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We evaluated the drug 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 C0 and C2, respectively.A 53-year-old woman was receiving oral CsA (NeoralTM), 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 drug 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 drug interaction. Consequently, we were able to adequately control the CsA blood concentration without either graft rejection or any adverse effects.

PURPOSE. Infection control is particularly vital in hospitals, and proper use of antimicrobial drugs is one of the most important roles of hospital pharmacists. In this study, we surveyed patients who had been prescribed single-use ciprofloxacin (CPFX), and evaluated the blood concentration of CPFX from the predictive AUC (area under the concentration curve). METHODS. This study was performed retrospectively to 112 adult patients diagnosed as having respiratory infections who had been treated as inpatients with intravenous CPFX for more than 3 days at Toho University Omori Hospital in Tokyo. The predictive AUC of each patient was obtained from the modified formulae reported by Forrest et al. (1993) [1]. The relation between the antimicrobial activity of CPFX and pharmacokinetic/pharmacodynamic (Cmax, AUC and AUC/MIC (minimum inhibitory concentration)) was studied. RESULTS. Although CPFX is excreted from the kidney, standard treatment with this drug does not take renal function into consideration. Our results indicated that CPFX was effective in less than 50% of the patients who received it. Moreover, the AUC/MIC ratio in both the effective group and the failure group was less than 125 when the clinical target was gram-negative bacteria. CONCLUSION. These results suggest that the clinical use of CPFX for the treatment of infectious diseases does not reach the target AUC/MIC ratio, and that the concentration of CPFX is not within the range to which many pathogens are susceptible in a large proportion of patients. To ensure the effective treatment of patients with infectious diseases and to prevent the development of resistance in bacteria, we recommend therapeutic drug monitoring (TDM) of CPFX in hospitals.