title: Therapeutic drug monitoring of cyclosporine microemulsion in interstitial pneumonia with dermatomyositis.
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.
authors.affiliation: First Department of Internal Medicine, Osaka Medical College, 2-7 Daigaku-Machi, Takatsuki, Osaka, 569-8686, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Nagai
authors.forename: Tohru
authors.initials: T
authors.lastname: Takeuchi
authors.forename: Takuya
authors.initials: T
authors.lastname: Kotani
authors.forename: Kenichiro
authors.initials: K
authors.lastname: Hata
authors.forename: Shuzo
authors.initials: S
authors.lastname: Yoshida
authors.forename: Kentaro
authors.initials: K
authors.lastname: Isoda
authors.forename: Youhei
authors.initials: Y
authors.lastname: Fujiki
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Shiba
authors.forename: Shigeki
authors.initials: S
authors.lastname: Makino
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Hanafusa
mesh_terms: D000368:Aged; D018501:Antirheumatic Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D019540:Area Under Curve; D016572:Cyclosporine / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D003882:Dermatomyositis / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D016903:Drug Monitoring / Q000379:methods; D004359:Drug Therapy, Combination; D004655:Emulsions; D005260:Female; D006801:Humans; D017563:Lung Diseases, Interstitial / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011241:Prednisone / Q000627:therapeutic use
chemical_list: D018501:Antirheumatic Agents; D004655:Emulsions; D016572:Cyclosporine; D011241:Prednisone