ABSTRACT
Pharmacokinetics of 20 mg isosorbide-5-mononitrate (IS-5-MN) after single and multiple administration of two different tablet formulations were investigated in twelve healthy human subjects using an open, randomized, two-way crossover experimental design. Pentacard 20 mg tablets were compared with Ismo 20 mg tablets. After single-dose administration, both preparations caused a rapid increase in IS-5-MN plasma levels with the peak plasma concentration occurring between 0.5 and 1.5 h. For both formulations, the mean plasma half-life was found to be approximately 5 h after a single dose. In steady state during multiple dosing (t.i.d. at 8 h dosing intervals), a reduced elimination rate was observed. In line with this observation, the area under the plasma concentration-time curve (AUC) for one 8 h dosing interval during multiple dosing was higher than the extrapolated AUC after a single dose. Based on statistical evaluation of the various relevant pharmacokinetic parameters calculated from the plasma concentrations occurring after single and multiple dosing, the tablet formulations are judged to be bioequivalent.
Subject(s)
Isosorbide Dinitrate/analogs & derivatives , Administration, Oral , Adult , Biological Availability , Chemistry, Pharmaceutical , Drug Administration Schedule , Humans , Isosorbide Dinitrate/adverse effects , Isosorbide Dinitrate/pharmacokinetics , Male , TabletsABSTRACT
A universal rapid, sensitive and selective high-performance liquid chromatographic method with UV detection at 230 nm has been developed for the determination of benzamide drugs in human plasma and urine. Sample pretreatment is carried out using solid-phase extraction columns, resulting in very high extraction recoveries of the compounds investigated (alizapride, metoclopramide, alpiropride, amisulpride). The detector response is linear from 25 to 10,000 ng/ml, and the detection limit is 3 ng/ml for alizapride and 10 ng/ml for metoclopramide. The proposed method is highly suitable for pharmacokinetic studies and for drug monitoring.
Subject(s)
Anti-Arrhythmia Agents/analysis , Metoclopramide/analysis , Pyrrolidines/analysis , Anti-Arrhythmia Agents/blood , Anti-Arrhythmia Agents/urine , Chromatography, High Pressure Liquid , Humans , Indicators and Reagents , Metoclopramide/blood , Metoclopramide/urine , Pyrrolidines/blood , Pyrrolidines/urineABSTRACT
The effects of temperature, albumin, pH and Ca2+ on the binding of phenobarbitone and phenytoin to human serum albumin in buffer have been investigated using equilibrium dialysis. The free fractions of both anticonvulsants were much increased by raising the temperature. Lower free fractions were observed by increasing the albumin concentration from 5-8 g litre-1 and by raising pH from 6 to 9. No significant effect on the free fractions was observed by changing (at pH 7.4) the Ca2+ concentration from 0 to 5 mM. The observed differences in free fractions at 37 degrees C, as determined in phosphate, borate and Krebs-Ringer buffer at pH 7.4, indicate that great care is needed in the choice of dialysis fluid for dialysis of clinical samples.
Subject(s)
Phenobarbital/blood , Phenytoin/blood , Calcium/blood , Dialysis , Humans , Hydrogen-Ion Concentration , Serum Albumin/metabolism , TemperatureABSTRACT
In this study, three techniques for measuring the free fractions of phenobarbital and phenytoin were compared: equilibrium dialysis, ultrafiltration, and the Hummel and Dreyer method for gel permeation chromatography. In their therapeutic range (15-40 and 10-20 mg/L, respectively) the free fractions of phenobarbital and phenytoin were independent of the drug concentrations. Free fractions of phenobarbital as determined by equilibrium dialysis, ultrafiltration, and gel permeation chromatography were 58.7 +/- 1.8, 58.3 +/- 1.5, and 55.1 +/- 1.7%, respectively. Free fractions of phenytoin were 18.1 +/- 1.1, 17.0 +/- 2.1, and 19.4 +/- 1.2%, respectively. On lowering the albumin concentration, a similar increase in the free fractions of both drugs was observed with all three techniques. The results of this study show that all three techniques are suitable for the determination of free fractions of phenobarbital and phenytoin. Moreover, these techniques seem to be suitable for the investigation of physiological factors that may influence albumin drug binding.
