C2モニタリングによりシクロスポリンAとフルコナゾールおよびクラリスロマイシンとの薬物相互作用の検討を行った生体腎移植患者の一症例

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We evaluated the drag interaction between Cyclosporine A (CsA) and both fluconazole (FCZ) and clarithromycin (CAM) using absorption profiling monitoring in a renal transplant recipient. The concentrations at 0 hr and 2 hr after the administration were monitored as CO and C2, respectively. A 53-year-old woman was receiving oral CsA (Neoral^<TM>), methylpredonisolone, and mycophenolate mofetil. Oral FCZ was then added to this regimen for the treatment of oral Candidiasis. The next day, the patients C0/D and C2/D ratios increased 1.6 and 2.4-fold, respectively. Moreover, the CsA clearance decreased by approximately 45%. After altering the administration routes and drug combinations (intravenous FCZ and intravenous CsA, intravenous FCZ and oral CsA), the CsA clearance decreased to 30% of the baseline. These results suggest that FCZ appears to inhibit both the liver and intestinal function by means of the cytochrome P450 system, thereby increasing the bioavailability of CsA. Ten days later, the patient received the concomitant oral administration of CAM for an H. pylori infection. The C0/D and C2/D ratios increased by approximately 3-fold and the CsA clearance decreased by 35%, but these pharmacokinetic parameters normalized within a few days of initiating coadministration. The drag interaction between CsA and CAM may inhibit liver metabolism of CsA. Therefore, the mechanisms responsible for FCZ and CAM interaction with CsA differ. Our findings show that monitoring the C0 and C2 levels was useful in determining the CsA absorption profile, which allowed for a detailed evaluation of drag interaction. Consequently, we were able to adequately control the CsA blood concentration without either graft rejection or any adverse effects.
日本医療薬学会の論文
2003-12-10

C2モニタリングによりシクロスポリンAとフルコナゾールおよびクラリスロマイシンとの薬物相互作用の検討を行った生体腎移植患者の一症例

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