Objective To carry out a pharmacokinetic evaluation of oral FK506 in 13 patients after renal transplant. Methods 13 patients after renal transplantation were given prograf based immunosupressive regimen 24 hours after surgery.Blood samples to determine FK506 levels were drawn in heparinized tube at 0、20、40、60、90 min and 2、3、6、8、10 hours after the first oral dosing.The whole blood concentrations were measured by MEIA and the pharmacokinetic parameters were calculated by 3P87 program.The FK506 doses were recorded in detail for the first month. Results Cmax was (13.6259?4.1117)ng/ml;T(peak) was (1.4866?1.0725)h;t1/2 ? was (0.7749?0.7791)h,t1/2 ? was (10.7267?10.4926)h;AUC was (91.0415?40.7694)ng?ml -1 ?h -1 ,CL was (0.046?0.0036)ng?ml -1 ?h -1 and MRT was (8.1540?4.2937)h.AUC was negative correlateld with prograf dose in the first month posttransplant (r=-0.53, P =0.038). Conclusions The absorption of oral administration of FK506 was rapid in patients after renal transplantation,and can achieve Cmax in (1.5?1.1)h,the mean half life time being 10.7 h.The pharmacokinetic parameters can be the guideline for FK506 application.

OBJECTIVE:To study the pharmacokinetics of oral single dose adefovir dipivoxil(ADV) tablet in Chinese healthy volunteers.METHODS:The study was a randomized,open,three-way crossover study.Twelve healthy volunteers were randomly assigned to receive single oral dose of 5 mg(Group A),10mg(Group B) or 30 mg(Group C) ADV tablets in three weeks.The plasma concentrations of ADV were determined by LC/MS/MS method.The pharmacokinetic parameters were computed.RESULTS:The main pharmacokinetic parameters in Group A,B and C were as follows:Cmax were(11.4? 3.7),(25.4? 8.2) and(76.3? 23.0) ng? mL-1;tmax were(1.69? 1.41),(0.90? 0.56) and(0.94? 0.50) h;AUC0～ t were(102.7? 51.7),(235.0? 82.3) and(715.4? 267.6) ng? h.mL-1;AUC0～ ∞ were(168.7? 30.7),(266.2? 83.7) and(741.5? 273.9) ng? h? mL-1,respectively.CONCLUSION:ADV tablets had a rapid absorption in healthy volunteers and the Cmax and AUC of adefovir tablets were directly correlated to doses.It is safe for healthy volunteers to take ADV tablets at a dose of 5～30mg.

Objective To investigate the changes of brain function in moderate and high myopia patients using fractional amplitude of low frequency fluctuation (fALFF),and discuss the correlation between brain function changes and clinical data of patients with myopia.Methods Totally 21 moderate and high myopia patients (myopia group),and 21 healthy volunteers (normal control group) who were matched with myopia patients in age and gender,were selected to take rs-fMRI examination.The difference of fALFF of brain functional activity in patients with myopia and normal controls was compared,and the correlation between the changes of fALFF and clinical data of patients with myopia was analyzed,Results Compared with normal control group,the fALFF values of myopia group in the region of the left inferior frontal gyrus,putamen and right inferior frontal gyrus,putamen and insula were significantly lower (all P ＜ 0.05,AlphaSim corrected).However,in bilateral cingulate gyrus,bilateral anterior cingulate gyrus,left postcentral gyrus,left superior parietal lobule and region,fALFF values were increased (all P ＜ 0.05,AlphaSim corrected).Conclusion Patients with myopia are accompanied by abnormal neuronal activity in many brain areas,which may reflect the dysfunction of language understanding and attention control in myopic patients.

Objective To establish a method of LC-MS/MS for determining cordycepin(Cor)and 3′-deoxyinosine(3′-Deo)concentration in rat plasma,and to study their pharmacokinetics in rats.Methods Protein was precipitated with methanol using 2-chloadenosine(2-Chl)as an internal standard.The chromatography was performed on Kinetex C18(3 mm×100 mm,2.6 μm,Phenomenex,USA)with gradient elution in aqueous(5 mmol·L-1 ammonium acetate)-methanol solution as mobile phase.ESI ion source was used for mass spectrometry,and positive ion multiple reaction monitoring(MRM)was used for scanning detection.The pharmacokinetics of Cor and 3′-Deo after oral administration of Cor(10 mg·kg-1)were studied in rats.Results Cor at 0.5-100 ng·mL-1 and 3′-Deo at 1-200 ng·mL-1 had good linearity,and the lower limits of quantification were 0.5 and 1 ng·mL-1,respectively.After oral administration of Cor in rats,the plasma concentration of Cor was low,which was mainly converted into the metabolite 3′-Deo.The Cmax of Cor and 3′-Deo were(5.4±3.4)and(142.0±50.0)ng·mL-1,and AUC0-360min min were(658.4±459.3)and(18 034.9±4 981.1)ng·min·mL-1,respectively.Conclusion The method is simple,sensi-tive,and accurate,which is suitable for determining Cor and 3′-Deo concentration in plasma and the pharmacokinetic study.

Sympathetic cues via the adrenergic signaling critically regulate bone homeostasis and contribute to neurostress-induced bone loss, but the mechanisms and therapeutics remain incompletely elucidated. Here, we reveal an osteoclastogenesis-centered functionally important osteopenic pathogenesis under sympatho-adrenergic activation with characterized microRNA response and efficient therapeutics. We discovered that osteoclastic miR-21 was tightly regulated by sympatho-adrenergic cues downstream the β2-adrenergic receptor (β₂AR) signaling, critically modulated osteoclastogenesis in vivo by inhibiting programmed cell death 4 (Pdcd4), and mediated detrimental effects of both isoproterenol (ISO) and chronic variable stress (CVS) on bone. Intriguingly, without affecting osteoblastic bone formation, bone protection against ISO and CVS was sufficiently achieved by a (D-Asp₈)-lipid nanoparticle-mediated targeted inhibition of osteoclastic miR-21 or by clinically relevant drugs to suppress osteoclastogenesis. Collectively, these results unravel a previously underdetermined molecular and functional paradigm that osteoclastogenesis crucially contributes to sympatho-adrenergic regulation of bone and establish multiple targeted therapeutic strategies to counteract osteopenias under stresses.
Adrenergic Agents/pharmacology* ; Apoptosis Regulatory Proteins/pharmacology* ; Bone Diseases, Metabolic/metabolism* ; Humans ; Liposomes ; MicroRNAs/genetics* ; Nanoparticles ; Osteoclasts ; Osteogenesis/physiology* ; RNA-Binding Proteins/pharmacology*