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Biomedical subjects

M Garg

Publications and source records attributed to M Garg.

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↗
PubMed2004

A prospective randomized trial of percutaneous marrow injection in a series of closed fresh tibial fractures.

We performed a prospective, randomized study on 40 patients with fresh closed fractures of the tibial shaft to determine the effect of autologous bone marrow injection on the union rate. Forty patients were randomized to two injections with 15 ml of autologous bone marrow injections at the fracture site and casting or conventional casting. Fracture union measured by absence of localized tenderness and mobility and bridging of three out of four cortices at the fracture site on plain roentgenograms was assessed at 3, 4, and 5 months of treatment. All fractures receiving bone marrow injections united in 3.65+/-0.49 months; 19/20 fractures treated conventionally united in 4.31+/-0.48 months ( p=0.0004). Other possible determinants of union, complication rates, and cost incurred in the treatment were similar in the two groups.

Adult↗
PubMed2004

Metabolite pattern of Cysticercus cellulosae metacestode from different predilection sites of swine using proton magnetic resonance spectroscopy.

Cysticercosis due to Taenia solium is one of the most common public health problems in various regions of the world. We have performed prolon magnetic resonance spectroscopy (1H MRS) experiments of the fluid aspirated from cysticerci excised from skeletal muscle (n = 16) and brain (n = 9) of infected swine to compare the metabolite pattern of cysticerci in different predilection sites. Perchloric acid extract of cysticercus cysts excised from skeletal muscles (n = 16) was also prepared to ascertain water-soluble, low molecular weight metabolites using 1H MRS. Absolute quantification and statistical analysis of different metabolites was done to look for any significant differences in different locations of cysts. The metabolite pattern of cysticerci was found to be similar in the various predilection sites. Metabolites observed were leucine, valine, alanine, lysine, glycine, lipid contents, lactate, glutamate, acetate, succinate, creatine, choline, and glucose. Concentration of creatine in cysticercus fluid of cysts removed from the muscle was found to be significantly higher (p = 0.001) than the cysts located in the brain. We conclude that the metabolite pattern in the cysticerci is not influenced by the surrounding tissue location; however concentration of certain metabolites may depend upon the tissue location.

Animals↗
PubMed2003

Broad identification of bacterial type from pus by 1H MR spectroscopy.

BACKGROUND: Abscess formation is a common bacterial infection and requires an immediate antimicrobial approach for apposite treatment. Delay in patient treatment is usually a common feature, as the bacterial identification of clinical samples is based on the culture, which is a time-consuming exercise. The current study was aimed at developing an alternative technique with the potential for rapid bacterial group identification. MATERIALS AND METHODS: In the present study we performed ex vivo proton magnetic resonance spectroscopy of 40 pus samples collected from abscesses in different locations and the results have been retrospectively compared with the microorganism identified in the pus culture. In addition, the microbes obtained from the culture have been further subcultured and studied with magnetic resonance spectroscopy to identify the bacterial fingerprint in the pus sample seen on spectroscopy. RESULTS: On reviewing the spectra obtained from the various abscesses, they were found to be qualitatively similar for a particular bacterium. The similar spectral pattern of the pus with obligate aerobes/anaerobes and pure cultures of the same bacteria suggests its strict metabolism under in vivo and in vitro conditions, respectively. CONCLUSIONS: The characteristic metabolite pattern of obligate anaerobes may be used as a prototype for its rapid identification. This information may be of value for more appropriate clinical management of such cases.

Abscess↗
PubMed2002

Demonstration of scolex in calcified cysticercus lesion using gradient echo with or without corrected phase imaging and its clinical implications.

AIM: This study was performed to determine the magnetic resonance imaging (MRI) sequence that was best suited to demonstrate the scolex in a calcified lesion and to seek the explanation for the appearance of a negative phase in a calcified scolex on corrected gradient refocused echo (GRE) phase imaging. MATERIALS AND METHODS: Forty-nine patients with single/multiple computed tomography (CT) documented homogeneous calcified lesions and/or calcified scolices in cysts were studied with conventional spin echo and corrected GRE phase imaging. Calcium and different paramagnetic substances from cysticerci scolices of a sample of infected swine muscle were quantified. RESULTS: The scolex could be demonstrated in 29/39 patients with single calcified lesion. GRE imaging with an echo time of 35ms was the only sequence that demonstrated scolex in all these 29 cases. 15/29 patients with a single calcified lesion, in all 10 patients with multiple calcified lesions and infected swine muscle with multiple cysts and calcified scolex, corrected GRE phase imaging showed negative phase in all these scolices. Estimation of minerals from the calcified scolices from the swine muscle showed by spectroscopic techniques 41.2% of the total mineral contents as paramagnetic substances. CONCLUSION: We conclude that GRE imaging is the imaging method of choice for demonstration of the scolex in a CT calcified lesion. The negative phase on corrected GRE phase imaging is due to the presence of large amount of paramagnetic substances.

Adolescent↗
PubMed2001

Transmyocardial CO(2) laser revascularization improves symptoms, function, and quality of life: 12-month results from a randomized controlled trial.

PURPOSE: To describe differences in health status (symptoms, physical function, and quality of life) between continued medical management and transmyocardial revascularization with a carbon dioxide laser in patients with severe, symptomatic, inoperable coronary artery disease. SUBJECTS AND METHODS: This prospective, multicenter trial randomized 98 patients to transmyocardial revascularization and 99 to continued medical therapy. Health status was assessed with the Seattle Angina Questionnaire and the Short Form-36 at baseline and at 3, 6, and 12 months. A new analytic technique, the benefit statistic, was developed to facilitate interpretability of disease-specific health status assessments over time. RESULTS: Of the 99 patients assigned to medical therapy, 59 (60%) subsequently underwent transmyocardial revascularization. By an intention-to-treat analysis, patients initially randomized to transmyocardial revascularization had 44% of their angina eliminated versus 21% for the medical treatment group (difference = 23%; 95% confidence interval [CI], 11% to 34%). Differences in the benefits of transmyocardial revascularization on physical limitations (33% vs 11% in the medical arm [difference = 23%; 95% CI, 15% to 31%]) and quality of life (47% vs 20% in the medical arm [difference = 26%; 95% CI, 18% to 35%]) were similarly large. These benefits were apparent at 3 months and sustained throughout the 1 year of follow-up. An efficacy analysis that excluded patients who crossed over from the medical treatment to transmyocardial revascularization arm suggested greater treatment benefits. CONCLUSIONS: Transmyocardial revascularization may offer a valuable palliative alternative to patients with severe limitations in health status for whom no standard revascularization options exist.

Angina Pectoris↗
PubMed2001

Native aortic valve tissue systemic embolization complicating bacterial endocarditis.

Systemic embolic events are known complications of bacterial endocarditis. Embolization of prosthetic valves has previously been reported in the literature. We report a case of embolization of native aortic valve tissue to the popliteal artery as the presenting event in a patient with subacute bacterial endocarditis. To our knowledge, this rare complication has not been previously reported.

Adult↗
PubMed2001

Dorsal free graft urethroplasty for urethral stricture by ventral sagittal urethrotomy approach.

OBJECTIVES: To explore the feasibility of applying a dorsal free graft to treat urethral stricture by the ventral sagittal urethrotomy approach without mobilizing the urethra. METHODS: Twelve patients with long or multiple strictures of the anterior urethra were treated by a dorsal free full-thickness preputial or buccal mucosa graft. The urethra was not separated from the corporal bodies and was opened in the midline over the stricture. The floor of the urethra was incised, and an elliptical raw area was created over the tunica on which a free full-thickness graft of preputial or buccal mucosa was secured. The urethra was retubularized in one stage. RESULTS: After a follow-up of 8 to 40 months, one recurrence developed and required dilation. CONCLUSIONS: The ventral sagittal urethrotomy approach for dorsal free graft urethroplasty is not only feasible and successful, but is easy to perform.

Adolescent↗
PubMed2001

Treatment of relapse after allogeneic bone marrow transplantation with reduced intensity conditioning (FLAG +/- Ida) and second allogeneic stem cell transplant.

Acute leukaemias in relapse after allogeneic stem cell transplantation (SCT) respond poorly to donor leucocyte infusions (DLI) compared with chronic myeloid leukaemia (CML), at least in part because of faster disease kinetics. Fludarabine-containing 'non-myeloablative' chemotherapy followed by further allo SCT may offer more rapid and effective disease control. We report 14 patients with relapse after allo SCT for acute leukaemia [seven acute myeloid leukaemia (AML), five acute lymphoblastic leukaemia (ALL)] or refractory anaemia with excess blasts in transformation (RAEB-t, n = 2) treated with fludarabine, high-dose cytosine arabinoside (ara-C) and granulocyte colony-simulating factor (G-CSF) with (n = 10) or without (n = 2) idarubicin (FLAG +/- Ida) or DaunoXome (FLAG-X) (n = 2) and second allo SCT from the original donor. Donors were fully human leucocyte antigen (HLA) -matched in 13 cases with a single class A mismatch in one. Actuarial overall survival was 60% and disease-free survival was 26% at 58 months. Remissions after the second SCT were longer than those after the first bone marrow transplantation (BMT) in eight of the 13 assessable patients to date. Haematopoietic recovery was rapid. Transplants were well tolerated with no treatment-related deaths. The major complication was graft-versus-host disease (GvHD, acute >/= grade II-2 cases, chronic - eight cases, two limited, six extensive) although there have been no deaths attributable to this. FLAG +/- Ida and second allo SCT is a safe and useful approach and may be more effective than DLI in the treatment of acute leukaemias relapsing after conventional allo SCT.

Acute Disease↗
PubMed2001

Determinants of mortality after myocardial infarction in patients with advanced renal dysfunction.

Previous studies using administrative data have shown high mortality in patients with renal failure requiring dialysis after acute myocardial infarction (AMI). There has been little investigation into the mortality after AMI in those with advanced renal disease who are not on dialysis therapy. We analyzed a prospective coronary care unit registry of 1,724 patients with ST segment elevation myocardial infarction admitted over an 8-year period at a single tertiary-care center. Those not on chronic dialysis therapy were stratified into groups based on corrected creatinine clearance, with cutoff values of 46.2, 63.1, and 81.5 mL/min/72 kg. Dialysis patients (n = 47) were considered as a fifth comparison group. Older age, black race, diabetes, hypertension, previous coronary disease, and heart failure were incrementally more common across increasing renal dysfunction strata. There were also graded increases in the relative risk for atrial and ventricular arrhythmias, heart block, asystole, development of pulmonary congestion, acute mitral regurgitation, and cardiogenic shock. Primary angioplasty, thrombolysis, and beta-blockers were used less often across the risk strata (P < 0.0001 for all trends). There was an early mortality hazard (age-adjusted relative risk, 8.76; P < 0.0001) for those with renal dysfunction but not on dialysis therapy for the first 60 months, followed by graded decrements in survival across increasing renal dysfunction strata. The excess mortality in this population appears to be mediated through arrhythmias, adverse hemodynamic events, and the lower use of mortality-reducing therapy.

Adult↗
PubMed2001

Allogeneic stem-cell transplantation for lymphoproliferative disorders using BEAM-CAMPATH (+/- fludarabine) conditioning combined with post-transplant donor-lymphocyte infusion.

BACKGROUND: We report our updated experience of allogeneic transplantation in lympho-proliferative disorders using a reduced-intensity conditioning regimen combining BEAM (plus fludarabine in three cases) with pre-transplant CAMPATH. Post-transplant donor lymphocytes have been infused for persisting disease or relapse, and both chimerism and minimal residual disease have been monitored utilizing molecular techniques. METHODS: Thirty patients with median age 47.6 years underwent allogeneic transplantation for relapsed or high-risk lymphoproliferative disease using HLA-identical (sibling n = 25, unrelated n = 2) or one antigen mismatched sibling donors (n = 3). Twenty-one had NHL, three had HD and six had CLL/PLL. Stem-cell source was PBSC (n = 24), BM (n = 5) or both (n = 1) with a median CD34 dose of 4.5 x 10(6)/kg. GvHD prophylaxis was with CYA and MTX. RESULTS: Engraftment was prompt in the majority of patients, with a median of 15 days to both ANC > 0.5 and platelets > 20. There have been three transplant-related deaths secondary to viral pneumonitis or bacterial pneumonia. Seven patients developed Grade I-II acute GvHD post-transplant. Of 28 evaluable patients, 18 achieved a CR at assessment 2-3 months post-transplant and a further patient converted from PR to CR following DLI, to give an overall CR rate of 68%. Three patients had early progressive disease and six have relapsed from CR or progressed from PR (two of whom have achieved CR following DLI therapy). Overall survival is 67% and event-free survival 48% at 3 years. With a median follow-up of 1.3 years 57% of patients are currently alive and lymphoma-free. A molecular remission has been achieved in nine of 12 informative patients. DISCUSSION: These encouraging results show that this reduced-intensity conditioning regimen is effective, with a low-toxicity profile compared with conventional TBI-based conditioning, and certainly merits further evaluation in this setting.

Adolescent↗