Characterization of the metabolites of trans-resveratrol-3-O-glucoside in monkeys and dogs.

In this study, a liquid chromatography-tandem multi-stage mass spectrometry (LC/MSn) method was established to characterize the metabolites of TRG in monkeys and dogs. A total of seven metabolites of TRG besides the prototype were found, which were identified as TR (M1), TRN (M2), trans-resveratrol-4'-O-glucuronide (M2'), trans-resveratrol-3-O-glucoside-4'-O-glucuronide (M3), trans-resveratrol-3-O-glucoside-5-O-glucuronide (M3'), trans-resveratrol-3-sulfate (M4) and trans-resveratrol-4'-sulfate (M4'). Additionally, the metabolic pathways of TRG in monkeys and dogs were proposed. There were also species differences of metabolism of TRG between monkeys and dogs.

The effects of salvianolic acid B from radix salvia miltiorrhizae on the oral pharmacokinetics of metoprolol and metoprolol acid in rats.

The present study aimed to investigate the effects of salvianolic acid B (SalB) isolated from Radix Salvia miltiorrhizae on the oral pharmacokinetics of metoprolol (MET) and metoprolol acid (META) in rats. The pharmacokinetic parameters of MET and META were measured after oral (15 mg/kg) administration of MET in rats in the presence and absence of SalB. Compared to the control given MET alone, with the concurrent administration of SalB (50 mg/kg), the AUC and C(max) of MET increased by 51.7% and 27.7%, and the AUC and C(max) of META decreased by 26.5% and 19.6%, respectively. With the presence of SalB, the metabolic ratio was markedly decreased by 50.8%. However, no significant changes were observed in the pharmacokinetic parameters of SalB when it was combined with MET.

Pharmacokinetics of vertilmicin, a novel aminoglycoside antibiotic, in rats and dogs.

The pharmacokinetics of vertilmicin was investigated in rats and dogs following intramuscular or intravenous administration of vertilmicin. Following a single administration of an intramuscular dose, serum concentrations of vertilmicin peaked at 0.63 h in rats and 0.58 h in dogs. In rats, after intravenous administration of vertilmicin at dosages of 10, 20, and 40 mg/kg, the t1/2 values for vertilmicin were 0.81, 0.76, and 0.86 h, respectively, while after intramuscular administration of vertilmicin at dose of 20 mg/kg, the t1/2 value for vertiImicin was 0.79 h. In dogs, after intravenous or intramuscular administration of vertilmicin at a dose of 10 mg/kg, the t1/2 values for vertilmicin were 0.83 and 0.85 h, respectively. After intravenous dosing to rats vertilmicin was distributed to most organs and tissues, and kidney tissue exhibited the highest exposure, while the tissue with the lowest exposure was the brain. Following single intravenous administration of vertilmicin at a dose of 20 mg/kg to rats, about 81.1% of the vertilmicin was excreted in urine, while only 3.12 and 1.44% of the administered dose was excreted in feces and bile within 48 h. The mean values for the plasma protein binding of vertilmicin were 22.7 and 20.4% in rats and dogs, respectively. These results indicate that vertilmicin was rapidly absorbed and widely distributed into various tissues in rats. The pharmacokinetic behavior of vertilmicin was dose-dependent when increasing doses of vertilmicin were administered intravenously to rats. Renal excretion was the primary elimination route of vertilmicin following intravenous administration to rats.

[Metabolism of trans-resveratrol-3-O-glucoside in vitro in rat tissues].

To study the metabolism of trans-resveratrol-3-O-glucoside (TRG) in vitro in rat tissues, the incubation with cell-free extracts from rat stomach, duodenum, jejunum, ileum and liver was performed, separately. After TRG was incubated with the tissue extracts at 37 degrees C for up to 90 min, the deglycosylation of TRG was (3.50 +/- 0.24) % for stomach, (65.7 +/- 5.94)% for duodenum, (83.5 +/- 6.43)% for jejunum, (77.6 +/- 6.26)% for ileum and (9.62 +/- 1.21)% for liver, separately. It was observed that the small intestine extracts were more active in deglycosylation of TRG than the liver extract, which suggested that the small intestine mucosa played an important role in deglycosylation of TRG. It was assumed that the deglycosylation of TRG was catalyzed by beta-glucosidase in small intestine mucosa.

Pharmacokinetics of C-1027 in mice as determined by TCA-RA method.

AIM: To validate a radioactivity assay, the TCA-RA method, for the measurement of C-1027 in serum and to evaluate its application in determination of pharmacokinetics of C-1027 in mice. METHODS: (125)I-C-1027 was prepared by the Iodogen method and separated by HPLC. The radioactivity assay was established and used to determine (125)I-C-1027 in mice at doses of 10, 50 and 100 microg/kg after precipitation with 20% trichloroacetic acid (TCA-RA method). Several pharmacokinetic parameters were determined after intravenous injection of (125)I-C-1027 to mice. RESULTS: After intravenous injection of (125)I-C-1027 to mice, at doses of 10, 50 and 100 microg/kg; the apparent distribution volumes (V(d)) were 0.26, 0.31 and 0.33 L/kg; the biological half-lives (T(1/2)) were 3.10, 3.40 and 3.90 h; the areas under curve (AUC) were 18.41, 103.69 and 202.74 ng/h/mL; the elimination rate constants (K) were 1.04, 1.26 and 0.58/h; and the total body clearance (Cl) were 0.54, 0.48 and 0.49 L/kg/h, respectively. CONCLUSION: TCA-RA is a sensitive, reliable and suitable method for the determination of (125)I-C-1027 in mouse serum.

[Electrospray ion trap mass spectrometry of eight aminoglycoside antibiotics].

AIM: To study the dissociation pathways of aminoglycoside antibiotics. METHODS: In positive mode, eight aminoglycoside antibiotics were elucidated by use of electrospray ion trap mass spectrometry in the multi-stage MS full scan mode. RESULTS: It was demonstrated that the eight aminoglycoside antibiotics gave abundant product ions at m/z 322 (gentamicin, micronomicin and sisomicin), m/z 350 (etimicin, netilmicin and vetilmicin) and m/z 324 (kanamycin and tobramycin) by loss of the C-ring (amino-alpha-D-glucopyranose) in MS2 full scan mode. In MS3 full scan mode, the prominent fragmentation ions at m/z 163 as well as m/z 191 were formed from the fragmentation ions at m/z 322, m/z 350 and m/z 324 by loss of the A-ring (amino-alpha-D-glucopyranose), separately, while the characteristic fragmentation ions at m/z 160 as well as m/z 162 were formed from m/z 322, m/z 350 and m/z 324 by loss of the B-ring (2-deoxy-D-streptamine), separately. CONCLUSION: The structural information was obtained via collision-activated dissociation and these characteristics are applicable to the structural elucidation and quantitative analysis of aminoglycoside compounds.