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1.
Biol Pharm Bull ; 46(10): 1444-1450, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37779046

RESUMO

In Japan, a low-dose transdermal fentanyl (TDF; 0.5 mg) has been approved to address pain in opioid-naïve patients with cancer; however, efficacy and safety data are lacking. To determine the efficacy and safety of TDF, patients with opioid-naïve cancer pain prescribed TDF (0.5 mg/d) and oral oxycodone sustained-release formulation (OXY) 10 mg/d were extracted from electronic medical and nursing records. Overall, 40 and 101 subjects were analyzed in the TDF and OXY groups, respectively. Compared with baseline (median [minimum, maximum]) values, changes in the Numerical Rating Scale (NRS) score on days 1, 3, and 7 post-administration were as follows: TDF (0 [-5, 4]) and OXY (-1.0 [-8, 3]); TDF (-1.5 [-6, 3]) and OXY (-2.0 [-8, 4]); and TDF (-2.0[-6, 3]) and OXY (-3.0[-8, 5]), respectively. No significant difference was observed between the groups on days 1 and 3; however, the change in the NRS on day 7 was significantly higher in the OXY group than that in the TDF group. Regarding adverse events, nausea occurred in 12.5 and 13.9% of patients in the TDF and OXY groups, respectively, while 12.5% of TDF- and 10.9% of OXY-treated patients experienced somnolence, revealing similar occurrence in both groups. However, constipation was more common in the OXY group (TDF: 50.0%, OXY: 71.3%). No serious adverse events (e.g., respiratory depression) were observed in either group. Low-dose TDF (0.5 mg), available only in Japan, showed comparable efficacy and safety to OXY (10 mg/d) and can be a first choice for opioid-naïve patients with cancer pain.


Assuntos
Dor do Câncer , Neoplasias , Humanos , Analgésicos Opioides/efeitos adversos , Fentanila/efeitos adversos , Oxicodona/efeitos adversos , Dor do Câncer/tratamento farmacológico , Analgésicos , Neoplasias/complicações , Neoplasias/tratamento farmacológico , Administração Cutânea
2.
J Pharm Health Care Sci ; 9(1): 7, 2023 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-36803913

RESUMO

BACKGROUND: Cancer-related fatigue (CRF) is one of the most common symptoms in patients with cancer. However, CRF has not been sufficiently evaluated as it involves various factors. In this study, we evaluated fatigue in patients with cancer receiving chemotherapy in an outpatient setting. METHODS: Patients with cancer receiving chemotherapy at the outpatient treatment center of Fukui University Hospital and Saitama Medical University Medical Center Outpatient Chemotherapy Center were included. The survey period was from March 2020 to June 2020. The frequency of occurrence, time, degree, and related factors were examined. All patients were asked to fill out the Edmonton Symptom Assessment System Revised Japanese version (ESAS-r-J) questionnaire, which is a self-administered rating scale, and patients with ESAS-r-J "Tiredness" scores of ≥ 3 were evaluated for factors related to tiredness, such as age, sex, weight, and laboratory parameters. RESULTS: A total of 608 patients were enrolled in this study. Fatigue after chemotherapy occurred in 71.0% of patients. ESAS-r-J "Tiredness" scores of ≥ 3 were observed in 20.4% of patients. The factors related to CRF were low hemoglobin level and high C-reactive protein level. CONCLUSIONS: Twenty percent of patients receiving cancer chemotherapy on an outpatient basis had moderate or severe CRF. Patients with anemia and inflammation are at increased risk of developing fatigue after cancer chemotherapy.

3.
J Pain Palliat Care Pharmacother ; 37(1): 72-77, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36378038

RESUMO

(Case 1) A 45-year-old male was diagnosed with prostate cancer. Treatment was administered using bicalutamide and leuprorelin acetate, while a transdermal fentanyl (TDF) was applied for pain relief. However, TDF continued to peel off owing to excessive sweating, even when reinforced by a protective layer. As such, TDF was discontinued and pain control was initiated using other medicines. Sweating occurred irregularly because of hot flashes, approximately four to five times per day. (Case 2) A 37-year-old male was diagnosed with a malignant thymoma and sacral metastasis. For analgesic control, etodolac tablets, carbamazepine tablets, and TDF were administered. Subsequently, the dose of the TDF was gradually increased, but the analgesic effect was low; thus, fentanyl blood concentration was measured. The measurements showed that even higher TDF doses did not increase fentanyl blood levels. During this period, full body sweating began to occur to a large extent due to unknown causes, and it was thought that the absorption of fentanyl decreased. When using a TDF, it is necessary to monitor patients for any sweating during treatment, while also considering changes in medication in some cases. This should promote the maintenance and improvement of the quality of life of the affected patients.


Assuntos
Fentanila , Neoplasias , Masculino , Humanos , Pessoa de Meia-Idade , Adulto , Analgésicos Opioides , Dor/tratamento farmacológico , Sudorese , Qualidade de Vida , Neoplasias/complicações , Administração Cutânea , Adesivo Transdérmico
4.
J Palliat Med ; 25(4): 686-689, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-34665046

RESUMO

Background: Methadone is frequently used for the management of complex pain at the end of life by palliative care specialists. It is also used in low doses as an add-on therapy to chronic opioid treatment of cancer-related pain, usually with good effect, and without any reported severe adverse effects. However, there are few reports of switching from ketamine to methadone. Case: We report a case of a patient with rectal cancer and intractable pain. Switching from ketamine to methadone to maintain analgesia was successfully carried out without impacting activities of daily living. Established measurement tools, such as numerical rating scale, Douleur Neuropathique, Functional Independence Measure, and Barthel Index, were used. Conclusion: Switching from ketamine to methadone may be beneficial in relieving refractory cancer-related neuropathic pain without decreasing functioning.


Assuntos
Ketamina , Neuralgia , Dor Intratável , Atividades Cotidianas , Analgésicos Opioides , Humanos , Ketamina/uso terapêutico , Metadona , Neuralgia/tratamento farmacológico , Dor Intratável/tratamento farmacológico
5.
J Pain Palliat Care Pharmacother ; 34(4): 203-210, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32870067

RESUMO

Methadone tablets were approved for use in Japan in March 2013. The metabolism of methadone is complex and executed mainly by the cytochromes, CYP3A4 and CYP2B6. The aim of this study was to evaluate the pharmacokinetics of methadone upon oral administration in Japanese patients who experienced cancer-related pain. The concentration of the drug in blood samples was measured in 25 patients undergoing methadone therapy, and the factors leading to variations were investigated. A population pharmacokinetic analysis was evaluated using the Phoenix® NLMETM software. Based on this, the ALBI (albumin-bilirubin) score was identified as a significant factor that could be used to assess variations in the serum concentration of methadone, which was then incorporated into the following final model formula: clearance (L/h) = 5.38 × (ALBI score/-2.139)1.88. The results of these pharmacokinetic parameters suggested that, in clinical use, the dose of methadone should be reduced if liver function declined in patients with cancer-related pain.


Assuntos
Dor do Câncer , Neoplasias , Administração Oral , Dor do Câncer/tratamento farmacológico , Humanos , Japão , Metadona , Neoplasias/complicações
6.
Biol Pharm Bull ; 43(6): 1000-1006, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32475909

RESUMO

In this study, we conducted a pharmacokinetic analysis of tapentadol (TP) in Japanese patients with cancer pain and identified covariates influencing pharmacokinetic parameters. In addition, the analgesic effects and adverse effects of TP were investigated. Data were collected from in-patients with cancer pain who had been administered TP as an extended-release formula. The median (range) estimated clearance (CL/F) and distribution volume (Vd/F) of TP were 86.7 (31.3-213.7) L/h and 1288 (189-6736) L, respectively. There was a strong negative correlation between CL/F and age, Child-Pugh score, and albumin-bilirubin (ALBI) score. The subjects were further divided into two groups according to the factors highly correlated with CL/F. The CL/F of patients in the Child-Pugh B group was 0.46-times that of patients in the Child-Pugh A group. In addition, the CL/F of patients with an ALBI score > -2.40 was 0.56-times that of patients with ALBI scores ≤-2.40, and both differences were statistically significant (p < 0.05). The mean intensity of pain over 24 h was investigated daily from before starting TP for the first 7 d of the treatment. TP reduced pain in six of nine patients; the mean pain visual analogue scale score decreased significantly from 59.2 mm before administration to 42.5 mm at days 5-7. Overall, the Child-Pugh and ALBI scores significantly affected the clearance of TP, which was reduced in patients with impaired liver function. These results suggest that TP is an opioid with a sufficient analgesic effect for cancer patients.


Assuntos
Analgésicos Opioides , Dor do Câncer , Tapentadol , Adulto , Idoso , Idoso de 80 Anos ou mais , Analgésicos Opioides/efeitos adversos , Analgésicos Opioides/sangue , Analgésicos Opioides/farmacocinética , Analgésicos Opioides/uso terapêutico , Dor do Câncer/sangue , Dor do Câncer/tratamento farmacológico , Dor do Câncer/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Tapentadol/efeitos adversos , Tapentadol/sangue , Tapentadol/farmacocinética , Tapentadol/uso terapêutico , Resultado do Tratamento
7.
Artigo em Inglês | MEDLINE | ID: mdl-31308953

RESUMO

BACKGROUND: There is no nationwide data on polypharmacy in palliative care in Japan. In this study, the research committee of the Japanese Society for Pharmaceutical Palliative Care and Sciences conducted an online survey on polypharmacy and inappropriate prescriptions involving its members who worked as hospital pharmacists. METHODS: The online questionnaire included questions about hospital pharmacist interventions for cancer patients who regularly used six or more drugs during a two-month period from October to November 2017. RESULTS: Of 2618 hospital pharmacists, 359 responded (13.7%). With regard to cancer patients receiving opioids, 40.9 and 22.3% of the respondents replied that percentages of patients prescribed six or more regular medications were "40-69%" and "70-99%," respectively. Regarding patients on polypharmacy, 73.0% of the respondents reported a low or moderate rate of inappropriate prescriptions, with responses such as "long-term administration of irresponsible or aimless medications", "adverse drug reactions," and "duplication of the pharmacological effect". Furthermore, 24.2, 46.8, and 23.4% of respondents replied that the rates of drug reduction due to pharmacist recommendations were "0", "1-39%", and "more than 40%," respectively. Pharmacist interventions decreased the use of inappropriate medications, including antiemetics, gastrointestinal medications, and hypnotic sedatives, and reduced or prevented adverse drug reactions such as extrapyramidal symptoms, delirium, and sleepiness. Similar results were obtained for cancer patients who did not use opioids. However, the rates of cancer patients on polypharmacy and with reduction of inappropriate medications by pharmacist interventions were significantly higher in cancer patients receiving opioids. Finally, recommendations of board-certified pharmacists in palliative pharmacy contributed to a decrease in the use of inappropriate medications in cancer patients on polypharmacy (p = 0.06). CONCLUSION: This nationwide survey clarified pharmacist interventions for polypharmacy in palliative care in Japan. Our data showed frequent polypharmacy in cancer patients receiving opioids, and benefits of pharmacist interventions, especially by board-certified pharmacists in palliative pharmacy, for reducing inappropriate medications and improving adverse drug reactions. TRIAL REGISTRATION: The study approval numbers in the institution; 0046. Registered November 6, 2017.

8.
Biol Pharm Bull ; 42(7): 1164-1171, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-30996146

RESUMO

No nationwide study on polypharmacy in palliative care among Japanese community pharmacies has yet been conducted. We conducted an online questionnaire survey for community pharmacist members of The Japanese Society for Pharmaceutical Palliative Care and Sciences regarding their contributions to cancer patients who regularly used six or more drugs, including opioids, in service during the two-month period from October to November 2017. Of 579 community pharmacists, 83 responded to the survey (14.3%). Among them, 47.0 and 27.7% of respondents replied that more than 40% of opioid-using and non-using cancer patients were prescribed six or more regular medications, respectively. The proportion of patients with polypharmacy was marginally higher among opioid-using than non-using patients. Additionally, 31.3 and 22.9% of respondents replied that a low or moderate rate of opioid-using and non-using patients with polypharmacy received inappropriate prescriptions, respectively, including "unnecessary medications," "adverse drug reactions" and "duplication of pharmacological effect." The proportion of patients who received inappropriate prescriptions was significantly higher among opioid-using than non-using patients. Furthermore, 37.3 and 19.3% of respondents replied that pharmacist's recommendations contributed to drug reduction in opioid-using and non-using patients with polypharmacy who received inappropriate prescriptions, respectively. The responders with higher confidence in palliative care showed more success rate for reducing inappropriate medications. Our findings suggest that opioid use can be associated with an increased risk of polypharmacy in cancer patients, and that recommendations by a population of community pharmacists can reduce inappropriate medications and improve adverse drug reactions in both opioid-using and non-using cancer patients with polypharmacy.


Assuntos
Analgésicos Opioides/uso terapêutico , Neoplasias/tratamento farmacológico , Farmacêuticos/estatística & dados numéricos , Polimedicação , Feminino , Humanos , Prescrição Inadequada , Japão , Masculino , Farmácias , Inquéritos e Questionários
9.
Gan To Kagaku Ryoho ; 45(7): 1081-1086, 2018 Jul.
Artigo em Japonês | MEDLINE | ID: mdl-30042277

RESUMO

The objective of our study was to evaluate the efficacy and adverse effects of opioid switching to tapentadol(TP). It was a retrospective survey carried out at the Kitasato University Hospital outpatient clinic between September 2014 and May 2016. We evaluated pain intensity using the visual analogue scale and the occurrence of adverse effects before switching, at the first evaluation after switching, and during the steady state of TP administration. We included 10 patients; of these, 3 patients discontinued TP owing to uncontrolled pain. The conversion ratio of the previously administered opioids to TP was 1.17 at the time of the first evaluation after switching and 1.42 during the steady state. The mean(±SD)pain intensity was 4.2±2.2 before opioid switching and 4.6±2.2 at the time of the first evaluation after switching. The mean(±SD)pain intensity in the 7 patients excluding the 3 patients who discontinued TP was 4.3±2.0 before opioid switching and 2.7±1.9 during the steady state. Somnolence improved in 5 patients and constipation improved in 2 patients when a stable dose was achieved. Opioid switching to TP was appropriately accomplished using the conversion ratio. Furthermore, pain, sleepiness, and constipation improved following successful titration. These data suggest that TP can be useful in the treatment of cancer pain, in addition to the currently used opioid preparations.


Assuntos
Analgésicos Opioides/uso terapêutico , Dor do Câncer/tratamento farmacológico , Fenóis/uso terapêutico , Adulto , Idoso , Analgésicos Opioides/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fenóis/efeitos adversos , Estudos Retrospectivos , Tapentadol
10.
Biol Pharm Bull ; 41(4): 649-651, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29607939

RESUMO

In March 2013, the clinical use of oral methadone tablets was initiated in Japan. There are many factors responsible for the change in blood concentrations of methadone, and its pharmacokinetics is very complex. Therefore, a simple and accurate measurement method for methadone blood concentrations was developed using HPLC/electrochemical detector (ECD). An eluent of 10 mM Na2HPO4/CH3CN/CH3OH (20 : 19 : 3) was used as the mobile phase. The column was used the XTerra® RP18, and the voltage of the ECD was set at 400 to 800 mV. As a result, the calibration curve was linear in the ranges of 10 to 100 ng/mL (y=5012.7x+1041.1, r=0.999). The intra- and inter-day coefficients of variation were <5.2 and <5.8%, respectively. Therefore, this method was considered to be useful for the measurement of methadone blood levels in cancer patients. Also, using this method, blood methadone concentration was measured over time in a patient with cancer-associated pain who was treated with methadone. The estimated clearance (CL/F) and distribution volume (Vd/F) of methadone were 2.84 L/h and 502.8 L, respectively, and took about two weeks to reach steady state.


Assuntos
Analgésicos Opioides/sangue , Metadona/sangue , Idoso de 80 Anos ou mais , Cromatografia Líquida de Alta Pressão , Técnicas Eletroquímicas , Feminino , Humanos
11.
Biol Pharm Bull ; 41(6): 850-857, 2018 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-29526884

RESUMO

Pure oxycodone injection became increasingly necessary after oral oxycodone was launched in Japan in 2003. However, trials clarifying the efficacy and safety of injection are rare. Therefore, a multicenter open study on injection was designed and carried out in 2010, resulting in the launch of injection therapy in 2012. As published domestic case reports on efficacy already show widespread prescription, this study aimed to provide useful information for cancer pain relief in Japan and other countries. Our oxycodone injection study consisted of two trials, one of intravenous (S#9131) and the other of subcutaneous (S#9132) administration. The minimum required number of enrolled patients suffering cancer pain was determined to be 70 in S#9131 and 20 in S#9132. These studies had the same dose-titration protocol as the main endpoint, i.e., pain relief rate (PRR) defined as the rate of achieving adequate pain control (APC), as in prior oral oxycodone trials in Japan. In S#9131, PRR was 81.4% (95% confidence interval: 70.3-89.7%), therefore, the null hypothesis of PRR<70% was rejected using the binominal one-sided test (p=0.0217). In S#9132, PRR was 73.7% also surpassing 70%. Safety was also assessed in the same way as in prior trials. The majority of adverse effects were moderate or mild and recovered with no sequelae. As shown above, the injection was considered to be effective and safe in cancer pain treatment. The details of these trials, particularly the dose-titration protocol for achieving APC and route switching information, are expected to enhance injection convenience for prescribers.


Assuntos
Analgésicos Opioides/administração & dosagem , Dor do Câncer/tratamento farmacológico , Oxicodona/administração & dosagem , Idoso , Analgésicos Opioides/efeitos adversos , Analgésicos Opioides/uso terapêutico , Feminino , Humanos , Injeções Intravenosas , Injeções Subcutâneas , Japão , Masculino , Pessoa de Meia-Idade , Oxicodona/efeitos adversos , Oxicodona/uso terapêutico , Resultado do Tratamento
12.
Artigo em Inglês | MEDLINE | ID: mdl-27051524

RESUMO

BACKGROUND: This study was designed to evaluate the population pharmacokinetics (popPK) of penicillin G in patients with infective endocarditis and establish a dosage regimen based on pharmacokinetic data and clinical outcome. METHOD: Forty-six serum penicillin G samples from 25 individuals were analyzed using a nonlinear mixed-effects model. popPK were estimated using a one-compartment model. We created a receiver operating characteristic (ROC) curve for penicillin G efficacy and the ratio of its minimum concentration (Cmin)/minimum inhibitory concentration (MIC). Simulations were used to optimize the penicillin G dosage regimen using this ratio. RESULT: Estimated popPK were: CL (L/h) = 0.21 × creatinine clearance (CLcr) (mL/min), Vd (L) = 28.9. The areas under the ROC curves were 0.87 for clinical efficacy. The cut-off value of penicillin G Cmin/MIC was 60. The continuous administration of 1 million IU penicillin G/h was necessary to achieve a positive outcome for patients with normal renal function (CLcr ≥ 60 mL/min). CONCLUSION: Our findings suggest that population-based parameters are useful for evaluating penicillin G pharmacokinetics and that an individualized dosage should be determined based on a described dosage regimen.

13.
Yakugaku Zasshi ; 135(11): 1307-15, 2015.
Artigo em Japonês | MEDLINE | ID: mdl-26521880

RESUMO

The dose of a transdermal fentanyl patch is proportional to its application site area. Therefore, the absorption of fentanyl may decrease if the patch detaches, leading to insufficient analgesia. Sixteen healthy volunteers were enrolled in a study to investigate the appropriate application sites and clinical utility of three transdermal fentanyl patches available in Japan. Three placebos, Fentanyl 1-day (Fentos; Fen), Fentanyl 3-day (Durotep; Dur), and Generic Fentanyl 3-day (HMT) were administered using a crossover study design. The placebos were applied to 11 different sites, including both sides of the upper arm, abdomen, back, thigh, chest, and the middle of the chest. We determined the patch detachment area and incidence of patch-induced itching every 24 h and evaluated differences between each application site using the Wilcoxon signed-rank test. Significant patch detachment was observed on the abdomen and upper arms with Fen, on the abdomen and chest with Dur, and on the chest with HMT compared with that at other sites (p<0.005). Although no significant difference in itching was observed between regions when administering Fen, itching significantly increased on the chest and back when using Dur and on the abdomen when using HMT as compared with that at other sites (p<0.05). Our results indicate that the three transdermal Fen patches exhibit different adhesive properties and local adverse events, indicating that the application site should be cautiously selected for each patch type.


Assuntos
Analgésicos Opioides/administração & dosagem , Fentanila/administração & dosagem , Administração Cutânea , Adulto , Estudos Cross-Over , Feminino , Humanos , Masculino , Pele/efeitos dos fármacos , Adesivo Transdérmico , Adulto Jovem
14.
J Pain Palliat Care Pharmacother ; 28(4): 338-50, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25359452

RESUMO

ABSTRACT In Japan, Oxycodone hydrochloride injection formulation has been approved in 2012. However, its pharmacokinetics has been poorly studied. The aim of this study is to evaluate the pharmacokinetics of oxycodone after intravenous and subcutaneous administration of oxycodone hydrochloride injection in Japanese patients with cancer pain. Noncompartmental analysis and population pharmacokinetic analysis were performed. We conducted a multicenter open-label study of oxycodone hydrochloride administered as constant infusion with the dose titrated individually according to the pain intensity in patients with cancer pain. Pharmacokinetic parameters for plasma oxycodone and its metabolites were estimated using pharmacokinetics of oxycodone was evaluated using a total of 344 plasma concentrations obtained from 89 patients. The estimated geometric mean clearance (CL) of oxycodone was 24.3 L per hour after constant intravenous infusion and 29.5 L per hour after constant subcutaneous infusion, respectively. Population pharmacokinetic analysis indicated that body surface area was the influencing factor on CL and there were no pharmacokinetic differences for CL between intravenous and subcutaneous infusion. These results provide important information for the clinical use of oxycodone injection.


Assuntos
Analgésicos Opioides/administração & dosagem , Analgésicos Opioides/farmacocinética , Neoplasias/complicações , Oxicodona/administração & dosagem , Oxicodona/farmacocinética , Dor/sangue , Dor/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Analgésicos Opioides/sangue , Analgésicos Opioides/uso terapêutico , Povo Asiático , Humanos , Infusões Intravenosas , Infusões Subcutâneas , Masculino , Pessoa de Meia-Idade , Neoplasias/sangue , Oxicodona/sangue , Oxicodona/uso terapêutico , Dor/complicações
15.
Gan To Kagaku Ryoho ; 41(4): 471-3, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24743363

RESUMO

In Europe and the United States, D9-tetrahydrocannabinol(THC, dronabinol), one of the psychoactive constituents of cannabis, has been used for both its anti-emetic and orexigenic effects in cancer patient receiving chemotherapy.However, dronabinol has not yet been launched in the market in Japan.In the future, it is necessary to ascertain the pharmacokinetics of dronabinol in cancer paitient.Therefore, we developed an HPLC procedure using electrochemical detection(ECD)for quan- titation of the concentrations of dronabinol in blood.An eluent of 50mM KH2PO4/CH3CN(9:16)was used as the mobile phase.The column was used the XTerra®RP18, and the voltage of the electrochemical detector in dronabinol was set at 400 mV.As a result, the calibration curve was linear in the range of 10 ng/mL to 100 ng/mL(y=964.85x -3,419, r=0.997).The lower limit of quantification was 0.5 ng/mL(S/N=3).The relative within-runs and between-runs standard deviations for the assay dronabinol were less than 4.7%. The method reported here is superior to previously reported methods in cancer patient.


Assuntos
Antieméticos/sangue , Cromatografia Líquida de Alta Pressão/métodos , Dronabinol/sangue , Técnicas Eletroquímicas/métodos , Humanos , Limite de Detecção , Reprodutibilidade dos Testes
16.
J Pain Palliat Care Pharmacother ; 26(3): 220-5, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22973910

RESUMO

Oxycodone is an opioid widely prescribed to cancer patients for pain relief. However, the pharmacokinetics of oxycodone has not been sufficiently examined. Therefore the aim of this work was to study population pharmacokinetics of oxycodone in patients with cancer pain. The authors analyzed 108 serum oxycodone samples of 33 individuals with nonlinear mixed-effects model (NONMEM). Population pharmacokinetics was calculated using the one-compartment model of clearance, volume of distribution, bioavailability, absorption constant rate, and lag time. An exponential error model was used to determine interindividual variability and a relative error model was applied to assess residual variability. Population pharmacokinetics of oxycodone at the end point were as follows: CL(L/h) = 10.7 × [1 + (2 - Child-Pugh Classification)] (Class: A = 0, B = 1, C = 2); V(d) (L) = 193; k(a) (h(-1)) = 0.336; T(lag) (h) = 0.859; F (%) = 63.9. Interindividual variability was CL: 30.5%, V(d): 44.6%, and F: 37.0%, and residual variability was 16.2%. As the total clearance in patients with liver dysfunction (Child-Pugh class B) was reduced to 33.3%, serum concentration of oxycodone increased by 1.5. Therefore, it became clear that dose adjustments are essential when treating patients with liver dysfunction. These findings suggest that population parameters are useful for evaluating pharmacokinetics of oxycodone in patients with cancer pain.


Assuntos
Analgésicos Opioides/farmacocinética , Modelos Biológicos , Oxicodona/farmacocinética , Dor/tratamento farmacológico , Adulto , Idoso , Analgésicos Opioides/administração & dosagem , Analgésicos Opioides/uso terapêutico , Disponibilidade Biológica , Relação Dose-Resposta a Droga , Feminino , Humanos , Hepatopatias/fisiopatologia , Masculino , Pessoa de Meia-Idade , Neoplasias/fisiopatologia , Dinâmica não Linear , Oxicodona/administração & dosagem , Oxicodona/uso terapêutico , Dor/etiologia , Distribuição Tecidual
17.
J Pain Palliat Care Pharmacother ; 26(2): 98-104, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22764844

RESUMO

Determining the appropriate dose of transdermal fentanyl (TDF) for the alleviation of cancer pain requires determining the factors causing variations in serum fentanyl concentration after TDF treatment. The objective of this study was to identify these factors and incorporate them into a formula that can be used to predict serum fentanyl concentration after application of a TDF patch. Blood samples of cancer patients treated with a TDF patch for the alleviation of pain were collected at 24, 48, and 72 hours after application to evaluate population pharmacokinetics using the nonlinear mixed-effect model (NONMEM). Based upon this evaluation, Child-Pugh Score and use of a cytochrome P450 3A4 (CYP3A4) inducer were identified as the most significant factors in variations in serum fentanyl concentration and incorporated into the following Final Model formula: CL(fenta) (L/h) = 3.53 × (15 - Child-Pugh Score) × (1 + 1.38 × use or no use of CYP3A4 inducer). Bootstrap evaluation of the Final Model revealed a high convergence rate, suggesting that the model formula is a reliable and useful tool for determining TDF dose for the alleviation of cancer pain.


Assuntos
Analgésicos Opioides/farmacocinética , Fentanila/farmacocinética , Neoplasias/complicações , Dor/tratamento farmacológico , Administração Cutânea , Adulto , Idoso , Analgésicos Opioides/administração & dosagem , Analgésicos Opioides/uso terapêutico , Citocromo P-450 CYP3A/biossíntese , Relação Dose-Resposta a Droga , Indução Enzimática/efeitos dos fármacos , Feminino , Fentanila/administração & dosagem , Fentanila/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Biológicos , Dinâmica não Linear , Dor/etiologia , Fatores de Tempo , Adesivo Transdérmico
18.
Yakugaku Zasshi ; 131(1): 113-27, 2011 Jan.
Artigo em Japonês | MEDLINE | ID: mdl-21212621

RESUMO

The pain experienced by cancer patients can be managed in 70-90% of cases by the World Health Organisation protocol for cancer pain. However, cancer pain treatment in Japan is not sufficiently effective. To use medicine safely and effectively, various problems must be solved. Therefore, in this study, appropriate usage of cancer pain treatment was examined. We were able to use acetaminophen suppositories (800 mg each) in cancer pain patients. It was suggested that high serum concentrations of oxycodone and hydrocotarnine might be observed in geriatric patients or in the state of decreased hepatic blood flow, making dose adjustment is necessary for such patients. We also clarified that the conversion ratio from oral oxycodone to intravenous ocycodone/hydrocotarnine was 0.71±0.12. In addition, we clarified the pharmacokinetics of controlled-release oxycodone in patients with cancer pain. Moreover, the findings of our study indicate that in the steady state, the serum concentrations of fentanyl are not maintained at a constant level for 3 days following the use of transdermal fentanyl. We established a method of appropriately passing a nasal duct for sustained release of fine granules of morphine sulfate. Resolution of the clinical problems associated with cancer pain treatments is anticipated to allow the proper use of cancer pain treatments in Japan.


Assuntos
Analgésicos/administração & dosagem , Analgésicos/farmacocinética , Neoplasias/tratamento farmacológico , Dor/tratamento farmacológico , Cuidados Paliativos , Acetaminofen/administração & dosagem , Acetaminofen/farmacocinética , Vias de Administração de Medicamentos , Fentanila/administração & dosagem , Fentanila/farmacocinética , Humanos , Japão , Neoplasias/complicações , Oxicodona/administração & dosagem , Oxicodona/farmacocinética , Dor/etiologia
19.
Gan To Kagaku Ryoho ; 35(5): 797-802, 2008 May.
Artigo em Japonês | MEDLINE | ID: mdl-18487916

RESUMO

Oxinorm powder is a rapid-release preparation of oxycodone hydrochloride for oral administration recently marketed for the first time in Japan. Administration of a powdered drug through a nasal tube is known to involve the risk of tube obstruction by the drug. For narcotic preparations like oxinorm powder, it is desirable from the perspective of drug control, that the drug administered be unlikely to remain in the cup, syringe or catheter used, and that the drug be dispensable in precise amounts. The present study was undertaken to identify problems associated with administration of oxinorm powder through a nasal tube and to determine an appropriate method for its administration. First, the solubility of the powder in various solvents was evaluated macroscopically to select initially appropriate solvents. Then, the drug dissolved in each of these solvents was administered through 3 types of catheters with different raw materials and forms, to simulate drug administration through a nasal tube. Percent residual drug remaining on/within the cup, syringe, and catheter was measured by HPLC, to evaluate the adhesiveness of the drug. When dissolved in distilled water, black vinegar, or milk, the drug was easy to administer through the catheter, with a low percentage of drug remaining on the cup, syringe, and catheter, suggesting that these fluids can be used as solvents for oxinorm powder. Semidigested nutrients such as Ensure.H were found to be unsuitable solvents for oxinorm powder.


Assuntos
Analgésicos Opioides/administração & dosagem , Entorpecentes/administração & dosagem , Oxicodona/administração & dosagem , Solventes , Administração Oral , Humanos , Intubação Gastrointestinal , Pós
20.
Gan To Kagaku Ryoho ; 35(5): 803-8, 2008 May.
Artigo em Japonês | MEDLINE | ID: mdl-18487917

RESUMO

To examine the influence of drug therapy guidance by pharmacists on the use of a rescue dose (RD) for opioid analgesics (opioids) and pain as well as drug therapy guidance in cancer pain treatment, we conducted a patient satisfaction survey. The subjects were 56 cancer patients undergoing opioid therapy in hospitals belonging to the Symptom Control Research Group (SCORE-G). The survey period was 2 months (from November 1 until December 31, 2006). Drug therapy guidance regarding the use of RD was performed twice in each patient to evaluate the patients' satisfaction. RD was prescribed in 87.8% of the patients in the first guidance and in 80.5% in the second guidance periods. The proportion of patients who used RD significantly increased from 63.8% to 87.5%. Five items significantly improved in the second guidance period: "marked analgesic effects," "satisfaction with current treatment," "correct understanding of RD usage," "relief through RD," and "appropriate use of RD." On comprehensive evaluation following the second round of guidance, 81% of the patients reported overall satisfaction, and 78% reported the usefulness of guidance in pain treatment. These results suggest that positive guidance by pharmacists increases patients' satisfaction. In providing guidance, it was important to confirm the characteristics and side effects of opioids as well as the necessity of RD to patients accurately and repeatedly.


Assuntos
Analgésicos Opioides/administração & dosagem , Neoplasias/tratamento farmacológico , Satisfação do Paciente , Farmacêuticos , Relações Profissional-Paciente , Coleta de Dados , Humanos , Educação de Pacientes como Assunto
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