Biomedical subjects

A K Singla

Publications and source records attributed to A K Singla.

At least 19 recordsLinked to original sources

PubMed2006

Comparative bioavailability of a generic capsule formulation of the reverse transcriptase inhibitor efavirenz and the innovator product.

OBJECTIVE: Efavirenz is a non-nucleoside reverse transcriptase inhibitor (NNRTI) that has been used successfully for more than a decade to treat human immunodeficiency virus (HIV) infection. The objective of the current study was to determine the bioequivalence between a generic capsule formulation of efavirenz and the innovator product. MATERIAL AND METHODS: A total of 41 healthy subjects (34 males and 8 females) received a single 200 mg oral dose of efavirenz as the generic (Ranbaxy-Efavirenz, Ranbaxy Laboratories Ltd.) and innovator (Sustiva, Bristol-Myers Squibb) capsule formulations under fasting conditions in a randomized, 2-way crossover study. Multiple blood samples were collected over 72 hours and plasma concentrations of efavirenz were assayed using an LC/MS/MS method. Pharmacokinetic (PK) parameters were calculated using non-compartmental methods. RESULTS: Plasma concentrations of efavirenz peaked within 2.5 hours and then declined in a multi-exponential manner for both formulations. At 72 hours post dose, all plasma concentrations of efavirenz were above the LOQ of the assay (10 ng/ml). Mean area under the curve from 0 - 72 hours (AUC0-72) and maximum plasma concentrations (Cmax) of efavirenz for the generic capsule formulation were 22,840 ng x h/ml and 1,199 ng/ml, respectively. Ratios and 90% confidence intervals of PK parameters between the two formulations were within 80.0 - 125.0%, suggesting that the two capsule formulations resulted in similar rate and extent of bioavailability under fasting conditions. Adverse events were similar in nature and frequency for the two formulations. CONCLUSIONS: Based on the above results, the generic capsule formulation of efavirenz developed by Ranbaxy should be as effective as the innovator product.

Administration, Oral↗

PubMed2006

Comparative bioavailability study of zidovudine administered as two different tablet formulations in healthy adult subjects.

AIM: Zidovudine is a synthetic nucleoside analogue of thymidine with activity against the human immunodeficiency virus type 1 (HIV-1). In patients with HIV infections or the acquired immunodeficiency syndrome (AIDS), zidovudine is a first-line therapy that was shown to reduce morbidity, mortality, and hospitalization. A generic formulation of zidovudine offers the possibility of considerable savings to HIV/AIDS patients in developed and Third World countries. The objective of the current study was to characterize the pharmacokinetic and safety profiles of zidovudine administered as a generic tablet formulation relative to the innovator product. VOLUNTEERS AND METHODS: A total of 68 healthy adult volunteers received a 300 mg oral dose of zidovudine as the generic formulation (AVIRO-Z 300 mg tablet, Ranbaxy Laboratories Limited) and as the innovator product (Retrovir tablet, GlaxoSmithKline) in a randomized, 2-way crossover study. Multiple blood samples were collected over 12 hours and plasma concentrations of zidovudine were assayed using an LC/MS/MS method with an analytical range of 5.00 to 2,000 ng/ml. Pharmacokinetic parameters were calculated using non-compartmental methods. RESULTS: Mean plasma concentrations of zidovudine declined in a mono-exponential manner, with mean concentration values falling below the limit of quantitation 12 hours after administration of both formulations. Mean area under the curve from time 0 to the last measurable concentration (AUC(0-t)), mean area under the curve from time 0 to infinity (AUC(0-infinity)) and peak plasma concentrations (C(max)) of zidovudine for the generic tablet formulation (2,220.6 ng x h/ml, 2,236.0 ng x h/ml and 1,087.9 ng/ml, respectively) were very similar to those observed for the innovator product (2,139.7 ng x h/ml, 2,158.6 ng x h/ml and 1,066.5 ng/ml, respectively). Ratios of least-squares means and 90% confidence intervals of AUC(0-t) AUC(0-infinity) and C(max) between the 2 formulations were within 80-125%, suggesting that the two tablet formulations displayed similar rate and extent of bioavailability. The oral clearance (CL/F) of zidovudine for the generic and innovator formulations were 2.11 1/h/kg and 2.16 1/h/kg, respectively. For the two formulations, adverse events were similar in nature and frequency. CONCLUSION: Since the two formulations displayed similar in vivo delivery rate of zidovudine in the bloodstream, the generic tablet formulation of zidovudine developed by Ranbaxy should be equally effective as the innovator product and is expected to produce considerable cost-savings in AIDS patients worldwide.

Administration, Oral↗

PubMed2006

Nevirapine/lamivudine/stavudine as a combined-formulation tablet: bioequivalence study compared with each component administered concurrently under fasting condition.

OBJECTIVE: The objective of the study was to compare the bioequivalence of a fixed-dose combination of a nevirapine 200 mg, lamivudine 150 mg and stavudine 30 mg combination tablet with application of the 3 medications, at the same dosage, concurrently as separate formulations, in healthy, adult subjects under fasting conditions. MATERIAL AND METHODS: An open-label, balanced, randomized, 2-treatment, 2-period, 2-sequence, single-dose, crossover bioavailability study was conducted in 40 subjects with 21-day washout period between each treatment. Blood samples were collected for 168 hours. Plasma concentrations of nevirapine, lamivudine and stavudine were determined using a validated LC-MS-MS method. Noncompartmental pharmacokinetics and statistical analyses were performed using SAS (SAS Institute Inc., Cary, NC, USA) software (SAS System under Windows, Version 8.02). RESULTS: The ratios of least-square means and the 90% confidence intervals of the log-transformed data were calculated for AUC(0-t), AUC(0-inf), and Cmax. The 90% confidence interval for least-square mean ratio between test and reference formulation for log-transformed parameters Cmax, AUC(0-t) and AUC(0-inf) were within the requirements of the 80-125% range. CONCLUSION: The test formulation (Ranbaxy Laboratories Ltd., Gurgaon, India) is bioequivalent to the reference formulations both in terms of rate and extent of absorption after single-dose administration under fasting condition.

Adolescent↗

PubMed2006

Bioequivalence of abacavir generic and innovator formulations under fasting and fed conditions.

OBJECTIVE: Abacavir sulfate is a synthetic carbocyclic nucleoside analogue indicated for the treatment of HIV-1 infection in combination with other antiretroviral agents. The objective of the current study was to determine the bioequivalence between a generic formulation of abacavir and the innovator product. MATERIAL AND METHODS: A total of 80 subjects were randomly assigned to receive a single 300 mg oral dose of abacavir sulfate as the generic (Ranbaxy-Abacavir, Ranbaxy Laboratories Ltd., equivalent to 300 mg of abacavir) and innovator (Ziagen, GlaxoSmithKline) tablet formulations in 2-way crossover studies performed under fasting (n=40) and fed (n=40) conditions. Multiple blood samples were collected over 14 hours and plasma concentrations of abacavir were assayed using an LC/MS/MS method with a limit of quantitation of 25.0 ng/ml. Pharmacokinetic (PK) parameters were calculated using noncompartmental methods. RESULTS: Under fasting conditions, geometric mean area under the curve from time 0 to the last measurable concentration (AUC(0-t)), area under the curve extrapolated to infinity (AUC(0-infinity) and maximum plasma concentrations (Cmax) of abacavir for the generic (5565 ng x h/ml, 5668 ng x h/ml and 2526 ng/ml, respectively) and innovator (5675 ng x h/ml, 5770 ng x h/ml and 2528 ng/ml, respectively) products were very similar. Under fed conditions, mean values of AUC(0-t) AUC(0-infinity) and Cmax for the generic (4487 ng x h/ml, 4571 ng x h/ml and 1841 ng/ml, respectively) and innovator (4574 ng x h/ml, 4654 ng x h/ml and 1781 ng/ml, respectively) formulations were also very similar. Ratios of LSM and 90% confidence intervals of PK parameters between the 2 formulations were within 80.0 - 125.0% under fasting and fed conditions, suggesting that the 2 tablet formulations resulted in similar rate and extent of bioavailability. Adverse events for the generic and innovator products were similar in nature and frequency in the fasting and fed studies. CONCLUSIONS Based on the above results, the generic tablet formulation of abacavir developed by Ranbaxy should be equally effective as the innovator product.

Adult↗

PubMed2005

Actinoalloteichus spitiensis sp. nov., a novel actinobacterium isolated from a cold desert of the Indian Himalayas.

An actinobacterial strain, RMV-1378T, isolated from a cold desert of the Indian Himalayas, was subjected to polyphasic taxonomic characterization. The strain formed branching, non-fragmenting vegetative hyphae and did not produce diffusible pigments. Neither aerial mycelium nor spore formation was observed. The G+C content of the DNA was 72.0 mol%. The strain had chemotaxonomic characteristics typical of the genus Actinoalloteichus and was closely related (99.3 % 16S rRNA gene sequence similarity) to Actinoalloteichus cyanogriseus, currently the only Actinoalloteichus species with a validly published name. However, the results of DNA-DNA hybridization experiments showed 51.9 % relatedness with the type strain of A. cyanogriseus. On the basis of the above data and the physiological and biochemical distinctiveness of RMV-1378T (=MTCC 6194T=JCM 12472T=DSM 44848T), this strain should be classified as the type strain of a novel species of Actinoalloteichus, for which the name Actinoalloteichus spitiensis sp. nov. is proposed.

Actinomycetales↗

PubMed2004

Chitosan microspheres as a potential carrier for drugs.

Chitosan is a biodegradable natural polymer with great potential for pharmaceutical applications due to its biocompatibility, high charge density, non-toxicity and mucoadhesion. It has been shown that it not only improves the dissolution of poorly soluble drugs but also exerts a significant effect on fat metabolism in the body. Gel formation can be obtained by interactions of chitosans with low molecular counterions such as polyphosphates, sulphates and crosslinking with glutaraldehyde. This gelling property of chitosan allows a wide range of applications such as coating of pharmaceuticals and food products, gel entrapment of biochemicals, plant embryo, whole cells, microorganism and algae. This review is an insight into the exploitation of the various properties of chitosan to microencapsulate drugs. Various techniques used for preparing chitosan microspheres and evaluation of these microspheres have also been reviewed. This review also includes the factors that affect the entrapment efficiency and release kinetics of drugs from chitosan microspheres.

Animals↗

PubMed2004

Release of diltiazem hydrochloride from hydrophilic matrices of polyethylene oxide and carbopol.

The mucoadhesion, swelling, and drug release behavior of polyethylene oxide (PEO) and carbopol (CP) matrices were studied using a water soluble model drug diltiazem hydrochloride. The mucoadhesive strength of the matrices increased with increase in polymer content. The results showed that PEO was more mucoadhesive than CP. Mucoadhesion of the tablets was dependent upon the swelling. Swelling was ascertained by measuring the axial and radial expansion of matrix tablets following exposure to media of physiological ionic strength. There was a marked increase in the swelling index of matrices containing high polymer content of PEO as compared to CP. Drug release kinetics were found to be closely related to dissolution and swelling properties of the matrices. The release was found to be non-Fickian with n (release exponent) values ranging from 0.45-0.58. At a constant polymer content (15.84% w/w), the main contributing factor for the mucoadhesion, swelling, and release was the amount of PEO.

Acrylic Resins↗

PubMed2003

Inhibition of mutagenicity of food-derived heterocyclic amines by sulphoraphene--an isothiocyanate isolated from radish.

The naturally derived isothiocyanate, sulphoraphene [4-isothiocyanato-(1R)-(methylsulphinyl)-1-(E)-butene], isolated from seeds of radish ( Raphanus sativus L., Cruciferae) was investigated for its antigenotoxic effects against a battery of cooked food mutagens (heterocyclic amines) in the Ames Salmonella/reversion assay using Salmonella typhimurium TA98 (frame-shift mutation sensitive) and TA100 (base -pair mutation sensitive) bacterial strains in the presence of Aroclor 1254 induced rat liver S9. Results of the present in vitro anti-mutagenicity studies using the base-pair mutation sensitive strain TA100, strongly suggest that sulphoraphene is a potent inhibitor of the S9-mediated mutagenicity of all the tested heterocyclic amines (60 - 75 % inhibition at a dose of 500 nmol/plate).

Amines↗

PubMed2003

Inhibitory effect of dibenzoylmethane on mutagenicity of food-derived heterocyclic amine mutagens.

Dibenzoylmethane (DBM), a structural analogue of curcumin (a bioactive phytochemical present in a widely used spice turmeric) was screened for its inhibitory effect against seven cooked food mutagens (heterocyclic amines): 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ), 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1), 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2), 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) and 2-amino-6-methyldipyrido[1,2-a:3',2'-d]imidazole (Glu-P-1), in both TA98 and TA100 strains of Salmonella typhimurium using Ames Salmonella/reversion assay in the presence of Aroclor1254-induced rat liver S9 homogenate. DBM has been reported to antagonize the mutagenicity of several chemical carcinogens in vitro and has recently been shown to be even more effective than curcumin in suppressing the 7,12-dimethylbenz[a]anthracene (DMBA)-induced mammary tumors in rats. But there are no reports regarding its antimutagenic properties against cooked food mutagens. Results of the present investigations clearly indicate that dibenzoylmethane is a very potent antimutagenic agent, that could effectively inhibit mutagenicity induced by all the tested cooked food mutagens in both the frame shift (TA98) as well as the base pair mutation sensitive (TA100) strains of S. typhimurium. These highly potent inhibitory effects of dibenzoylmethane against heterocyclic amines observed in our preliminary investigations strongly warrant further studies of its efficacy as a cancer chemopreventive agent.

Amines↗

PubMed2003

Performance liquid chromatographic analysis of glipizide: application to in vitro and in vivo studies.

This paper describes the validation of a sensitive, accurate, and reproducible method for the determination of a release profile of glipizide from controlled-release dosage forms. In this method, an in vitro dissolution profile of commercial controlled-release dosage forms is determined using a reversed-phase C(18) column, mobile phase (acetonitrile-buffer, 0.05 M KH(2)PO(4) adjusted to pH 3.5 with orthophosphoric acid), and UV detection at a wavelength of 275 nm. The method is validated for linearity, accuracy, precision, and detection and quantitation limits. The same method can be exploited to determine the plasma concentration of glipizide. The peak area versus plasma concentration is linear over the range of 12.5-1000 ng/mL and the detection limit was 5 ng/mL in plasma. The average accuracy was 99.90% with a relative standard deviation (RSD) of not more than 3%. Repeatability and reproducibility were found to be good with an RSD of less than 3%.

Chromatography, Liquid↗

PubMed2003

Nifedipine loaded chitosan microspheres prepared by emulsification phase-separation.

A high yield of nifedipine-chitosan microspheres could be obtained using an emulsification phase-separation method. A high level of entrapment of nifedipine in the microspheres was achieved. The microspheres exhibited excellent swelling properties. Differential scanning calorimetry, X-ray diffractometry, and scanning electron microscopy confirmed that at 1.84% loading, nifedipine was dispersed molecularly. The microspheres exhibited faster release at low loadings compared to high loadings. Fitting the data to the coupled Fickian/case II equation, showed that at low loadings polymer relaxation coefficients (k2) were high. As the polymer content increased in the microspheres, the value of n (diffusional exponent characteristic of the release mechanism) approached one, which is indicative of zero order.

Chitin↗

PubMed2002

Liquid chromatographic method for determination of piperine in rat plasma: application to pharmacokinetics.

Piperine, a major alkaloid of Piper longum and Piper nigrum has been reported to have several pharmacological/toxicological effects. Though a number of methods for analysis of this omnipresent food component in pepper fruits are available, its analysis in body fluids has been largely neglected. A high-performance liquid chromatography method for the analysis of piperine in rat plasma is presented in this communication. Analysis was performed using a Symmetry C(18) column (250x4.6 mm) by isocratic elution with 25 mM KH(2)PO(4) (pH 4.5)-acetonitrile (35:65) and UV detection at 340 nm. The calibration plot was linear over the range studied (2-2000 ng) with correlation coefficient of 0.9984. Limit of detection and limit of quantitation were 1 ng/ml and 3 ng/ml, respectively. Good overall recovery (85.5+/-6%) was obtained with 4 ml ethyl acetate and extraction time of 3 min. Intra- and inter-assay coefficient of variation was found to be less than 7.5%. Plasma concentration-time profile of piperine in a conscious rat implanted with jugular vein cannula was obtained using this method. The method is simple, sensitive and reproducible.

Alkaloids↗

PubMed2002

Inhibitory effect of curcumin and its natural analogues on genotoxicity of heterocyclic amines from cooked food.

Curcumin (C) and its natural analogues demethoxycurcumin (dmC) and bisdemethoxycurcumin (bdmC), known for their potent anti-inflammatory, antioxidant, antimutagenic and anticarcinogenic effects, were tested for their possible inhibitory effects against seven cooked food mutagens (heterocyclic amines): 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ), 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1), 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2), 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) and 2-amino-6-methyldipyrido[1,2-a:3',2'-d]imidazole (Glu-P-1), in both TA98 and TA100 strains of Salmonella typhimurium using Ames Salmonella/reversion assay in the presence of Aroclor induced rat liver S9 homogenate. In the present investigations, curcumin as well as its two natural analogues i.e., dmC and bdmC were found to be highly effective in suppressing genotoxicity of all the tested cooked food mutagens in a dose-dependent manner, in both the frame shift (TA98) as well as base pair mutation sensitive (TA100) strains of S. typhimurium. However, bdmC appeared to be a relatively less active antimutagen compared to C and dmC. More than 80% inhibition of mutagenicity was observed at 200 microg/plate in case of C and dmC in both TA98 and TA100 against all tested cooked food mutagens. Where as, bdmC showed 39-79% inhibition in TA100 and 60-80% inhibition in TA98, at a dose of 200 microg/plate. These findings warrant further biochemical, enzymatic and in vivo investigations in animal models as well as in humans to establish the chemoprotective effect of these agents against mutagenic heterocyclic amines found in cooked food.

Amines↗

PubMed2001

Chemistry and pharmacology of the Citrus bioflavonoid hesperidin.

Hesperidin, a bioflavonoid, is an abundant and inexpensive by-product of Citrus cultivation. A deficiency of this substance in the diet has been linked with abnormal capillary leakiness as well as pain in the extremities causing aches, weakness and night leg cramps. No signs of toxicity have been observed with the normal intake of hesperidin or related compounds. Both hesperidin and its aglycone hesperetin have been reported to possess a wide range of pharmacological properties. This paper reviews various aspects of hesperidin and its related compounds, including their occurrence, physical and chemical properties, analysis, pharmacokinetics, safety and toxicity and the marketed products available. A special emphasis has been laid on the pharmacological properties and medicinal uses of these compounds.

Citrus↗

PubMed2001

Piperine inhibits gastric emptying and gastrointestinal transit in rats and mice.

Piperine (1), an alkaloid of black and long peppers, inhibited gastric emptying (GE) of solids/liquids in rats and gastrointestinal transit (GT) in mice in a dose and time dependent manner. Compound 1 significantly inhibited GE of solids and GT at the doses extrapolated from humans (1 mg/kg and 1.3 mg/kg p.o. in rats and mice, respectively). However, at the same dose the effect was insignificant for GE of liquids. One week oral treatment of 1 mg/kg and 1.3 mg/kg in rats and mice, respectively, did not produce a significant change in activity as compared to single dose administration. GE inhibitory activity of 1 is independent of gastric acid and pepsin secretion.

Alkaloids↗

PubMed2001

Antidiarrhoeal activity of piperine in mice.

Peppers are common food ingredients used worldwide. They are also added in traditional antidiarrhoeal formulations of different herbs. Piperine (1) is an alkaloidal constituent of black and long peppers recently established as a bioavailability enhancer of drugs and other substances. As a part of efforts to study its effects on the gastrointestinal tract, the experiments were performed to determine the rationale, if any, for its use in traditional antidiarrhoeal formulations. Antidiarrhoeal activity of 1 against castor oil, MgSO4 and arachidonic acid was studied in mice. It significantly inhibited diarrhoea produced by these cathartics at 8 and 32 mg/kg p.o. dose. Inhibition of castor oil induced enteropooling by 1 suggests its inhibitory effect on prostaglandins. The results validate the rationale for its use in traditional antidiarrhoeal formulations.

Alkaloids↗

PubMed2001

Are women who are Jehovah's Witnesses at risk of maternal death?

OBJECTIVE: The purpose of this study was to determine the rates of obstetric hemorrhage and maternal mortality in women who are Jehovah's Witnesses and to evaluate a protocol that uses erythropoietin to optimize the red blood cell mass before delivery. STUDY DESIGN: Obstetric outcomes were described for all of the women who were Jehovah's Witnesses and who delivered at Mount Sinai Medical Center during an 11-year period. The risk of maternal death was compared with our general obstetric population during this interval. RESULTS: A total of 332 women who were Jehovah's Witnesses had 391 deliveries. An obstetric hemorrhage was experienced in 6% of this population. There were 2 maternal deaths among the women who were Jehovah's Witnesses, for a rate of 512 maternal deaths per 100,000 live births versus 12 maternal deaths per 100,000 live births (risk ratio, 44; 95% CI, 9-211). Erythropoietin was associated with a nonsignificant increase in hematocrit level. CONCLUSION: Women who are Jehovah's Witnesses are at a 44-fold increased risk of maternal death, which is due to obstetric hemorrhage. Patients should be counseled about this risk of death, and obstetric hemorrhage should be aggressively treated, including a rapid decision to proceed to hysterectomy when indicated.

Adult↗

PubMed2001

Chitosan: some pharmaceutical and biological aspects--an update.

Chitosan, a natural polysaccharide, is being widely used as a pharmaceutical excipient. It is obtained by the partial deacetylation of chitin, the second most abundant natural polymer. Chitosan comprises a series of polymers varying in their degree of deacetylation, molecular weight, viscosity, pKa etc. The presence of a number of amino groups permit chitosan to chemically react with anionic systems, thereby resulting in alteration of physicochemical characteristics of such combinations. Chitosan has found wide applicability in conventional pharmaceutical devices as a potential formulation excipient, some of which include binding, disintegrating and tablet coating properties. The polymer has also been investigated as a potential adjuvant for swellable controlled drug delivery systems. Use of chitosan in novel drug delivery as mucoadhesive, gene and peptide drug administration via the oral route as well as its absorption enhancing effects have been explored by a number of researchers. Chitosan exhibits myriad biological actions, namely hypocholesterolemic, antimicrobial and wound healing properties. Low toxicity coupled with wide applicability makes it a promising candidate not only for the purpose of drug delivery for a host of drug moieties (antiinflammatories, peptides etc.) but also as a biologically active agent. It is the endeavour of the present review to provide an insight into the biological and pharmaceutical profile of chitosan. Various investigations carried out recently are reported, although references to research performed on chitosan prior to the recent reviews have also been included, where appropriate.

Animals↗