Search

Background: Bucolome is a non-steroidal anti-inflammatory drug and uricosuric agent, currently used only in Japan. It is known to induce drug interactions by inhibiting cytochrome P450 (CYP) 2C9. It is often used to enhance the anticoagulant effect of warfarin by utilizing its drug interactions. There are only a few reports on drug interactions of bucolome and the mechanism remain poorly understood. Case presentation: An 81-year-old woman with a history of type 2 diabetes mellitus was taking glimepiride 2 mg/day and voglibose 0.6 mg/day. After hospitalization, the patient underwent surgical aortic valve replacement surgery (day 0). Glimepiride and voglibose were resumed on the second postoperative day (day 2), and warfarin was started to prevent thromboembolism. Since the prothrombin time-international normalized ratio on day 9 was low at 1.24, 300 mg/day of bucolome was added to enhance the effect of warfarin. A gradual decrease in blood glucose levels was observed from the day after bucolome administration was initiated. Hypoglycemia in the 56–57 mg/dL range occurred before lunch and dinner on the 6th day (day 14) of bucolome administration, due to which voglibose was discontinued. Hypoglycemia below 70 mg/dL was not observed thereafter, and the general condition of the patient was stable. Conclusions: Based on the clinical course and literature review, we believe that hypoglycemia in the present case was due to a drug interaction, caused by inhibition of CYP2C9 by bucolome and competitive inhibition of CYP2C9 by warfarin, which affected the pharmacokinetics of glimepiride. The possibility of hypoglycemia due to drug interactions should be considered by physicians, when bucolome is included to enhance the effect of warfarin, in patients taking glimepiride. [ABSTRACT FROM AUTHOR]

Background: Magnesium oxide (MgO) is often co-prescribed with L-dopa/carbidopa (LDCD) to improve constipation in Parkinson's disease patients. The mixing of L-dopa and MgO has been shown to degrade L-dopa; however, there is no interaction study on humans. We proposed mechanisms for the interaction between LDCD and MgO and conducted pharmacokinetic studies on rats and humans. To assess pharmacodynamic changes with the MgO treatment, we applied a model-based meta-analysis (MBMA).Methods: The effects of MgO on the stabilities of L-dopa and carbidopa were evaluated in in vitro studies. We conducted pharmacokinetic interaction studies of MgO and LDCD on rats and healthy volunteers. A clinical study was conducted with an open-label, non-randomized, single-arm, and two-phase study. In MBMA, we constructed a population pharmacokinetic/pharmacodynamic model of L-dopa and predicted the effects of the MgO treatment on the pharmacodynamics of L-dopa.Results: In vitro results suggested that carbidopa was unstable under alkaline pH conditions. Reductions in plasma LDCD concentrations were observed after oral-MgO/oral-LDCD, but not in oral-MgO/i.v.-LDCD treatments in rats, suggesting that the gastrointestinal tract is an interaction site. A healthy volunteer study showed that MgO was also associated with significant decreases of 35.3 and 80.9% in the AUC0-12 of L-dopa and carbidopa, respectively. A model-based simulation suggested that the MgO treatment was undesirable for the effectiveness of L-dopa.Conclusions: This is the first study to show a clear pharmacokinetic interaction between LDCD and MgO in humans. Further investigations to confirm the effects of MgO on the pharmacodynamics of L-dopa are required. [ABSTRACT FROM AUTHOR]