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Biomedical subjects

T P Gandhi

Publications and source records attributed to T P Gandhi.

At least 19 recordsLinked to original sources
PubMed2000

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.

Acyclovir↗
PubMed1998

High performance thin-layer chromatographic method for the determination of sparfloxacin in human plasma and its use in pharmacokinetic studies.

A rapid and sensitive high-performance thin-layer chromatographic (HPTLC) method has been developed for the measurement of sparfloxacin in human plasma and its use for pharmacokinetic study has been evaluated. Detection and quantitation were performed without using an internal standard. A single stage extraction procedure was followed for extracting sparfloxacin from plasma and a known amount of the extract was spotted on precoated silica gel 60 F254 plates using a Camag Linomat IV autosampler. Sparfloxacin was quantified using a Camag TLC Scanner 3. The recovery study of authentic analytes added to plasma at 0.1 to 0.8 microgram ml-1 was 94.9 +/- 0.98% and the lowest amount of sparfloxacin that could be detected was 50 ng ml-1 plasma. The method provides a direct estimate of the amount of sparfloxacin present in plasma. The method was used for the determination of plasma levels as well as pharmacokinetic parameters of sparfloxacin after oral administration of two marketed preparations to healthy volunteers.

Administration, Oral↗
PubMed1998

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.

Analysis of Variance↗
PubMed1997

High-performance thin-layer chromatographic method for the detection and determination of lansoprazole in human plasma and its use in pharmacokinetic studies.

A rapid and sensitive high-performance thin-layer chromatography (HPTLC) method has been developed for the measurement of lansoprazole in human plasma and its use for pharmacokinetic study has been evaluated. Detection and quantitation were performed without using an internal standard. A single stage extraction procedure was followed for extracting lansoprazole from plasma and a known amount of the extract was spotted on precoated silica gel 60 F254 plates using a Camag Linomat IV autosampler. Lansoprazole was quantified using a Camag TLC Scanner 3. The recovery study of authentic analytes added to plasma at 0.05 to 0.25 microg/ml was 95.37+/-2.15% and the lowest amount of lansoprazole that could be detected was 20 ng/ml plasma. The method provides a direct estimate of the amount of lansoprazole present in plasma. The method was used for the determination of plasma levels as well as pharmacokinetic parameters of lansoprazole after oral administration of two marketed preparations to healthy volunteers.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1997

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

A rapid and sensitive high-performance thin-layer chromatographic assay has been developed for the measurement of nimesulide in human plasma. Its use for pharmacokinetic studies has been evaluated. The method includes a single-stage extraction procedure without the use of an internal standard. Analysis was performed on plasma containing known amounts of the drug, on drug-free plasma, and on plasma containing an unknown quantity of the drug. Known amounts of extract and nimesulide (100 and 200 ng, as external standard) were spotted on precoated silica-gel 60F254 plates by means of a Camag Linomat IV autosampler. Quantification was achieved using a Camag TLC scanner 3. The recovery of the method was 97.10 +/- 2.22%. The method was applied for the determination of plasma levels and pharmacokinetic parameters of nimesulide after oral administration of two formulations (100 mg) in healthy volunteers. The method is a sensitive, economical, rapid and specific assay for nimesulide in human plasma, and is suitable for pharmacokinetic studies after therapeutic doses.

Administration, Oral↗
PubMed1997

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.

Animals↗
PubMed1996

Sensitive high-performance thin-layer chromatography method for detection and determination of ranitidine in plasma samples.

A high-performance thin-layer chromatographic procedure has been developed for the determination of ranitidine, a H2-receptor antagonist, in plasma. The detection and quantification were performed without using internal standards. A single-stage extraction procedure was followed for extracting ranitidine from plasma, and a known amount of the extract was spotted on precoated silica gel F254 plates. Ranitidine was quantified using a Shimadzu CS930 dual-wavelength TLC scanner. The method provides a direct estimate of total ranitidine present in the plasma.

Adult↗
PubMed1996

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.

Adult↗
PubMed1996

Effect of chronic treatment with hydralazine on various in vitro preparations of rat.

Effect of chronic treatment with hydralazine (40 mg/kg/day) on isolated heart, anococcygeus muscle and myometrial preparations from rats has been studied. The treatment for 6 weeks caused a significant increase in isoprenaline induced positive inotropic response in rat heart. However, isoprenaline induced positive chronotropic effects were not altered significantly by chronic hydralazine treatment. Chronic hydralazine treatment also failed to alter noradrenaline induced contractile effects on rat anococcygeus muscle. However, on myometrial preparations from hydralazine treated rats showed an increase in adrenaline induced relaxations. The results of the present study can be explained on the basis of the effect of hydralazine on adenylate cyclase-cyclic adenosine monophosphate (cAMP).

Animals↗
PubMed1996

Synthesis and quantitative structure-activity relationships of antihyperlipaemic 2-substituted thieno[3,2-d]pyrimidin-4(3H)-ones.

The synthesis, antihyperlipaemic evaluation and quantitative structure-activity relationships (QSAR) of two series of thieno[3,2-d]pyrimidin-4-one derivatives are reported. While most of the compounds in these series were found to exhibit antihyperlipaemic activity, the QSAR study of these two series indicated a positive influence of only the electronic nature of the 2-substitutents on the biological activity. The lipophilic and the steric parameters did not appear to be significant.

Animals↗
PubMed1995

Detection and determination of total amlodipine by high-performance thin-layer chromatography: a useful technique for pharmacokinetic studies.

A novel analytical method for determination of the total plasma levels (free and protein bound) of the calcium channel blocking agent amlodipine has been developed using a high-performance thin-layer chromatographic (HPTLC) procedure. Detection and quantitation were performed without internal standards. In previously described methods for the estimation of amlodipine by gas chromatography and high-performance liquid chromatography, only the free levels in plasma and serum were quantified at 7% of the total amlodipine level, with the remaining 93% bound to plasma protein and tissue. The present method employs proteolysis of the plasma proteins by incubating plasma for 2 h in pepsin solution. After proteolysis amlodipine is extracted and a known amount of the extract is spotted on precoated silica-gel 60 F254 plates using a Camag Linomat IV autosampler. Amlodipine was quantified using a dual-wavelength TLC scanner. The method provides a direct estimate of the total amlodipine present in plasma.

Amlodipine↗
PubMed1995

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.

Administration, Oral↗
PubMed1994

Pharmacokinetics of gentamicin in rabbits pretreated with nonsteroidal anti-inflammatory drugs: an interaction study.

Interaction between nonsteroidal anti-inflammatory drugs (NSAIDs) and other drugs occurs relatively frequently because of the wide use of NSAIDs. Such interactions with drugs of narrow therapeutic index used in serious disease states may lead to toxicity. Gentamicin toxicity is based on its concentration in serum, and any alteration in pharmacokinetic parameters may lead to gentamicin accumulation in the body and subsequently to severe nephrotoxicity and ototoxicity. To test this hypothesis, the effect of pretreatment with NSAIDs on gentamicin pharmacokinetics was examined in rabbit. Gentamicin sulfate (5 mg/kg) was administered to rabbits pretreated with aspirin (300 mg/kg), ketorolac tromethamine (3 mg/kg), ibuprofen (20 mg/kg), and piroxicam (2 mg/kg) twice a day for 1 week. The pretreatment with NSAIDs had significant effects on the body clearance and maximum concentration. Aspirin, piroxicam and ketorolac tromethamine pretreatment had significant effects on the area under the curve of gentamicin versus time. Aspirin and ketorolac tromethamine pretreatment had significant effects on the half-life of gentamicin. Aspirin had a significant effect on the volume of distribution of gentamicin. These results suggest that pretreatment with NSAIDs alters the pharmacokinetics of gentamicin and leads to accumulation inside the body, which could result in toxicity.

Animals↗
PubMed1991

Detection and determination of free and plasma protein-bound astemizole by thin-layer chromatography: a useful technique for bioavailability studies.

A thin-layer chromatographic (TLC) procedure has been developed for the determination of astemizole in plasma as the free and as protein-bound substance. The detection and quantification were performed without using internal standards. In earlier described methods for the estimation of astemizole by high-performance liquid chromatography and radioimmunoassay, only free levels in plasma were quantified, at 3.3% of the total astemizole, with the remaining 96.7% bound to plasma protein and tissue. Our method employs proteolysis of plasma proteins by incubating plasma for 2 h in pepsin. After proteolysis the astemizole is extracted, and a known amount of the extract is spotted on precoated silica gel F 254 plates. Astemizole was quantified using a Shimadzu CS-930 dual-wavelength TLC scanner. The method provides a direct estimate of total astemizole present in the plasma.

Animals↗
PubMed1990

Synthesis and pharmacological study of antihyperlipaemic activity of 2-substituted thieno(2,3-d)pyrimidin-4(3H)-ones.

A series of 2-substituted thieno(2,3-d)pyrimidin-4-(3H) ones (1-15) was prepared by the reaction of thiophene ortho-aminoester (IV) with a variety of nitriles (V) under acidic conditions, and screened for antihyperlipaemic activity in various animal models. While most of these compounds were found active, 2-chloromethyl-5,6,7,8-tetrahydrobenzo(b)thieno(2,3-d) pyrimidin-4(3H)-one (5) was found to be the most active of all. The serum triglyceride lowering activity exhibited by 5 was found comparable to that of clofibrate and riboflavin tetrabutyrate. Compound 5 was also found to be safe as indicated by acute and chronic toxicity studies in mice and rats.

Animals↗
PubMed1989

Nifedipine and blood glucose in normal human volunteers.

The effect of nifedipine, a calcium antagonist on fasting blood glucose level, glucose tolerance, glucose-induced insulin and glucagon secretion was studied in healthy nondiabetic volunteers. Nifedipine 10mg twice daily for four weeks did not affect fasting blood glucose level, glucose tolerance, glucose-induced insulin and glucagon secretion.

Adult↗
PubMed1987

Calcium antagonists and blood glucose in normal rabbits.

The effects of the calcium antagonists verapamil and nifedipine on blood glucose levels, glucose tolerance, insulin secretion during glucose tolerance and hypoglycaemic effect of tolbutamide were studied in normal nondiabetic rabbits. Daily dosage of 40 mg/kg verapamil and 5 mg/kg nifedipine given orally up to 7 days did not affect blood glucose level, glucose tolerance, insulin secretion during glucose tolerance and hypoglycaemic activity of tolbutamide 250 mg/kg p.o.

Animals↗