available both for dispensing medicines and medication counselling, and for providing services supporting rational use of medicines. Of the patient data items, nine reached the consensus line concerning dispensing of medicines and 31 measures concerning other services. From both points of view, information about the client's diagnoses, blood pressure, and the GFR value indicating kidney function were rated as the most important to be available in community pharmacies. However, the panellists also reported challenges to overcome in the access and utilization of the patient information, for example, related to current legislation, resources, and competences of pharmacists. These aspects should be considered in the development of community pharmacy practice and electronic patient information (e.g., Kanta services).
  • Niemissalo, Sanna (2022)
    The aim of this master’s thesis was to investigate whether drug-induced inhibition of cytochrome P450 enzymes (CYP), especially time-dependent inhibition (TDI), could be the reason for bioaccumulation of the pharmaceuticals present in the aquatic environment in fish and whether the in vitro method could identify pharmaceuticals causing an environmental risk, which should primarily be investigated more closely. The half-maximal inhibitory concentrations (IC50) of seven antimicrobial drugs detected in the environment (erythromycin, clarithromycin, ketoconazole, clotrimazole, miconazole, ciprofloxacin, and sulfamethoxazole) and three known human time-dependent inhibitors (furafylline, diltiazem and verapamil) chosen for the validation of the method, were determined by EROD (7-ethoxy-resorufin-O-deethylase) and BFCOD (7-benzyloxy-4-trifluoromethyl-coumarin-O-debenzyloxylase) activities. The IC50 shift method and commercially available rainbow trout (Oncorhynchus mykiss) liver microsomes were used in determinations. The known human time-dependent inhibitors chosen for the validation of the method, furafylline (EROD) and diltiazem (BFCOD) proved to be possible time-dependent inhibitors also in rainbow trout in vitro, but this was not observed for verapamil (BFCOD). All antimicrobial drugs, except ciprofloxacin, inhibited more selectively BFCOD-reaction, as in human. In the case of sulfamethoxazole, inhibition was not observed at the concentrations used (0–500 µmol/L). Both enzyme activities (EROD and BFCOD) were inhibited in rainbow trout by ketoconazole, clotrimazole and miconazole. Among antimicrobial drugs acting as time-dependent inhibitors in human, erythromycin inhibited BFCOD activity in a time-dependent manner also in rainbow trout, but this was not observed for clarithromycin. Strongest inhibitors for CYP enzymes of rainbow trout in vitro were ketoconazole (EROD, IC50=4,19 µM and BFCOD, IC50=2,31 µM) and clotrimazole (EROD, IC50=33,78 µM and BFCOD, IC50=1,55 µM). The IC50 values of diltiazem, erythromycin, clarithromycin, ciprofloxacin, and verapamil were of the same order of magnitude as in human. The IC50 values of furafylline, ketoconazole, clotrimazole and miconazole were several times higher in rainbow trout than in human. Based on the results of this study, the IC50-shift method is also valid for fish, but there are differences in the inhibition potencies between human and fish, and the inhibition potency of human CYP enzymes cannot therefore directly predict enzyme inhibition of fish or the mechanism of inhibition. The In vitro measured IC50 values of rainbow trout were several orders of magnitude higher than the average concentrations of the pharmaceutical residues measured in the environment. Exposure to pharmaceutical mixtures is long-term, so interactions and bioaccumulation may still be possible due to inhibition of CYP enzymes. Developing a valid in vitro method for environmental risk assessment would be important, as animal experiments are ethically challenging.
  • Kulmala, Veera (2022)
    Parkinson’s disease (PD) is a progressive neurodegenerative disorder with the neuropathological hallmark of intraneuronal inclusions called Lewy bodies (LB). Accumulation of α-synuclein (α-syn) and cellular components into LBs coincides with degeneration of dopaminergic neurons in the midbrain, substantia nigra. Degeneration of dopaminergic neurons eventually leads to motor dysfunctions. Currently, the treatments for PD are symptomatic. For this reason, new disease-modifying treatments are needed to slow down or prevent the disease progression. Neurotrophic factors (NTFs) have been an interest of research for a couple of decades because of their neuroprotective properties. The main aim of this study was to investigate if brain-derived neurotrophic factor (BDNF) reduces pre-formed fibril (PFF) induced aggregation of α-syn in dopaminergic neurons. PFF-model was used to mimic the accumulation of LBs in neurons, as PFFs induce aggregation of endogenous α-syn in neurons. Additionally, the dose dependence of BDNF was tested. The secondary objective was to investigate the interaction of tropomyosin receptor kinase B (TrkB) signaling pathway and α-syn aggregation using TrkB agonists and antagonists. The cultured dopaminergic neurons isolated from the midbrain of mouse embryos were treated with PFFs on the day in vitro (DIV) 8. BDNF or control treatments were added either 1 hour after the PFF-treatment or on DIV 12. Neurons were fixed on DIV 15 and fluorescent immunohistochemistry was performed. After the detection of fluorescence with automated, high-content imaging, image analysis was done for quantifying dopaminergic neurons, and dopaminergic neurons positive for LB-like aggregates by using unbiased image analysis CellProfilerTM software. Both BDNF and positive control glial cell line-derived neurotrophic factor (GDNF) significantly reduced LB-like aggregates in dopaminergic neurons at both timepoints. GDNF was more effective at both timepoints than BDNF. Both tested doses of BDNF lowered the number of LB-like aggregates, but a more robust effect was seen with the higher dose. The highest tested dose for the TrkB agonists was toxic to the cultured dopaminergic neurons, whereas the lower doses did not affect either the survival or the number of LB-like aggregates. BDNF promoted the survival of the dopaminergic neurons despite the survival-reducing adverse effect of TrkB antagonist K252a. This study provided new information on the effects of exogenously added BDNF on PFF-model with primary neuronal culture. Research on the underlying mechanisms of α-syn aggregation and the protective effects of NTFs can forward the development of new therapies against PD.
  • Micklin, Maria (2022)
    Indomethacin is in a BCS-classification class two drug, meaning it has poor solubility but good permeability. Because of this solubility is a limiting factor for it reaching bloodcirculation. Amorphous form has better solubility than crystalline form. Most common problems with amorphous form are poor stability and process technical problems. In this study Indomethacin was combined with two different kind of polymers that were prepared by hot-melt extrusion. By hot-melt extrusion we can get more stable product than pure amorphous drug. These polymers were polyvinylpyrrolidone (PVPK179 and polyvinylpyrrolidonevinylacetate (PVPVA). They were prepared with Indomethacin 1:1 mass ratio. The aim was to study these extrudates and their stability, cumulative release and especially permeability. By using differential scanning calorimetry, X-ray diffraction and polarized light microscopy it was possible to analyze whether the drug was amorphous or crystalline. In the study it was found that by using hot-melt extrusion it was possible to make amorphous combinations of Indomethacin and polymers. Their permeability was between crystalline and amorphous form. PVPK17-Indomethacin combination had better permeability than PVPVA-Indomethacin combination. On the other hand PVPVA-Indomethacin had better cumulative release than PVPK17-Indomethacin combination
  • Miinalainen, Annika (2022)
    OATP2B1 is a transmembrane transport protein expressed widely in the human body and transports both endogenous compounds and several drugs from outside the cell into the cytoplasm. The abundant expression of OATP2B1 in pharmacokinetically important tissues such as in the intestine, liver, and kidney suggests an important role in the drug absorption and elimination process, although research data on the clinical significance of OATP2B1 is still limited. Several drugs inhibit the function of OATP2B1, creating a risk for drug-drug interactions. OATP inhibition by some inhibitors is time-dependent, which may lead to more potent in vivo effects than expected. In this study, the time dependence of OATP2B1 inhibition by five different drugs was evaluated using OATP2B1-overexpressing HEK293 cells. IC50 values of inhibitors for OATP2B1-mediated uptake of DBF and E1S were determined with and without preincubation for 20 minutes. In addition, the in vivo interaction potential of the inhibitors in the intestine, liver, and other tissues was evaluated by utilizing the FDA and EMA guidelines. All five drugs showed effective and concentration-dependent OATP2B1 inhibition with IC50 values of 0.12– 8.82 µM. Furthermore, the inhibition of OATP2B1-mediated DBF uptake by ticagrelor and atorvastatin was time-dependent, while the effect of pre-incubation remains below the limit for the other inhibitors. The inhibitory effect of ticagrelor continued even after the inhibitor was removed from the inhibition buffer. All five inhibitors showed the potential to cause in vivo OATP2B1 inhibition in the intestine, which could result in decreased absorption of the co-administered substrate drug. About erlotinib, the risk of interaction also appeared in the liver, which could reduce the transfer of the substrate drug to the liver and thus lower its elimination rate. In this study, pre-incubation did not affect the in vivo interaction potential of the inhibitor drugs. The results indicate that drug-induced inhibition of OATP2B1 may be time-dependent and therefore can lead to interactions at lower concentrations than expected. For this reason, evaluating the time dependence would be appropriate when assessing transport protein-mediated interaction risk. The results of this study can be utilized in designing clinical interaction studies and in understanding the results.