薬理と治療
Volume 38, Issue 2, 2010
Volumes & issues:
-
REVIEW
-
-
未承認薬のコンパッショネート使用─日本において患者のアクセスの願いにどう応えるか─
38巻2号(2010);View Description Hide DescriptionCompassionate use(CU)is commonly known as limited supply of unapproved drugsto patients who suffer from life-threatening or chronically debilitating diseases for whomauthorized therapies have failed or do not exist and who cannot enter clinical trials. In drugregulation, CU casts very tough but relevant questions on its application; the trade-offbetween patients’ free access to such medications, on the one hand, and safeguarding thepatient and ensuring the continued integrity of the scientific process that collect data in randomizedcontrolled trial, on the other. Although some developed countries already have systemsfor CU as exceptional measures, Japan does not have yet. Consequently, the recentincrease in the personal imports of unapproved medicines has become a serious social problemwhich has awakened Japanese to the need for a kind of risk management. Inasmuch asone third of Japanese die due to cancer, many cancer patients want greater access to unapproveddrugs through CU. So the introduction of a system for CU in Japan is a matter ofutmost urgency. We reviewed the history and status of implementation of CU in the USA,Europe, and our neighboring country, Korea. We also reviewed Japanese history on the supplyof unapproved drugs for intractable diseases on humanitarian grounds in limited therapeuticareas. We showed our points of view, specifically, how we can meet the demands ofJapanese patients with intractable diseases. We believe this review will make a great contributionabout planning and developing the regulatory system for CU in Japan.KEY WORDSCompassionate use, Unapproved drugs, System introduction to Japan, Drug regulation
-
-
ORIGINAL ARTICLES
-
-
宮古ビデンスピローサの鉄欠乏性貧血と塩酸/エタノール誘発胃粘膜障害に対する効果
38巻2号(2010);View Description Hide DescriptionBackground Bidens pilosa L. var. radiata SCHERFF is a variation of Bidens pilosa. The plantwas cultivated on Miyako Island, Okinawa prefecture, Japan, and its aerial parts were harvested,named MMBP. As MMBP contained minerals in abundance, we investigated the effects ofMMBP against iron−deficiency anemia and fatigue from anemia. Moreover, we examined theeffect of MMBP on experimental gastric mucosal injury, as anti−inflammatory activity ofMMBP was evident.Methods An iron−deficiency anemia model was induced by administration of an iron−deficientdiet to rats for 2 weeks. Rats in the MMBP group were orally administered an irondeficientdiet containing MMBP and the rats were given exercise tolerance, swimming for 10min. Moreover, male ICR mice were orally administered HCl/EtOH solution and gastricmucosal injury was then induced. MMBP and cimetidine were orally administered 1 h beforetreatment with HCl/EtOH solution. The mucosal lesions were for photographed.Results Compared with the control group, MMBP group significantly increased blood lowhemoglobin(Hb)level induced by the iron−deficient diet under non−tolerance condition.MMBP significantly decreased serum lactic acid(LA)level and alanine aminotransferase(ALT)levels under forced swim−tolorance. MMBP also improved the inflammatory area ongastric mucosa. This suggested that MMBP was effective against iron−deficiency anemia andgastric mucosal injury.Conclusions Iron preparation for anemia is known to cause gastric mucosal injury as a sideeffect. MMBP improved anemia and gastric mucosal injury. Therefore, MMBP has potentialas supplement for both iron−deficiency anemia and gastric mucosal injury.(Jpn Pharmacol Ther 2010;38:157−63)KEY WORDS Bidens pilosa, Anemia, Gastric mucosal injury, Supplement -
Long−term Usefulness of Aprindine Hydrochloride in Elderly Patients
38巻2号(2010);View Description Hide DescriptionBackground Aprindine is a Vaughan−Williams Class Ib antiarrhythmic drug with a weaknegative inotropic effect. It is unnecessary to adjust its dose even in patients with renalimpairment because it is metabolized in the liver, suggesting its usefulness in elderlypatients. However, few reports are available on its safety and blood concentration duringlong−term treatment in elderly patients.Objectives This study conducted on elderly patients with tachyarrhythmia who weretreated with aprindine for a long time period and investigated aprindine concentration inblood and its effect on cardiac function.Methods Thirty outpatients with symptomatic supraventricular or ventricular arrhythmiawere enrolled. Aprindine was administered at 40 mg/day b. i. d. Blood concentration wasmeasured before and 2 hours after morning medication at 6 months.Results Of the study population, 8 patients were withdrawn from the study. In the remaining22 patients, aprindine concentrations in blood were measured at 218±115 days(max. 504days;before morning medication)and 213±135 days(max. 518 days;2 hours after morningmedication). The time course of aprindine concentration in blood was stable. No significantdifference in the blood concentration was found between the elderly(≧65 years of age)andnon−elderly (<65 years) patients, which suggested that aging had no influence on theincreased aprindine level in blood concentration. Among the 14 patients with paroxysmalatrial fibrillation, 13 patients maintained sinus rhythm during the treatment. Twenty−fourhourECG monitoring showed that aprindine significantly reduced supraventricular and ventricularpremature contractions without any influence on heart rates.Conclusions The number of elderly patients with arrhythmias is increasing in an agingsociety. Aprindine can be safely administered to such patients receiving long−term treatment.(Jpn Pharmacol Ther 2010;38:165−71)KEY WORDS Aprindine, Elderly patient, Long−term, Concentrations -
2 型糖尿病患者における血圧と尿中アルブミンに対するイルベサルタン単独療法とシルニジピンとの併用療法の有効性
38巻2号(2010);View Description Hide DescriptionIn 2008, irbesartan(IRBETAN_Tablet), an angiotensin II receptor blocker(ARB),became available in Japan. Diabetic nephropathy is one of the main causes of death in diabeticpatients. Irbesartan is reported to reduce blood pressures as well as albuminuria in hypertensivediabetic patients in Western countries, but little information is available in Japan. Thepurpose of this study is to investigate the effect of irbesartan as monotherapy, or in combinationwith cilnidipine on blood pressures, albuminuria and adverse reactions in Japanese hypertensivediabetic patients.Thirteen patients with hypertension and type 2 diabetes(male n=9, female n=4)werestudied for irbesartan monotherapy. Twenty six patients with hypertension and type 2 diabetes(male n=13, female n=13)were studied for combination therapy with irbesartan andcilnidipine. All patients were under stable glycemic control. All patients had normal liverfunctions. Systolic(SBP)and diastolic(DBP)blood pressures were measured, and albuminuriawas assessed with urinary albumin excretion index(UAI, mg/g creatinine, normal range<30mg/g creatinine).Irbesartan(100 mg/day after breakfast)was administered over 12 weeks. It significantlyreduced SBP by 17.6%(153→126 mmHg), DBP by 13.4%(82→71 mmHg), and UAI by52.8%(180→85 mg/g creatinine). Irbesartan(100 mg/day after breakfast)and cilnidipine(10 mg/day after breakfast)was administered over 12 weeks. It significantly reduced SBP by22.6%(164→127 mmHg), DBP by 15.3%(87→65 mmHg), and UAI by 70.2%(322→96 mg/g creatinine). HbA1c was not changed before and after the treatment. Serum ALT, AST,γ−GTP, uric acid, potassium and creatinine were not changed before and after the treatment,and no adverse reactions were observed over the study period.It is concluded that irbesartan monotherapy is effective to reduce not only blood pressuresbut also albuminuria in Japanese hypertensive diabetic patients. In addition, combinationtherapy with irbesartan and cilnidipine is more effective. Irbesartan is suggested to protectdiabetic nephropathy because of its great reduction of albuminuria.(Jpn Pharmacol Ther 2010;38:173−8)KEY WORDS Irbesartan, Microalbuminuria, Macroalbuminuria, Diabetic nephropathy,Hypertension, Cilnidipine -
血液透析施行中の腎性貧血に対する無血清培養にて製造された遺伝子組換えヒトエリスロポエチン製剤(エポエチン カッパ)の第II/III相二重盲検比較試験
38巻2号(2010);View Description Hide DescriptionObjectives The objectives of this randomized, multi−center, double blind, comparativestudy were to confirm the equivalent efficacy and compare the safety of epoetin kappa andepoetin alpha in renal anemia patients on hemodialysis.Method The patients receiving epoetin alpha were randomized to epoetin alpha or epoetinkappa administered intravenously at the same dose under double−blind conditions for 24weeks. The primary endpoint was mean change in hemoglobin(Hb)value, while the secondaryendpoints were mean Hb, target Hb maintenance rate(the proportion of subjects whoseHb was within the target Hb range), mean weekly dose, and the percentage of patientswhose dose changed.Results Mean change in Hb value was 0.13±0.73 g/dL(mean±SD)in the epoetin kappagroup, and 0.08±0.81 g/dL in the epoetin alpha group, for a difference of 0.05 g/dL(twosided95% confidence interval:−0.12 to 0.22). As a result, equivalent therapeutic efficacyof both epoetin kappa and epoetin alpha was demonstrated. All of the secondary endpointsshowed equivalent efficacy between these two groups. Safety profiles of epoetin kappa andepoetin alpha were similar, and no antibodies in both groups were detected.Conclusions Equivalent therapeutic efficacy of epoetin kappa and epoetin alpha was confirmed,and comparable anemia improvements to epoetin alpha were demonstrated. In addition,a similar safety profile to epoetin alpha was also demonstrated.(Jpn Pharmacol Ther 2010;38:181−98)KEY WORDS Erythropoietin, Epoetin kappa, Renal anemia patients, Hemodialysis, Double−blind study -
血液透析施行中の腎性貧血に対する無血清培養にて製造された遺伝子組換えヒトエリスロポエチン製剤(エポエチン カッパ)の長期投与試験
38巻2号(2010);View Description Hide DescriptionObjectives The objectives of this study were to evaluate safety and efficacy of long−termtreatment with epoetin kappa in renal anemia patients receiving hemodialysis.Method Subjects with renal anemia on hemodialysis receiving a recombinant humanerythropoietin(rHuEPO)treatment were switched from their rHuEPO(epoetin alpha or epoetinbeta)to the same weekly dose of epoetin kappa administered intravenously for 52weeks, with their dosage and dosing frequency adjusted to keep within a target hemoglobin(Hb)range(10.0 g/dL to 12.0 g/dL)wherever possible. Efficacy endpoints were;target Hbmaintenance rate(the proportion of subjects whose hemoglobin value was within the targetHb range), mean Hb change, and mean weekly dose change.Results The target Hb maintenance rate was 91.6% at baseline, 83.0% at Week 12, 83.3%at Week 28 and 85.1% at Week 52, changing in the range of 78.4 to 92.4% throughout thetreatment period. There were no great changes in target Hb maintenance rates, and mean Hbvalues were well maintained. Additionally, no great change in either mean Hb values, ormean weekly doses were observed. In safety assessments, adverse events incidences werenearly identical throughout the treatment period, and no clinically significant adverse drugreaction was noted. Nor were any antibodies to either treatment detected.Conclusions Target Hb maintenance rates were good throughout 52 weeks of treatmentperiod, while sustained, stable improvements in anemia were shown. No clinically significantadverse drug reaction was noted with the long−term epoetin kappa administration.(Jpn Pharmacol Ther 2010;38:199−212)KEY WORDS Erythropoietin, Epoetin kappa, Chronic renal failure patients, Hemodialysis,Long−term clinical study
-