Drug interaction between methotrexate and salazosulfapyridine in Japanese patients with rheumatoid arthritis.

BACKGROUND: Methotrexate (MTX) and salazosulfapyridine (SASP) are disease-modifying drugs that are commonly used in the treatment of rheumatoid arthritis (RA), and combination therapy with MTX and SASP is recommended for RA patients who show an inadequate response to monotherapy with either drug. This study was designed to examine the interaction between the two drugs from the viewpoint of serum MTX concentration in Japanese RA patients, who were receiving combination therapy with relatively low doses of MTX and SASP. METHODS: This is a 24-week open-label intervention study of stable RA patients (n = 10) with low disease activity. In these patients, who had received SASP/MTX combination therapy for at least 12 weeks, SASP was discontinued, and the patients received MTX monotherapy for the next 24 weeks. The primary outcome was change of serum MTX concentration at 12 weeks after discontinuation of SASP. Two disease activity markers, simplified disease activity index (SDAI) and disease activity score-C reactive protein (DAS28-CRP), were assessed as secondary outcomes at 24 weeks after discontinuation of SASP. We also monitored levels of matrix metalloproteinase-3 (MMP-3) and inflammatory cytokines. Patients were asked to complete a questionnaire after the study. RESULTS: Serum MTX concentration in RA patients who discontinued SASP increased more than 2-fold within 4 weeks, and the higher level was maintained thereafter. No significant differences were detected in SDAI, DAS28-CRP, MMP-3 or inflammatory cytokines. Most participants reported no change in physical condition after withdrawal of SASP, and most preferred MTX monotherapy for future treatment. CONCLUSIONS: Withdrawal of SASP from patients receiving SASP/MTX caused a rapid, marked increase of serum MTX concentration, without any apparent change in disease parameters or side effects. Our results suggest that SASP can be discontinued without adverse effects in stable RA patients receiving combination therapy, at least among Japanese patients receiving relatively low doses of the two drugs. TRIAL REGISTRATION: UMIN000024507. October 21, 2016 retrospectively registered.

Effect of switching basal insulin regimen to degludec on quality of life in Japanese patients with type 1 and type 2 diabetes mellitus.

BACKGROUND: Maintainance of a stable basal insulin level is important for glycemic control in treatment of diabetes mellitus. Recently introduced insulin degludec has the longest duration of action among basal insulin formulations. The purpose of this study was to assess changes in quality of life (QOL) associated with switching the basal insulin regimen to degludec in patients with type 1 and type 2 diabetes mellitus. METHODS: This 24-week open-label intervention study included type 1 (n = 10) and type 2 (n = 20) diabetes mellitus patients, with adequately controlled hemoglobin A1c (HbA1c), who had received insulin glargine or detemir for at least 6 months. The primary outcome was change of QOL from baseline, as assessed by the Diabetes Therapy-Related QOL (DTR-QOL) application, after switching from glargine or detemir to degludec. HbA1c and other parameters were also assessed as secondary outcomes. RESULTS: QOL and HbA1c in patients with type 1 diabetes mellitus were unchanged during this study. In patients with type 2 diabetes mellitus, HbA1c did not change, but total DTR-QOL score was significantly improved from baseline after switching to degludec. The DTR-QOL Factor 2, "Anxiety and dissatisfaction with treatment", was significantly improved in patients with type 2 diabetes mellitus and especially in the subgroup receiving basal supported oral therapy (BOT). CONCLUSIONS: Switching of the basal insulin regimen from glargine or detemir to degludec significantly improved the QOL of patients with type 2 diabetes mellitus who were receiving BOT, by reducing mental stress or anxiety about their treatment.

[Improvement of epirubicin-induced phlebitis to switch from liquid preparation to lyophilized formulation].

Adjuvant chemotherapy containing epirubicin is commonly used to treat patients with pre- or post-operative breast cancer. It is known that the epirubicin(FarmorubicinRTU)preparation often caused phlebitis, whereas dexamethasone has been used to prevent that reaction. We examined whether the lyophilized formulation of epirubicin(Farmorubicin)can reduces the incidence of phlebitis compared with the preparation. All infusions were administered through a peripheral vein. Adverse drug reaction including phlebitis was evaluated after each infusion and at the subsequent visit to four or six cycles. Sixty-two patients were given the preparation and 35 the lyophilized formulation. Epirubicininduced phlebitis was observed in 45.7% of patients given the preparation and in 48.4% of those given the lyophilized formulation. There was no statistically significant difference between the two groups(p=0.41). However, the incidence of severe phlebitis requiring treatment with steroid ointment was significantly increased among patients treated with the preparation(27.4% vs 9.7%, p<0.05, respectively). There was no significant difference in the incidence of adverse drug reactions other than severe phlebitis between the two groups. In this study, lyophilized formulations of epirubicin significantly reduced the incidence of severe phlebitis compared with that among patients receiving the preparation. Using lyophilized formulations of epirubicin should be considered to prevent a reduction in QOL with epirubicin-induced phlebitis in patients with breast cancer.

[Consideration of preventive free-flowing IV infusion method for vinorelbine].

Vinorelbine is administered to treat solid tumors such as non-small cell lung cancer and breast cancer, and good treatment results have been reported. Although this agent is known to cause phlebitis, some studies indicated that its administration over 5 minutes or less decreased the incidence of this adverse effect to approximately 5%. However,most studies employed bolus injection, and no study has reported completing drip infusion within 5 minutes. In the present study,we investigated the preventive effects on phlebitis of administering this agent over 5 minutes or less by drip infusion,which is simpler and more useful than intravenous injection. We administered vinorelbine 35 times to 6 patients with breast cancer or non-small cell lung cancer. The mean administration period was 3 minutes and 59 seconds +/-22 seconds, and the incidence of phlebitis was 5.7%. Our administration method involving drip infusion prevented phlebitis as markedly as by intravenous injection. In addition,there were no marked differences in the incidences of adverse effects other than phlebitis. The administration method employed in this study (drip infusion within five minutes) prevented vinorelbine-induced phlebitis, and was simpler than intravenous injection.

Influence of cytarabine and cyclophosphamide on the disposition kinetics of cyclosporin A after bone marrow transplantation.

The blood concentration of cyclosporin A (CyA) often gradually increases or is unstable in the early period of immunotherapy in bone marrow transplantation patients. In the protocol for bone marrow transplantation, pretreatment with cytarabine (Ara-C) and cyclophosphamide (CPA) is employed. We examined the influence of Ara-C and CPA on the disposition kinetics of CyA, in using rats to define the mechanism for the observation. Rats were intravenously administered daily with Ara-C (120 mg/kg/day) or CPA (60 mg/kg/day) intravenously for 2 days and were then intravenously given CyA (10 mg/kg). The blood concentration of CyA after intravenous administration of CyA at 1 day after the last administration of CPA was significantly lower and the total clearance was significantly larger than those in the vehicle control rats, while the blood concentration and the pharmacokinetic parameters of CyA were unchanged after Ara-C treatment. The expression of mdr1a, mdr1b, and CY3A2 mRNAs, and the levels of the corresponding proteins in the liver were increased after the CPA treatment. These CPA-induced changes were almost fully reversed to the control levels by 2 weeks. Thus, our results indicate that the decrease of blood CyA concentration induced is a consequence of the induction of P-glycoprotein and CYP3A in the liver by the CPA treatment, and these changes are reversed within 2 weeks after the transplantation.