Pharmacokinetic and Pharmacodynamics of Self-Assembled Cubic Liquid Crystalline Nanoparticle Gel After Transdermal Administration.

BACKGROUND The aim of this study was to assess the pharmacokinetics after transdermal administration by a novel skin microdialysis technology in rats. The guinea pig model was established by investigating the pharmacodynamics. MATERIAL AND METHODS Three different agents were given after hair removal, and the samples were extracted by microdialysis and detected by HPLC. Subcutaneous/plasma concentration-time curves of the 3 different agents were analyzed and the pharmacokinetic parameters were calculated. The SS-04B UV light therapy instrument was used in the modeling. Changes in melanin index and histopathology were observed with HE staining. RESULTS The increment and decrement results showed that the concentration had no significant effect on drug recovery both in vivo and in vitro. After the paeonol cubic liquid crystalline nanoparticles gel (PAE-LCNPs) was administered, the maximum peak time (tmax) of paeonol skin concentration appeared at 2.42±0.20 h, the maximum skin concentration Cmax was (926±105) ng/ml, and the area under the curve AUC0-8 was (8056±954) ng/h/ml. The tmax was shortened much more than in the other groups, and the performance of PAE-LCNPs targeting was good. Pharmacodynamic results showed that PAE-LCNPs can reduce melanocytes and reduce the melanin index, proving its utility in the treatment of melanin deposition. CONCLUSIONS The skin microdialysis study indicated PAE-LCNPs have good transdermal permeability and efficacy. Pharmacological experiments based on the study found that the topical pigmentation model of guinea pigs showed a better therapeutic effect.

[Predictive analysis on Shenmai injection-induced adverse reactions with Logistic model and ROC curve].

To study relevant risk factors of Shenmai injection induced adverse reactions by using Logistic model and ROC curve, and made the prediction for the occurrence of relevant adverse reactions/events. Case data of patients treated with Shenmai injection were collected by using the prospective, multi-center, large-sample, nested-case control method, in order to analyze the risk factors of Shenmai injection-induced adverse reactions/events, establish the logistic model and draw the receiver operating characteristic (ROC) curve for risk factors. During the study, 7632 patients (including 3 477 males and 4 155 females) were included, and eight of them suffered adverse reactions/events. Based on a multi-factor Logistic model analysis, the age (> or = 50 years) (OR = 5.061, 95% CI: 2.197-7.924; P = 0.001), the total number of medication days (OR = -1.020, 95% CI: -l.652 - 0.388; P = 0.002) and the single dose (OR = 0.245, 95% CI: 0.127-0.364; P = 0.000) were significant independent risk factors for Shenmai injection-induced adverse reactions/events. According to the results, ROC curves were drawn with age (> or = 50 years), the total number of days of inedication and single dose; The area under ROC curves the joint predictor (0.9753, 95% CI: 0.9443-1.000, P < 0.005) was larger than that of the other three single indexes, with a higher risk prediction value. The independent risk factors for Shenmai injection-induced adverse reactions/events included the age (> or = 50 years), the total number of days of medication and single dose. In clinical practice, the age (> or = 50 years), the total number of days of medication and the medication dose can be substituted in the joint predictor calculation formula (P = 1 / [1 + e(-(-21.58 + 5.061 x Xage - 1.020 x Xd + 0.245 x X(mL)] to predict the potential adverse reactions of patients and adjust the dosage regimen.