Chronopharmacology of trichlormethiazide in rats: (III). Influence on serum triglyceride and glucose.

Trichlormethiazide was given orally to rats at 10 a.m. or 10 p.m. for 14 days. The diuretic effects of the agent at 10 a.m. were greater than those at 10 p.m. on day 14. Serum concentrations of triglyceride and glucose increased in both trials. The increments in these parameters were enhanced following trichlormethiazide at 10 a.m. These data indicate that the diuretic effects of trichlormethiazide and its untoward influences on serum metabolic parameters might vary with the administration time during a repeated therapy.

Chronopharmacology of trichlormethiazide in rats.

Trichlormethiazide was given orally at 1200 hrs or 2400 hrs to rats. Its diuretic effects were greater at 1200 hrs than at 2400 hrs. There were significant correlations between urinary trichlormethiazide and its effects in both trials. The regression lines of two trials did differ. These findings indicate that the effects of trichlormethiazide vary with its administration time. Time-dependent variations in urinary trichlormethiazide and susceptibility to the agent might be involved in this phenomenon.

Chronopharmacology of trichlormethiazide in rats; (II). Examination in aged rats.

We have previously demonstrated a time-dependent variability in the diuretic effects of trichlormethiazide, a thiazide diuretic agent, in young rats. The study suggested that the time-dependent variations in urinary trichlormethiazide and susceptibility of renal tissues to the agent might be involved in this phenomenon. The present study was undertaken to test a hypothesis that such a daily variation in the effects of trichlormethiazide is blunted by age. Trichlormethiazide (0.5 and 2.0 mg/kg) was given orally at 1200 hrs (day trial) or at 2400 hrs (night trial) in young (10-11 week old) and aged (23-24 month old) Wistar rats. Urine was collected for 8 hours after the agent and urinary excretions of sodium, chloride and trichlormethiazide were determined. Urine volume and urinary excretions of sodium, chloride and trichlormethiazide following the agent were significantly greater at 1200 hrs than at 2400 hrs in the young rats. However these administration time-dependent changes in the effects of trichlormethiazide and its urinary amount diminished in the aged rats. In the day and night trials, there were significant correlations between urinary trichlormethiazide and its effects (urine volume, urinary sodium and chloride) in both groups of rats. The regression lines in each parameter of two trials differed in the young, but not in the aged group of rats. These data indicate that the mode of the time-dependent changes in the effects of trichlormethiazide is altered in aged Wistar rats. Dampening of the time-dependent variations in urinary trichlormethiazide and susceptibility to the agent might be involved in these chronopharmacological alterations in aged rats.

On-line direct liquid introduction interface for micro-liquid chromatography/mass spectrometry: application to drug analysis.

We describe an integrated micro-liquid chromatograph/mass spectrometer (micro-LC/MS) system capable of performing routine determinations for 1--10 ng of drugs and their metabolites extracted from biological fluids. The micro-LC is constructed from conventional "high-performance" liquid-chromatographic instrumentation by using commercially available components. The mass spectrometer is operated in the chemical ionization mode. The direct liquid introduction micro-LC/MS interface can be constructed from commercially available materials. Chromatographic and mass spectral results demonstrate the ability of the micro-LC and micro-LC/MS system to separate and determine multiple components in standards of trace concentrations and in equine urinary extracts. The stability and sensitivity of this micro-LC/MS system are demonstrated through determinations of trichlormethiazide.