Comparative Pharmacokinetic Study of Mangiferin in Normal and Alloxan-Induced Diabetic Rats after Oral and Intravenous Administration by UPLC-MS/MS.

BACKGROUNDS: Diabetes mellitus (DM)-induced morphological and/or functional complications may alter the pharmacokinetic profiles of mangiferin. This study aims to compare pharmacokinetic profiles of mangiferin in normal and alloxan-induced diabetic rats after oral and intravenous administration. METHODS: Mangiferin was administered orally (10 mg/kg) and intravenously (2 mg/kg) to normal and alloxan-induced diabetic Sprague-Dawley (SD) rats (n = 8). Blood samples were collected at different time points post-dose. Mangiferin and esculentoside (internal standard)  were analyzed by Waters Acquity ultra-performance liquid chromatography system and TSQ Quantum Ultra triple quadrupole mass spectrometer (UPLC-MS/MS). RESULTS: Mangiferin in normal and alloxan-induced diabetic rats experienced serious first-pass effect, which resulted in 1.71 and 0.80% of oral bioavailability respectively. Meanwhile, mangiferin was predominantly restricted to blood but not extensively distributed to organ tissues after intravenous administration. Compared with normal rats, the diabetic condition induced 53.26 and 50.90% decreases in Cmax and AUC0-t, respectively, for mangiferin after oral administration, and 63.08% decreases in Cmax after intravenous administration. CONCLUSIONS: Compared to normal rats, pharmacokinetic parameters of mangiferin were altered in diabetic condition induced by alloxan. The findings might help to provide useful evidence for modeling of diabetic rats and the clinical applications of mangiferin.

Pharmacokinetics of single- and multiple-dose emtricitabine in healthy male Chinese volunteers.

Emtricitabine (FTC) is used for the treatment of HIV infection and pre-exposure chemoprophylaxis. It is often used in combination with tenofovir disoproxil fumarate (TDF). This study was designed to evaluate FTC pharmacokinetics in healthy male Chinese volunteers. Sixty subjects were recruited into this single-centre, randomised, open-label study and randomly received single (groups A, B and C) or multiple oral doses (once daily for 6 days; groups D, E and F) of 200-mg FTC capsules alone (A and D), or combined with 300-mg TDF tablets (B and E), or 200 mg of FTC plus 300 mg of TDF with a high-fat diet (C and F), respectively. FTC was well-tolerated in all groups. After a single dose, there were no differences in the mean AUC0-∞ values; however, there were significant differences in the mean Tmax values (1.05, 1.40 and 2.10 h for groups A, B and C, respectively; p < 0.05). In the multiple-dose study, our results were significantly different from published t1/2 values following single-dose FTC.

[Pharmacokinetics of hylotelephin in Beagle dogs].

AIM: To investigate the pharmacokinetics of hylotelephin in Beagle dogs and obtain the main pharmacokinetic parameters. METHODS: An HPLC method with UV detection was developed to study the pharmacokinetics of hylotelephin in dogs by joining an internal standard (anthracene). Benzoyl chloride was used to the pre-column derivatization of hylotelephin and methanol-water (64:36) was used as the mobile phase. According to the 3P97 pharmacokinetic program, the main parameters were calculated. RESULTS: The hylotelephin pharmacokinetics conforms to a two-compartment open model after a single iv dose of hylotelephin 10.6 or 21.3 mg x kg(-1) in Beagle dogs. The parameters of two groups were as follows: T(1/2) alpha were 2.3 and 2.1 min, T(1/2) beta were 1.9 and 2.0 h, K12 were 0. 12 and 0.11 min, K21 were 0.17 and 0.21 min, K10 were 0.011 and 0.0094 min, Vc were 0.54 and 0.54 L x kg(-1), AUC were 1.8 and 4.1 g x min x L(-1), CL were 0.0048 and 0.0056 L x kg(-1) x min(-1), MRT were 2.10 and 2.4 h, respectively. CONCLUSION: The pharmacokinetics of hylotelephin after iv administration showed a rapid distribution and elimination process in Beagle dogs and was of first order kinetics.

[Protective effects of total alkaloids from rhizoma Coptis chinensis on alcohol-induced gastric lesion in rats].

OBJECTIVE: To study the effects of total alkaloids(TA) from rhizoma Coptis chinensis on alcohol-induced gastric lesion in rats and the possible mechanisms. METHOD: The experimental gastric damges were established by intragastric(ig) absolute ethanol, and possible protective effects of TA given orally previously were evaluated by following parameters: gastric damage indexes, gastric juice volume, acidity, and mucus quantity. The contents of NO, MDA, *OH, and SOD activity were also measured in gastric mucosa. RESULT: TA showed significantly inhibitive effects on gastric damages induced by ig ethanol in a dose dependent manner. The effects of TA (120 mg x kg(-1)) were stronger than that of both cimitidine(70 mg x kg(-1)) and berberine(100 mg x kg(-1)), the quantity of later was equal to TA as calculated with berberine. TA significantly suppressed secretion of gastric acid caused by ethanol without clear influences on gastric juice volume and mucus secretion. TA obviously blunted ethanol-induced elevation of MDA and *OH, as well as decrease of NO level and SOD activity from gastric mucosa. CONCLUSION: It is suggested that the TA is a potent protective agent against ethanol-induced gastric damages. The mechanism of actions may be related with inhibiting the secretion of gastric acid and blunting the increase of MDA and *OH, as well as the decrease of NO level and SOD activity from gastric mucus.

Simultaneous determination of eleven compounds related to metabolism of bioamines in rat cortex and hippocampus by HPLC-ECD with boron-doped diamond working electrode.

A simple and rapid high-performance liquid chromatography method with electrochemical detection employing boron-doped diamond electrode (BDD) was established for simultaneous determination of eleven bioamines with their precursor amino acids and metabolites, including two precursors (tyrosine and tryptophan), three catecholamines (dopamine, norepinephrine and epinephrine) and their four metabolites (3,4-dihydroxyphenylacetic acid, 3-methoxytyramine, homovanillic acid, and 3-methoxy-4-hydroxyphenylglycol), as well as serotonin and its metabolite (5-hydroxyindoleacetic acid), in a single run of 20 min using vanillic acid as internal standard. The separation was performed on an ODS2 column (250 mm × 4.6 mm, 5.0 µm) with column oven temperature of 30 °C. Quantification was accomplished at an oxidation potential of 700 mV vs Ag/AgCl reference electrode after a range of applied voltages were tested. Several parameters of this new chromatographic method were validated after optimizaton of the analytical conditions. The new method was successfully applied to test cortex and hippocampus samples from Sprague-Dawley rats with good separation. These eleven compounds in cortices and hippocampi were compared, which was used for monitoring their variations in neuroscience research.

[Study of total alkaloids from Rhizoma Coptis Chinensis on experimental gastric ulcers].

OBJECTIVE: To study the effects of total alkaloids (TA) extracted from Rhizoma Coptis Chinensis on experimental gastric ulcer models. METHODS: Four kinds of experimental ulcer models were established respectively by water-immersion stress, intragastric ethanol, acetic acid erosion, and pylorus ligation. The anti-ulcer effects of TA were evaluated, and compared with that of berberine (Ber) and cimetidine (Cim). RESULTS: TA showed significant inhibitory effects on ulcerative formation induced by water-immersion stress, intragastric ethanol, and pylorus ligation in dose-dependent manner, and showed therapeutic effect on acetic acid erosion-inducing ulcer, in comparison with the control group. The anti-ulcer activity of Ber was less than TA containing equal content of Ber. TA significantly reduced the free acidity, total acidity and total acid output, but didn't affect the gastric juice volume, gastric pepsin activity, adherent mucus quantity of stomach wall and free mucus dissolving in gastric juice. The suppressive activities of TA on gastric acid secretion didn't occur when it was administered into dodecadactylon at a dose of 360 mg/kg wt. Moreover, when compared with Cim, the inhibitory effect of TA on gastric acid secretion isn't proportional to the inhibitory effects on the formation of the 4 kinds of experimental ulcers. CONCLUSION: TA is a potent candidate in therapeutic drugs for treating gastric ulcer. Its anti-ulcer effective components and mechanism is not only related to Ber and inhibition of gastric acid, but also to other ingredients of TA and mechanism so far unknown.