Vol.21 No.1

Original Article

Therapeutic drug monitoring of cyclosporine microemulsion in interstitial pneumonia with dermatomyositis

Authors

Koji Nagai¹ , Tohru Takeuchi¹ , Takuya Kotani¹ , Kenichiro Hata¹ , Shuzo Yoshida¹ , Kentaro Isoda¹ , Youhei Fujiki¹ , Hideyuki Shiba¹ , Shigeki Makino¹ , Toshiaki Hanafusa¹

Received:

27 January 2010

Accepted:

6 July 2010

Published online:

4 August 2010

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Abstract

The prognosis of dermatomyositis (DM)-associated progressive interstitial pneumonia (IP) has recently been improved by steroids/cyclosporine-A (CSA) combination therapy, but treatment outcomes varied. One reason for this variation is thought to be differences in CSA regimen. There is marked interpatient variability in CSA absorption. However, the pharmacokinetics of CSA has rarely been studied. In this study, we calculated the area under the blood concentration-time curve (AUC) of CSA microemulsion in 15 patients with progressive IP complicating DM, and analyzed its correlation with CSA levels at blood sampling time points to investigate the optimum monitoring and dosing regimen. The highest correlation between AUC_0-6 and blood level of CSA was observed 2 h (C2) after drug administration (R = 0.910). The trough level (C0) was not correlated with AUC_0-6 (R = 0.052). There were no differences in blood levels (AUC_0-6, C2, and C6) between postprandial administration in a divided dose (CSA given twice daily) and preprandial administration once daily in a single dose, while C0 was significantly lower (P = 0.020) when the drug was administered once daily before breakfast. These findings suggest that measurement of CSA blood level, especially C2 and C0, is useful to monitor clinical and adverse effects of CSA during combination therapy. It is also suggested that preprandial, once daily administration of CSA is beneficial in DM patients with progressive IP.

Key words

Cyclosporine - Dermatomyositis - Interstitial pneumonia - Monitoring