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Population Pharmacokinetics of Hydroxychloroquine in Japanese Patients With Cutaneous or Systemic Lupus Erythematosus.

Abstract：

BACKGROUND:Hydroxychloroquine (HCQ) is an effective treatment for patients with cutaneous lupus erythematosus (CLE) or systemic lupus erythematosus (SLE) and has been used for these patients in more than 70 nations. However, in Japan, HCQ has not been approved for CLE or SLE. To establish an appropriate therapeutic regimen and to clarify the pharmacokinetics (PK) of HCQ in Japanese patients with CLE with or without SLE (CLE/SLE), a population pharmacokinetic (PopPK) analysis was performed. METHODS:In a clinical study of Japanese patients with a diagnosis of CLE irrespective of the presence of SLE, blood and plasma drug concentration-time data receiving multiple oral doses of HCQ sulfate (200-400 mg daily) were analyzed using nonlinear mixed-effects model software. The blood and plasma concentrations of HCQ were analyzed using a high-performance liquid chromatography tandem mass spectrometry method. Model evaluation and validation were performed using goodness-of-fit (GOF) plots, visual predictive check, and a bootstrap. RESULTS:The PopPKs of HCQ in the blood and plasma of 90 Japanese patients with CLE/SLE were well described by a 1-compartment model with first-order absorption and absorption lag time. Body weight was a significant (P < 0.001) covariate of oral clearance of HCQ. The final model was assessed using GOF plots, a bootstrap, and visual predictive check, and this model was appropriate. Simulations based on the final model suggested that the recommended daily doses of HCQ sulfate (200-400 mg) based on the ideal body weight in Japanese patients with CLE/SLE were in the similar concentration ranges. CONCLUSIONS:The PopPK models derived from both blood and plasma HCQ concentrations of Japanese patients with CLE/SLE were developed and validated. Based on this study, the dosage regimens of HCQ sulfate for Japanese patients with CLE/SLE should be calculated using the individual ideal body weight.

journal_name

Ther Drug Monit

journal_title

Therapeutic drug monitoring

authors

Morita S,Takahashi T,Yoshida Y,Yokota N

doi

10.1097/FTD.0000000000000261

subject

Has Abstract

pub_date

2016-04-01 00:00:00

pages

259-67

issue

eissn

0163-4356

issn

1536-3694

journal_volume

pub_type

杂志文章

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Population Pharmacokinetics of Hydroxychloroquine in Japanese Patients With Cutaneous or Systemic Lupus Erythematosus.