ABSTRACT
OBJECTIVE: To study the pharmacokinetics of linezolid eye drops in rabbit eyes after a single dose administration. METHODS: Forty New Zealand rabbits are topically applied 50 μL of linezolid eye drops. Ocular tears, aqueous humour, cornea and conjunctiva are sampled at different intervals after drug instillation, and the drug levels are assayed by HPLC. The pharmacokinetic parameters are calculated by DAS 2.1.1 process. RESULTS: The peak concentrations of linezolid in tears, aqueous humour, cornea and conjunctiva are (2861.15±669.43) μg · g-1, (165.71±115.04) μg · mL-1, (58.62±15.48) μLg · g-1, and (305.02±287.64) μg · g-1, respectively. The half-lives of elimination are (60.67±25.59), (36.81±37.39), (38.09±11.59), and (19.85±7.06) h and AUC0-∞ are (4211.92±806.09) μg · h · g-1, (1634.65±1174.85) μg · h · mL-1, (2834.13±578.96) μg · h · g-1, and (3883.84±1846.13) μg · h · g-1, respectively. Blank tears, aqueous humour, cornea and conjunctiva didn't interfere with the determination of linezolid. CONCLUSION: Linezolid has a good pharmacokinetic character and permeability in rabbit eyes.
ABSTRACT
Background Ginkgolide B (GB) has been proved to have neuroprotective and anti-apoptotic effects and can effectively inhibit apoptosis of retinal photoreceptor cells.But the high hydrophobic feature and low bioavailability of GB limit its clinical application.Self microemulsifying drug delivery system (SMEDDS) can effectively improve the infusibility drug dissolution and bioavailability in the retina.Objective This study was to investigate the pharmacokinetics and drug-time change of GB-loaded SMEDDS in retina.Methods Eighty SD rats were randomized into 2 groups,2.5％ GB(40 mg/kg) of SMEDDS or GB suspension(0.1％ DMSO dissolve) were gastrically given respectively in two groups.The rats were sacrificed and retinas were isolated 15,30,45 minutes and 1 hour,2,4,8,12 hours to prepare the retinal suspension.The content of GB in retina was assayed with high performance liquid chromatography-electrospray ionization-(1) (1)ss spectrum (HPLC-ESI-MS) and contrasted with standard curve.Practical drug dynamics program 3p87 was used to detect the pharmacokinetics parameters.The maximal content(Cmax,mg/g),time to peak (Tmax,h),clearance ratio (Ke/h),high-life period (t1/2) and area under the concentration-time curve(AUC0-∞,mg/(g · h)) of GB in various time points in retina after a single oral dose were calculated and compared between two groups.Results The standard curve was obtained over the concentration range of 1-32 mg/L with a linear regression equation,Y =0.0732X + 0.056 (r =0.992).A similar content-time curve was seen between GB suspension group and GB-SMEDDS group.The GB content was higher in GB-SMEDDS group than that in GB suspension group from 30 minutes through 12 hours after administration of drugs.The Cmax of GB-SMEDDS group and GB suspension group were(15.83±1.84) mg/g and(2.65±0.10) mg/g,the AUC0-∞ were(15.30±0.11)mg/(g· h)and(6.42±0.19)mg/(g · h).Conclusions HPLC-ESI-MS is proved to be a rapid,accurate,sensitive and suitable method for pharmocokinetic study of GB.SMEDDS can raise the concent of GB in retina,and it probably improve the bioavailability of GB.
ABSTRACT
Apoptosis was induced by taxol treatment in suspension cultures of Taxus cuspidata cells. Differential display technique was used to investigate the induced-gene expression between the taxol-induced T. cuspidata cells and normal control. Eight different expressed cDNA fragments were cloned and sequenced. These differential expressed fragments were further confirmed by Northern blotting hybridization with their original total RNAs. The result showed that three of the cDNA fragments were from control RNA and five of those were from taxol-induced T. cuspidata cells. The homology of the sequences revealed that one of the clones had 86% homology with ABA-responsive protein gene sequence in Arabidopsis thaliana, two of the clones had 50% homology with endochitinase precursor in tomato and the other 5 clones, which might be new gene fragments, had no significant homology with the known gene sequences in GenBank/EMBL/DDBJ.