Rapid, simple and sensitive high-performance liquid chromatographic method for detection and determination of acyclovir in human plasma and its use in bioavailability studies.

A rapid, simple and sensitive reversed-phase high-performance liquid chromatographic (HPLC) method has been developed for the measurement of acyclovir concentrations in human plasma and its use in bioavailability studies is evaluated. Unchanged acyclovir has been quantified without the introduction of an internal standard using the present method. Human plasma proteins were selectively precipitated by the addition of 7% perchloric acid to spiked plasma samples or to the plasma samples obtained after acyclovir administration to human volunteers and the mixture was spun at 1000 g for 10 min. The supernatant was directly injected into a Novaflex C18 column and detected at 254 nm. The mobile phase consisted of octane sulfonic acid buffer (pH 2.5) and methanol (92:08). The limit of quantitation for acyclovir in plasma was 20 ng/ml, which enabled the determination of the area under the curve (AUC) more precisely, that is, it is much closer to its extrapolated value. The present method has been successfully applied to samples from bioavailability studies.

Effect of long-term treatment with enalapril in streptozotocin diabetic and DOCA hypertensive rats.

We studied the effects of long-term treatment with enalapril (5 mg/kg/day orally) on various biochemical and cardiovascular complications in streptozotocin (STZ) diabetic and deoxycorticosterone acetate (DOCA) hypertensive rats. Female Wistar rats made diabetic or hypertensive or both by streptozotocin (STZ; 45 mg/kg) or deoxycorticosterone acetate (DOCA; 10 mg/kg, p.o., daily) or both. Enalapril (5 mg/kg) was administered daily by the oral route for 6 weeks. At the end of 6 weeks, blood samples were taken to analyze glucose, insulin, and lipids. Blood pressure and heart rate were recorded by a noninvasive technique, and cardiac functions were recorded by Neely's working heart preparation. Injection of STZ produced severe glycosuria (>2%), hyperglycemia, hypoinsulinemia, and loss of body weight. It also produced hypercholesterolemia, hypertriglyceridemia, hypertension, bradycardia, and decreased left ventricular developed pressure (LVDP) and increase in angiotensin-converting enzyme (ACE) in left ventricular tissue. DOCA by itself did not produce any change in blood glucose but reduced serum insulin levels in nondiabetic animals. However, in the diabetic group, DOCA reduced blood sugar levels. Treatment with enalapril prevented an increase in the blood pressure and the heart weight. Decrease in the heart rate, reduction in LVDP, and increase in intracardiac activity were observed in diabetic rats; these were also prevented by enalapril treatment. Enalapril had no effect on plasma glucose and did not modify plasma insulin levels in diabetic animals. The effects of STZ and DOCA together were not additive on the investigated parameters, and enalapril was similarly efficient in diabetic and diabetic hypertensive animals.

Synthesis and antihyperlipaemic activity of some novel N-cyanovinylformamidines.

Potent antihyperlipaemic activity has been observed in a series of novel N-cyanovinylformamidines when tested in hyperlipaemic rats. Two of the compounds (11 and 15) were found more potent than gemfibrozil at 50 mg/kg/d dose level in reducing serum cholesterol and triglyceride levels and also in elevating serum HDL level. A good three-dimensional structural similarity has been observed between these two compounds and clofibrate and gemfibrozil, respectively. Acute toxicity studies carried out in mice indicated compound 11 to be safe even at a dose level of 4.5 g/kg. The title compounds were synthesized by the reaction of alpha-cyanoketene S,N-acetals with formamidineacetate under controlled reaction conditions.

Effect of chronic treatment with atenolol and prazosin in streptozotocin induced diabetic rats.

Diabetes-mellitus was induced in rats by single intravenous injection of (45 mg/kg) streptozotocin (STZ). STZ diabetic rats showed hypertension, decreased cardiac functions, cardiomyopathy and hypercholesterolemia observed at the end of six weeks. Chronic treatment with atenolol (10 mg/kg) for six weeks in the diabetic rats reduced the elevated blood pressure, but failed to prevent STZ induced other complications. Chronic treatment with prazosin (1 mg/kg, po) in the diabetic rats, reduced the elevated blood pressure and also partially prevented hypercholesterolemia, cardiac dysfunctions and in particular the cardiomyopathy. The results suggest that prazosin may be a better option as compared to atenolol in hypertension when it is associated with diabetes mellitus.

High-performance thin-layer chromatography for the determination of cetirizine in human plasma and its use in pharmacokinetic studies.

A rapid and sensitive high-performance thin-layer chromatography (HPTLC) assay has been developed for the measurement of cetirizine in human plasma and its utility for pharmacokinetic study has been evaluated. In the proposed HPTLC method, protein-bound cetirizine was freed by proteolysis of plasma proteins by incubating the plasma with 0.35% pepsin and then extracting with 2 mL pH 5.0 phosphate buffer, followed by 4 mL chilled chloroform. The chloroform layer was separated and concentrated. An aliquot of the extract was then spotted on precoated silica-gel 60 F254 plates using a Camag Linomat IV autosampler. Quantification was with the help of a dual-wavelength TLC scanner. The proposed method had a recovery of 98% and the lowest amount of cetirizine that could be detected was 50 ng. The method was applied for the determination of the plasma levels and pharmacokinetic parameters of cetirizine after oral administration of two marketed preparations in healthy volunteers and the pharmacokinetic parameters determined by the proposed method were in agreement with previously reported values.

Effects of chronic nifedipine treatment on streptozotocin-induced diabetic rats.

We studied the effects of 6-week treatment with nifedipine (35 mg/kg/day orally, p.o.) on streptozotocin (STZ)-induced diabetic rats. Injection of STZ [45 mg/kg intravenously, (i.v.) single dose] produced a significant increase in blood pressure (BP), bradycardia, hyperglycemia, hypoinsulinemia, hyperlipidemia, hypothyroidism, depression in left ventricular developed pressure (LVDP), cardiomyopathy, and nephropathy. Treatment of diabetic rats with nifedipine normalized the BP and prevented bradycardia. Insulin levels were decreased after nifedipine treatment in diabetic as well as nondiabetic rats. However, serum glucose levels were also partially decreased in diabetic animals by nifedipine treatment. In control animals as well, glucose levels were in the normal range despite lower insulin levels observed after nifedipine treatment. Nifedipine treatment significantly prevented STZ-induced increase in cholesterol and triglyceride levels. Nifedipine treatment significantly prevented STZ-induced hypothyroidism and also prevented STZ-induced cardiac depression and cardiomyopathy. Our data indicate that nifedipine increases insulin sensitivity and has some beneficial effects on cardiovascular parameters. It may therefore be considered a preferred drug in the treatment of hypertension associated with diabetes mellitus.