Since clinical pharmacists provide support for pharmacotherapy, pharmacists sometimes encounter unknown side effects and drug interactions. However, by involving pharmacological concepts to establish rules from patients experiencing side effects, adverse effects can be reduced or avoided. In this paper, ways to optimize prescriptions using pharmacokinetic analyses of absorption, distribution, metabolism and excretion in patients who had experienced side effects will be introduced. First, in the absorption phase, the effects of gastrectomy on pharmacokinetic profiles and side effects of oral etoposide were found. Second, in order to prevent diarrhea, which is a major side effect of irinotecan, orally administering Kremezin® to adsorb SN-38, was found effective. In addition, in the distribution phase, the mechanism of interaction between lidocaine and mexiletine during tissue distribution was found. In the metabolism phase, a drug interaction mechanism between theophylline and acyclovir was found. By comparing the ratio between the serum concentration of SN-38G and SN-38, evaluating metabolic capacity rather than UDP-glucuronosyltransferase (UGT) 1A1 polymorphism was found more useful for patients treated with irinotecan. In the excretion phase, a method of drug administration based on creatinine clearance was established, since if treatment with renally excreted medications such as cibenzoline, ribavirin, and vancomycin is performed in accordance with the dosage regimen in the package insert of these drugs, cibenzoline causes hypoglycemia, ribavirin causes anemia, and vancomycin causes renal failure. By clarifying the mechanism of side effects using pharmacokinetics, improving the therapeutic effect by reducing or preventing side effects in the clinical setting is possible.
Conventional dose estimation methods do not consider drug factors and do not allow for various pharmacokinetic factors associated with the growth of children. I have therefore established a new method based on drug elimination processes and physiological and biochemical developmental factors in order to more appropriately estimate pediatric doses (the ePPBD method). Renal excretion or hepatic metabolic clearance was calculated for each age based on physiological and biochemical developmental factors, such as the unbound fraction of the drug in plasma, glomerular filtration rate, tubular secretion, liver volume, and CYP enzyme activity. Then the pediatric dose was estimated by multiplying the adult dose by the pediatric/adult ratio of renal excretion or hepatic metabolic clearance. Accuracy of the ePPBD method was compared with conventional methods, using the population mean clearance and the doses listed in package inserts and text books as the standards to quantitate its validity. In brief, accuracy was evaluated by classifying children into the following age groups: 1) neonates in consideration of the post-conceptional age (PCA), 2) infants up to 2 years old, and 3) children over 2 years old for drugs with renal excretion, or 4) children of all ages for drugs with hepatic metabolism. The accuracy of the ePPBD method was superior to that of conventional methods both for drugs with renal excretion and those with hepatic metabolism, and therefore it should be useful for pediatric patients in whom physiological function changes remarkably as they age.
Recently, use of inhaled corticosteroid anti-asthmatic drugs has been increasing due to the increase of bronchial asthma patients. However, there are some side effects of inhaled corticosteroid, such as hoarseness, which can affect a patient's quality of life (QOL). Therefore, to contribute to the proper and individual use of these anti-asthmatic drugs, we conducted a statistical analysis to determine the cause of hoarseness by collecting information to find a relationship between the rate of patients suffering from hoarseness, their personal backgrounds and each inhaled corticosteroid. In our present study, the rate of hoarseness onset in smokers was 4.15 times higher than that of non-smokers. On the other hand, fluticasone propionate (FP) is the component of inhaled anti-asthmatic drugs, which has the largest average particle size. Rate of hoarseness onset of inhaled FP was higher than any other component of inhaled corticosteroids. However, in inhaled anti-asthmatic drugs having FP as the main corticosteroid component, difference of the onset of hoarseness was observed between five nozzle types of devices. This result suggested that the cause of this difference was derived from the individual shape of the device's nozzle. In this study, it was revealed that the difference in nozzle types of devices and the particle size of drug components affect mainly the occurrence frequency of hoarseness. These results provide helpful information about appropriate use of inhaled anti-asthmatic drugs including effective patient education for self-administration.
Pregabalin, a useful drug for neuropathic pain, has a high incidence of dizziness and somnolence as side effects. In the present study, the incidence of both side effects and the risk factors were retrospectively investigated in hospitalized patients who were administered pregabalin after their admission. In 65 patients (median 68 years old), 34 cancer patients and 18 opioid users were included. Items studied were cancer/non-cancer, opioid user/non-user, fall/nonfall, age, sex, weight, daily dose of opioids, the number of the drugs that may cause dizziness and somnolence, daily dose of pregabalin, and the ratio of creatinine clearance to daily dose of pregabalin. Fourteen (21.5%) and 21 (23.3%) patients developed dizziness and somnolence, respectively, and 4 (6.1%) patients developed fall. In the case of opioid combination, 7 (38.9%) and 10 (55.6%) patients developed dizziness and somnolence, respectively. A logistic-regression analysis showed that opioid use is a significant augmenting risk factor for dizziness (P = 0.026) and somnolence (P = 0.016) of pregabalin. The ratios of daily dose of pregabalin to creatinine clearance did not show any relation to the incidence of dizziness and somnolence; both side effects were observed in some patients whose renal functions were normal. It is suggested that attention is necessary to the incidence of dizziness and somnolence regardless of renal function, and that particular attention is required when opioids, which have similar side effects, are combined with pregabalin.
Gemcitabine therapy has been the standard first-line treatment for patients with unresectable local cancer. However 1-year survival rates of less than 20% have been reported. Therefore, these results are unsatisfactory and also the prognostic factors are still not sufficiently discussed. We retrospectively analyzed the medical records of 88 patients who received gemcitabine mono-therapy for unresectable pancreatic cancer. The patient characteristics and treatment factors that may be associated with the survival as a patient’s prognosis were investigated. The prognostic factors for survival were examined by univariate and multivariate analyses using the log-rank test and Cox proportional hazard analysis, respectively. Multivariate analysis identified gemcitabine total dose (≤ 9075 mg; hazard ratio HR, 3.10; P = 0.001), absence of second-line therapy (HR, 6.30; P < 0.001), stage IV-b (HR, 4.97; P = 0.005), neutrophil counts (> 3979.5 /μL; HR, 3.43; P = 0.003), lymphocyte counts (≤ 1155.5 /μL; HR, 2.94; P = 0.010), and carcinoembryonic antigen (CEA) levels (> 5.95 ng/mL; HR, 2.57; P = 0.034) as prognostic factors. We conducted additional data analysis including treatment regimens, because second-line chemotherapy is one of the prognostic factors. As indicated by the multivariate analysis, S-1 and gemcitabine combination therapy, S-1 and cisplatin combination therapy, and concurrent gemcitabineradiation therapy were not statistically significant when S-1 mono-therapy was the reference arm. In other words, S-1 mono-therapy is equivalent in efficacy when compared to other combination therapy. These prognostic factors could help to select treatment for patients in clinical practice, and these risk-adapted treatment strategies should be further investigated in a prospective study.
This study aimed to develop a questionnaire on pharmacists' responses to pregnant and lactating women, and to investigate changes in pharmacists' awareness regarding such patients after receiving communication skills training (CST). We administered our original questionnaire on the state of explaining to pregnant and lactating patients about taking medication, which involved 2 scales (communication skills and attitude to pregnant and lactating patients), to 112 pharmacists, who attended a seminar in the years 2010-2012 when they trained to become supporters of such patients. As a result of factor analysis, we extracted the following factors: 1) efforts to deliver necessary information, 2) development of a trusting relationship, 3) influence of information and knowledge, 4) respecting privacy, and 5) recognition of treatment. We generally obtained the factor structure that we had expected, which verified the questionnaire's factorial validity. Also, Cronbach's alpha value for each factor was ≥ 0.600, indicating high internal consistency. We also administered the questionnaire to 34 pharmacists who attended the same seminar in the year 2013, in order to investigate changes in their awareness. Their awareness of Factors 2), 4), and 5), which did not change through lectures to promote knowledge, was raised after CST (P < 0.05). Thus it is suggested that this questionnaire could serve as measure of a pharmacist's awareness, and be used for training those pharmacists with insufficient communication skills with pregnant and lactating patients.
Levetiracetam (LEV) is a novel antiepileptic drug that is eliminated primarily through the kidneys, and has little influence on hepatic metabolism such as cytochrome P450 and glucuronidation. These unique characteristics are an advantage of LEV; however, it is only approved for oral administration in Japan. Therefore, we prepared a suppository containing 500 mg of LEV and evaluated serial changes in plasma concentration of LEV after insertion of the suppository. After confirmation of uniformity of our suppositories (499.10 ± 18.71 mg), this agent was administrated to 6 patients with brain tumors, and blood concentration was measured serially: 1, 2, 4, 8 and 12 hours after administration. In comparison with the reported results after oral administration of LEV, the maximum concentration (Cmax) was low, but prolonged time to maximum plasma concentration (Tmax) resulted in a comparable area under the plasma concentration time curve (AUC). These results suggest that the suppository formulations of LEV produced stable and adequate plasma concentration that could provide a different administration route of LEV.
Fifth-grade students in six-year pharmacy schools are required to complete practical training at a pharmacy (11 weeks) and hospital (11 weeks). In our hospital, we developed a training program for pharmacy students on inpatient pharmaceutical care skills. In our inpatient pharmaceutical care program, pharmacy students worked on both internal medicine wards and surgical wards for a total duration of 4 weeks. We adopted the portfolio system on the Web, and pharmacy students submitted case reports to the portfolio system. Furthermore, we added a new practical pathway system to the ward program to construct a high-quality education system. In this study, we examined the educational utility of the practical pathway system in our hospital. The number of case reports submitted by pharmacy students did not alter the introduction of the practical pathway system. However, the rate of learning about drugs significantly increased through the performance of the practical pathway system. It was therefore considered that the practical pathway system is a useful method of providing pharmacy students with inpatient pharmaceutical care skills training to nurture pharmacists.