[Study of fraction amplitude of low frequency fluctuation on resting-state functional magnetic resonance imaging in adultperipheral facial paralysis].

Objective: To analysis the change of brain functional activity in the left and right peripheral facial paralysis by using resting-state functional magnetic resonance imaging (R-fMRI) of fraction amplitude of low frequency fluctuation(fALFF) measurement technique, and research the abnormal brain region with different side patients whether there are differences. Methods: A total of 43 patients with peripheral facial paralysis patients (patient groups, divided into left / right two subgroups) and 21 healthy volunteers (control group) in this study.Resting-state fMRI were acquired for each volunteer and patient. The fALFF approach was used to compare the peripheral facial paralysis groups to healthy group.Functional analysis was performed with brain function analysis software REST and DPARSFA , and then analysis the difference of two groups of patients and control group in two sample t test.At the same time, the correlation analysis between fALFF parameters map of the left and right side of two groups of patients and corresponding facial nerve grading TFGS score.Ultimately obtain a statistically significant brain regions. Results: Compared to healthy group, the decreased fALFF areas in the left side facial paralysis were showed in the right superior temporal gyrus , the pole of the right temporal, right middle temporal gyrus, the left occipital gyrus, and left medial cingulate gyrus, left paracentral lobule, and the left supplementary motor area; while the increased brain regions have the right superior frontal gyrus, right middle frontal gyrus, the right precentral gyrus, bilateral inferior temporal gyrus and middle temporal gyrus.Compared to healthy group, the decreased fALFF areas in the right side facial paralysis were showed in the right inferior temporal gyrus and fusiform gyrus, the left inferior occipital gyrus, the left superior parietalgyrus, the left inferior parietalgyrus, left precuneus, left paracentral lobule, the left supplementary motor area; while the increased brain regions have the left Calcarine, right lingual gyrus, corpus callosum, right medial cingulum gyrus.In the left facial paralysis group TFGS score was positively correlated with brain regions have left middle frontal gyrus, left precuneus and left cuneus, while the negatively related brain area on the right lingual gyrus.In the right facial paralysis groups TFGS score was positively correlated with brain areas have right inferior temporal gyrus and middle temporal gyrus, left inferior parietalgyrus; while the negatively correlated brain area on the left superior temporal gyrus, the right medial frontal gyrus. Conclusion: The left and right side facial paralysis patient's mood and motor function integration mechanism may be different, and the patient's emotional and psychological changes may be associated with disease severity.

Pharmacokinetic study of icariside II after a single dose administration of YiGu capsule in healthy Chinese volunteers.

To investigate the pharmacokinetic characteristics of icariside II after a single oral dose administration of YiGu Capsule in healthy -Chinese volunteers. 8 (4 female) healthy Chinese volunteers were involved and administrated for 15 doses of YiGu Capsule after fasting overnight. 4 ml of blood samples were collected at scheduled time before and after administration. Icariside II in human plasma was separated on a Agela Venusil XBP-C18 column (250 mm×4.6 mm, 5 µm), and eluted using acetonitrile-water (containing 0.1% formic acid) (70:30, V/V) as mobile phase. The analytes were detected with a -triple quad HPLC-MS/MS using ESI with positive ionization. Ions monitored in the multiple reaction monitoring mode were m/z 515.1 (precursor ion) to m/z 369.1 (product ion) for icariside II and m/z 321.0 (precursor ion) to m/z 275.0 (product ion) for lorazepam (internal standard).The plasma concentration of icariside II was determined by established HPLC-MS/MS method after disposition and its pharmacokinetic parameters were analyzed and evaluated by PK Solver Software (version 1.0). The Cmax, Tmax, t1/2, AUC0-24, AUC0-∞, MRT0-∞-1, 2.50±1.91 h, 7.61±2.81 h, 12.68±4.86 ng · mL-1 · h, 14.22±5.75 ng · mL-1 · h, 9.55±1.56 h, 12.81±7.94 L · h-1 and 121.70±32.70 L. The established HPLC-MS/MS method was sensitive, selective and rapid for icariside II pharmacokinetic study.

Bioequivalence of two misoprostol tablets in healthy Chinese female volunteers: a single-dose, two-period, double crossover study.

OBJECTIVE: To assess the bioequivalence of a new generic formulation of misoprostol (CAS 59122-46-2) 0.2 mg tablets (test) and the available branded tablet (reference) for the requirement of state regulatory criteria and the marketing of the test product in China. METHODS: A randomized-sequence, 2-period crossover study was conducted in 20 healthy Chinese female volunteers in the fasted state. Blood samples were collected at baseline and 0.083, 0.17, 0.25, 0.33, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4 and 6 h after a single oral dose of 0.6 mg misoprostol test or reference, followed by a 7-day washout period. Misoprostol acid, the active metabolite of misoprostol, was determined by an HPLC-MS/MS method. Drug And Statistics 2.0 was used to calculate the pharmacokinetics parameters and assess bioequivalence of the 2 formulations. It was considered bioequivalent if the 90% CIs of the mean ratios (test: reference) for Tmax, Cmax and AUC0-t were all within the range from 80% to 125%. Adverse events were monitored throughout the study based on clinical parameters and patient reports. RESULTS: The main pharmacokinetics parameters for the test and reference were as follows: t1/2 was (0.680 ± 0.371) h and (0.650 ± 0.264) h; Tmax was (0.415 ± 0.087) h and (0.399 ± 0.097) h; Cmax was (1.941 ± 0.417) ng/mL and (2.047 ± 0.397) ng/mL; AUC0-t was (1.535 ± 0.419) ng·h/mL and (1.652 ± 0.400)ng·h/mL, and the AUC0-∞ was (1.576 ± 0.465) ng·h/mL and (1.686 ± 0.396) ng·h/mL. The mean ratios (test: reference) for Cmax, AUC0-t, and AUC0-∞ were 95.3% ±13.2%, 92.65% ± 17.31%, and 93.61%±18.97%, respectively. No significant (p>0.05) differences in pharmacokinetic parameters were found between preparations, treatments and periods. CONCLUSIONS: This single-dose study in healthy Chinese fasted volunteers was shown that the misoprostol test and reference met the requirement of US and China regulatory criterion, and the test and reference were bioequivalent.

Determination of glycyrrhetic acid in human plasma by HPLC-MS method and investigation of its pharmacokinetics.

OBJECTIVE: To develop a high performance liquid chromatography mass spectrometry (HPLC-MS) method for the determination of the glycyrrhetic acid (GA) in human plasma and for the investigation of its pharmacokinetics after the oral administration of 150 mg diammonium glycyrrhizinate test and reference capsule formulations. METHODS: The GA in plasma was extracted with ethyl acetate, separated on a C(18) column with a mobile phase of methanol (5 mmol/L ammonium acetate)-water (85 : 15, V/V) and analysed using a MS detector. Ursolic acid (UA) was used as internal standard. The target ions were m/z 469.5 for GA and m/z 455.6 for UA, the fragment voltages were 200 V and 100 V for GA and UA respectively. RESULTS: The calibration curve was linear over the range of 0.5-200 ng/mL (r = 0.9974). The limit of quantification for GA in plasma was 0.5 ng/mL, the recovery was 76.0-80.0%, and the inter- and intra-day relative standard deviations (RSD) were <12%. The pharmacokinetic parameters of GA after a single dose of 150 mg diammonium glycyrrhizinate test and reference were as follows: the half life (t(1/2)) 9.65 +/- 3.54 h and 9.46 +/- 2.85 h, the time to peak concentration (T(max)) 10.95 +/- 1.32 h and 11.00 +/- 1.30 h, the peak concentration (C(max)) 95.57 +/- 43.06 ng/mL and 103.89 +/- 49.24 ng/mL; the area under time-concentration curve (AUC(0-48) and AUC(0-infinity)) 1281.84 +/- 527.11 ng.h/mL and 1367.74 +/- 563.27 ng.h/mL, 1314.32 +/- 566.40 ng.h/mL and 1396.97 +/- 630.06 ng.h/mL. The relative bioavailability of diammonium glycyrrhizinate capsule was 98.88 +/- 12.98%. CONCLUSION: The assay was sensitive, accurate and convenient, and can be used for the determination of GA in human plasma. Comparison of the bioavailability and pharmacokinetic profile of GA indicated that the test and reference capsules were bioequivalent.