Dose-dependent pharmacokinetics of glycyrrhizin in rats.

The dose-dependent pharmacokinetics of glycyrrhizin (GLZ) was investigated by measuring drug disappearance from plasma and biliary excretion in rats. The decline in plasma concentration was biexponential after an i.v. dose of 5, 10, 20, or 50 mg/kg. Dosage, however, had a marked effect on the pharmacokinetics, with a greater-than-proportional increase in area under the plasma concentration curve (AUC) at doses of 20 and 50 mg/kg, even though the increase was proportional at doses of 5 and 10 mg/kg. There was also a significant increase of the steady-state distribution volume (Vdss), as well as significant decreases in total body (CLtot) and biliary (CLB) clearances, at 20 and 50 mg/kg from those at 5-10 and 5-20 mg/kg, respectively. The AUC, Vdss, and renal clearance (CLR) at a given dose showed no significant difference between rats with and without bile fistulas. The plasma unbound fraction (fp) (0.006-0.026) increased with increasing plasma GLZ concentration over the observed range (2-900 micrograms/ml). No significant change in Vdss for unbound GLZ was observed between the doses, indicating that the distribution of GLZ into tissues is not changed by an increase in dose. On the other hand, a dose dependency in CLtot for unbound GLZ was observed and confirmed to be attributed to dose dependency in CLB for unbound GLZ since there was no significant difference in CLR or metabolic clearance for unbound GLZ between the doses.(ABSTRACT TRUNCATED AT 250 WORDS)     

Determination of tolperisone enantiomers in plasma and their disposition in rats.

A stereoselective assay for the determination of tolperisone enantiomers in plasma by high performance liquid chromatography was developed. Calibration curves obtained for the enantiomers were linear over plasma concentrations of 0.1-3.0 micrograms/ml with a detection limit of 20 ng/ml. Following intravenous bolus administration of 10 mg/kg of racemic tolperisone to rats, stereoselective disposition of tolperisone enantiomers was observed, and plasma concentrations were significantly higher for l-tolperisone than for d-tolperisone at 5, 15 and 30 min after administration. When either enantiomer was administered alone to rats, both enantiomers were found in plasma, indicating that a mutual chiral inversion occurs in the body.     

Pharmacokinetics of brain natriuretic peptide in rats.

The pharmacokinetics of rat brain natriuretic peptide (rBNP) was compared with that of alpha-rat atrial natriuretic peptide (alpha-rANP) in rats. After intravenous infusion in rats (600 pmol min-1kg-1 for 2 min), the disappearance of plasma rBNP was 4-fold slower than that of alpha-rANP. The estimated mean plasma clearance rates for rBNP and alpha-rANP were 45.9 ml min-1kg-1 and 74.4 ml min-1kg-1, respectively. The affinity of rBNP for the clearance receptor or degradation enzyme was considered to be lower than that of alpha-rANP.     

Mechanisms of pharmacokinetic interaction between propranolol and quinidine in rats.

In order to study the mechanism of propranolol-quinidine interaction, the effects of quinidine on propranolol pharmacokinetics were examined in male Wistar rats. The concurrent oral administration of quinidine (10 mg/kg) markedly increased the plasma concentration of propranolol (2.5 mg/kg), and the area under the propranolol concentration-time curve increased about 3.6-fold. These results are consistent with previous observations in man and indicate the possible usefulness of the male Wistar rat as an animal model for investigating the mechanisms of the drug interaction. When propranolol was given intravenously, a concurrent administration of quinidine increased the apparent distribution volume of propranolol, mainly by decreasing its plasma protein binding. However, the systemic clearance of propranolol was not significantly altered by quinidine. Thus, quinidine increased the availability of oral propranolol from 13.8 +/- 2.2 to 44.2 +/- 4.6% (p less than 0.01). Furthermore, quinidine delayed the elimination of propranolol from the isolated perfused rat liver. These results indicate that quinidine reduces the presystemic elimination of propranolol in the liver, thereby increasing its systemic availability after oral administration.     

Antihyperglycemic activity of Rhizophora apiculata Bl. in rats

The article reveals the antihyperglycemic activity of the ethanolic extract of the roots of the Rhizophora apiculata in rats (GLM and STZ models). On further fractionation of the ethanolic extract into four fractions, the activity was localized in the chloroform and aqueous fractions. These on purification led to the isolation of 7 pure compounds--lupeol (1), oleanolic acid (2), beta-sitosterol (3), palmitic acid (4), beta-sitosterol-beta-D-glucoside (5), inositol (6), and pinitol (7). The inositol and pinitol, two of the pure compounds, showed promising activity in STZ model at 100 mg kg(-1) dose level.     

Pharmacological properties of galenical preparation. XV. Pharmacokinetics study of evocarpine and its metabolite in rats.

It is known that when methanol extract of Evodia fruit is orally administered, 5-(1,4-dihydro-1-methyl-4-oxo-2-quinolin-2-yl) pentanoic acid (EVCA) is excreated as a matabolite in rat urine. In this study, we separated Evodia fruit extract into major alkaloids administered each alkaloid individually to male Wistar rats. Consequently, it was demonstrated that the original substance of the metabolite are evocarpine and its analogues, dihydroevocarpine and 1-methyl-2-undecenyl-4(1H)-quinolone. Investigation of a blood sample after oral administration of evocarpine by high performance liquid chromatography confirmed that the substance was absorbed without alteration. Pharmacokinetics of evocarpine after intravenous injection was expressed in a one-compartment model, showing a linear elimination of plasma evocarpine up to a dosage of 75 mg/kg. Total plasma clearance (CL), volume of distribution (Vd), and half-life (T1/2) of evocarpine were 60 ml/min.kg, 3.21/kg and 0.6 h-1, respectively. Metabolic ratio of evocarpine into EVCA after intravenous injection was 15.4%, and absorption ratio of the unaltered compound calculated from the levels of AUC after oral administration and intravenous injection was 4.7%. In this paper, it is shown that evocarpine is absorbed amount 100% when it is administered orally.     

Ascertainment of D-amino acids in germ-free, gnotobiotic and normal laboratory rats.

Free D-amino acids were ascertained in the blood serum, urine and aqueous ethanolic extracts of feces of germ-free laboratory rats and a rat made gnotobiotic (tetra-associated) with species of Streptococcus, Lactobacillus and Clostridium. D-Amino acids were also determined in the brains of two germ-free rats. For comparison, D-amino acids were also measured in the blood serum of normal rats and the blood plasma, urine and feces of normal white mice. D-Enantiomers of most protein L-amino acids were detected in all physiological samples of animals. Quantities of free D-amino acids were determined as N(O)-pentafluoropropionyl-(2)-propyl esters by enantioselective gas chromatography and mass spectrometry. Stereoisomers of the bacterial marker 2,6-diaminopimelic acid, analyzed as N-trifluoroacetyl-(2)-propyl esters, were detected in feces of the gnotobiotic but not of the germ-free rat.     

Antifertility activity of Piper longum Linn. in female rats

The crude extract, its different fractions and the major pure compound from the active fraction of the powdered fruits of Piper longum were studied for the antifertility effect in female rats. The crude extract and its hexane fraction exhibited 100 and 86% efficacy respectively (days 1-7 post-coitum (p.c.) schedule). On the other hand, 1-butanol soluble, 1-butanol insoluble and chloroform fractions were inactive.