Objective.To study the possible relationship between whole-blood hydroxychloroquine (HCQ) concentrations and clinical efficacy of HCQ in patients with systemic lupus erythematosus (SLE).Methods. Whole-blood HCQ concentrations were measured, under blinded conditions, in 143 unselected patients with SLE who had been receiving HCQ 400 mg daily for at least 6 months. The relationship of these concentrations to current disease activity and to subsequent exacerbations during 6 months of followup was investigated.Results. At baseline, 23 patients had active disease (mean ؎ SD SLE Disease Activity Index 12.4 ؎ 7.5). The mean whole-blood HCQ concentration in this group was significantly lower than that in the 120 patients with inactive disease (694 ؎ 448 ng/ml versus 1,079 ؎ 526 ng/ml; P ‫؍‬ 0.001). Among the 120 patients who had inactive disease at baseline, the mean HCQ concentration at baseline in the 14 (12%) who had disease exacerbations during followup was significantly lower than that in the patients whose disease remained inactive. Multivariate logistic regression showed that the HCQ concentration was the only predictor of exacerbation (odds ratio 0.4 [95% confidence interval 0.18-0.85], P ‫؍‬ 0.01). Receiver operating characteristic curve analysis showed that a whole-blood HCQ concentration cutoff of 1,000 ng/ml had a negative predictive value of 96% for exacerbation during followup.Conclusion. Low whole-blood HCQ concentrations are associated with SLE disease activity and are a strong predictor of disease exacerbation. Regular drug assaying and individual tailoring of treatment might help to improve the efficacy of HCQ treatment in patients with SLE.

Morphine is widely used to treat moderate to severe postoperative pain. The goal of this study was to characterize the pharmacodynamics of morphine-induced analgesia during intravenous morphine titration in the immediate postoperative period and to evaluate sedation occurrence according to morphine dose in this setting. Two hundred and twenty-eight patients undergoing major orthopedic surgery were included. They received intravenous (iv) morphine titration in the post-anesthesia care unit as boluses of 2 or 3 mg, every 5 min until analgesia was established. Pain was assessed using visual analogue scale (VAS) scores. Morphine analgesia-time data were analysed via a kinetic-pharmacodynamic population approach using non-linear mixed-effect modeling NONMEM. Sedation was assessed by the Ramsay score with scores >2 representing clinically significant sedation. The relationship between sedation occurrence and morphine dose was modeled using logistic regression. Morphine pharmacodynamic was best described by an indirect response model with an inhibitory function affecting pain onset, and it showed that decreasing delay between extubation and titration, decreasing initial VAS and intra-operative non-steroidal anti-inflammatory drug resulted in increased morphine potency. Logistic regression showed that a morphine dose of 20 mg was associated with a high likelihood of sedation occurrence. Our study supported the possibility of modeling the time course of a complex response in the absence of pharmacokinetic data. The current data should lead to a more rational management of the immediate postoperative pain.