Simple method for determination of hydrochlorothiazide in human urine by high performance liquid chromatography utilizing narrowbore chromatography.

A simple high performance liquid chromatographic (HPLC) method utilizing narrowbore chromatography was developed for the determination of hydrochlorothiazide in human urine. A mobile phase of 0.1% aqueous acetic acid--acetonitrile (93:7, v/v) pH 3 was used with a C18 analytical column and ultraviolet detection (UV). The method demonstrated linearity from 2 to 50 micrograms ml-1 using 50 microliters of urine with a detection limit of 1 microgram ml-1. The method was utilized in a study evaluating if racial differences are present in the pharmacokinetic and pharmacodynamic effects of hydrochlorothiazide.

Hormonal, blood pressure, and peritoneal transport response to short-term ACE inhibition.

OBJECTIVES: To evaluate the hormonal, blood pressure, and peritoneal transport effects of intraperitoneal enalaprilat and oral enalapril. DESIGN: A nonrandomized, nonblinded, prospective clinical trial was performed. SETTING: The study was conducted at the Clinical Research Unit at the Medical College of Virginia, a tertiary care center. PATIENTS: Six continuous ambulatory peritoneal dialysis (CAPD) patients with hypertension were enrolled in the study. All 6 patients received intraperitoneal enalaprilat. Five of the patients also received oral enalapril. INTERVENTIONS: Hormonal, clinical, and transport parameters were investigated in patients given intraperitoneal enalaprilat and oral enalapril. Standardized 2-L exchanges were performed during a control period, following 2.5 mg intraperitoneal enalaprilat and after a week of oral enalapril. Inulin, blood urea nitrogen (BUN) and creatinine clearances, and glucose absorption were determined during these exchanges. RESULTS: After intraperitoneal enalaprilat, both systolic and diastolic blood pressure significantly declined, reaching maximal decreases of -21.7 +/- 14.2% at 95 +/- 92 minutes, and of -23.3 +/- 15.4% at 105 +/- 105 minutes, respectively. Plasma angiotensin converting enzyme (ACE) activity was suppressed below detectable limits at four hours following intraperitoneal enalaprilat, and remained suppressed throughout all sampling time points following oral enalapril treatment. There was no significant change in drain volumes, glucose absorption, or BUN, creatinine, or inulin clearances, whether enalaprilat was administered intraperitoneally or enalapril orally. CONCLUSION: This study demonstrates that intraperitoneal administration of enalaprilat is a rapidly effective route of administration of this ACE inhibitor. There were no changes in peritoneal transport characteristics demonstrated.

The effect of nonsteroidal agents (NSAIDs) on the pharmacokinetics and pharmacodynamics of metolazone.

NSAIDs attenuate the natriuretic response to loop diuretics. Their effect on the action of distal tubular diuretics is poorly explored. Accordingly, the pharmacokinetics and pharmacodynamics of metolazone [M], a distal tubular diuretic, with and without indomethacin [M+I] or sulindac [M+S] were examined in six healthy volunteers. Urine samples were obtained over 36 hours post-metolazone dosing for the determination of sodium, potassium and metolazone concentration. Though cumulative M excretion 750 +/- 247 [mucg/36 h] [M]; 749 +/- 239 [M+I]; 848 +/- 443 [M+S] was comparable between treatment groups, total sodium [Na+] excretion was significantly depressed in the presence of S or I, 685 +/- 114 [mEq/36 h] [M]; 454 +/- 90 [M+I] (p < or = 0.05); 553 +/- 123 [M+S] (p < or = 0.05). Peak Na+ excretion [muEq/min] was significantly decreased by I only and time to peak Na+ excretion did not differ amongst treatment groups. Total potassium [K+] excretion 160 +/- 39 [mEq/36 h] [M]; 111 +/- 53 [M+I] (p < or = 0.05); 135 +/- 31 [M+S] significantly decreased with I. This phenomenon was most evident between 12 and 36 hours. The administration of I or S with M significantly blunted sodium excretion on a purely pharmacodynamic basis while the decline in urinary potassium excretion upon addition of I to M related probably to an attenuation of braking phenomenon induced kaliuresis. These findings likely reflect NSAID-induced sodium reabsorption at loci prior to the site of action of metolazone.