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G Balan

Publications and source records attributed to G Balan.

At least 19 recordsLinked to original sources
PubMed2005

Rational selection of structurally diverse natural product scaffolds with favorable ADME properties for drug discovery.

Natural product analogs are significant sources for therapeutic agents. To capitalize efficiently on the effective features of naturally occurring substances, a natural product-based library production platform has been devised at Aurigene for drug lead discovery. This approach combines the attractive biological and physicochemical properties of natural product scaffolds, provided by eons of natural selection, with the chemical diversity available from parallel synthetic methods. Virtual property analysis, using computational methods described here, guides the selection of a set of natural product scaffolds that are both structurally diverse and likely to have favorable pharmacokinetic properties. The experimental characterization of several in vitro ADME properties of twenty of these scaffolds, and of a small set of designed congeners based upon one scaffold, is also described. These data confirm that most of the scaffolds and the designed library members have properties favorable to their utilization for creating libraries of lead-like molecules.

Alkaloids↗
PubMed2001

In vitro-in vivo correlation (IVIVC) models for metformin after administration of modified-release (MR) oral dosage forms to healthy human volunteers.

The objective of the current study was to develop and evaluate the internal predictability for level C and A in vitro-in vivo correlation (IVIVC) models for prototype modified-release (MR) dosage forms of metformin. In vitro dissolution data for metformin were collected for 22 h using a USP II (paddle) method. In vivo plasma concentration data were obtained from 8 healthy volunteers after administration of immediate-release (IR) and MR dosage forms of metformin. Linear level C IVIVC models were developed using dissolution data at 2.0 and 4.0 h and in vitro mean dissolution time (MDT). A deconvolution-based level A model was attempted through a correlation of percent in vivo input obtained through deconvolution and percent in vitro dissolution obtained experimentally. Further, basic and extended convolution level A IVIVC models were attempted for metformin. Internal predictability for the IVIVC models was assessed by comparing observed and predicted values for C(max) and AUC(INF). The results suggest that highly predictive level C models with prediction errors (%PE) of <5% could be developed. Mean percent in vivo input for metformin was incomplete from all formulations and did not exceed 35% of dose. The deconvolution-based level A models for all MR formulations were curvilinear. However, a unique IVIVC model applicable to all MR formulations could not be developed using the deconvolution approach. The basic convolution level A model, which used in vitro dissolution as the in vivo input, had %PE values as high as 103%. Using an extended convolution approach, which modeled the absorption of metformin using a Hill function, a level A IVIVC model with %PE as low as 11% was developed. In conclusion, the current work indicates that level C and A IVIVC models with good internal predictability may be developed for a permeability- and absorption window-limited drug such as metformin.

Administration, Oral↗
PubMed2000

In-vitro in-vivo correlation models for glibenclamide after administration of metformin/glibenclamide tablets to healthy human volunteers.

In this study, level C and A in-vitro in-vivo correlation (IVIVC) models were developed for glibenclamide. In-vitro dissolution data were collected for the glibenclamide component of three metformin/glibenclamide tablets using a USP Type II apparatus. In-vivo plasma concentration data were obtained after administration of the prototype formulations to 24 healthy volunteers and subject to deconvolution analysis to obtain percentage in-vivo absorbed profiles. Multiple linear level C models were developed for CMAX and AUC(0-48) using percentage in-vitro dissolved data at 10, 45 and 120 min. Initially, the level A model was constructed for the first 2 h only, based on availability of in-vitro data. Another level A model was attempted using a time-scaled approach, with percentage in-vivo absorbed at time t and percentage in-vitro dissolved at time t/I as the correlating data. Internal predictability was evaluated for the level C and time-scaled level A models. For all level C approaches, linear regression models with r2 > 0.99 were determined. The prediction errors (% PE) for Cmax and AUC(0-48) were less than 1% for all formulations at all three chosen time points. The deconvolution analysis indicated biphasic absorption for glibenclamide, with one phase occurring at 2-3h and another at 6-12h after dose administration. The level A model using 2-h data was not unique for all formulations and was therefore not developed. The time-scaling factor I correlated highly (r2 = 0.99) with in vitro mean dissolution time (MDT). A linear regression time scaled model (r2 = 0.97) was successfully developed using in-vitro and in-vivo data from all 3 formulations. However, the internal predictability of the time-scaled model was poor, with % PE values for Cmax and AUC(0-48) being as much as 30.5% and 18.7%, respectively. The results indicate that level C models have good internal predictability. Though a time-scaled level A IVIVC model was successfully developed, the model was found to have poor internal predictability.

Adult↗
PubMed1996

Bioequivalence of two tablet formulations of nadolol using single and multiple dose data: assessment using stereospecific and nonstereospecific assays.

Nadolol, a nonspecific beta-blocker, is a racemate composed of equal amounts of four stereoisomers, namely, SQ-12148, SQ-12149, SQ-12150, and SQ-12151. In an open-label, randomized, four-period crossover study, the pharmacokinetics of nadolol and its stereoisomers and the bioequivalence of two formulations of nadolol were assessed in 20 healthy male subjects following a single dose (80 mg) and multiple doses (80 mg; once daily for 7 days). A standard granulated tablet and direct compressed tablet formulations, each containing 80 mg of nadolol, with different in vitro dissolution profiles that met current USP requirements were used. The four treatments were single and multiple doses of granulated tablet, and single and multiple doses of compressed tablet. There was a 7 day washout period between successive treatments. All doses of nadolol were administered after an overnight fast. Serial blood samples were collected up to 72 h following the single dose and during multiple dose treatments, following day 6 and 7 doses. Validated high-performance liquid chromatographic assays were applied to measure nadolol and its stereoisomers in the study samples. Plasma concentration data were subjected to noncompartmental pharmacokinetic analysis. Both C(max) and AUC values were significantly greater for SQ-12150 when compared to other nadolol stereoisomers obtained after a single dose or at steady state. However, T(max) and T1/2 values were similar among the four isomers. The observed steady state AUC tau values for nadolol (2278-2331 ng h/ML) or its stereoisomers (550-874 ng h/ML) were significantly greater than those predicted from the single dose AUCinf values (nadolol, 1840-1845 ng h/ML; isomers, 450-713 ng h/ML). The intrasubject variability, computed from multiple dose data, was generally greater for the stereoisomers (17-40%) than for nadolol (10-32%). The two formulations were bioequivalent for nadolol (C(max) = 0.98 [84%, 117%]; AUCinf = 1.03 [93%, 116%]) and SQ-12150 (C(max) = 1.12 [89%, 122%]; AUCinf = 0.98 [82%, 119%]) after a single dose, and only for nadolol (C(max) = 1.07 [84%, 118%]; AUCinf = 1.02 [91%, 113%]) at steady state.

Adult↗
PubMed1975

A renin-like activity in pineal gland and hypophysis.

The presence and distribution of renin-like activity in hypophysis, pineal gland and some neural tissues were studies in both normal and salt-loaded rats. The Boucher micromethod was used to detect enzymatic activity. In normal rats both the pituitary and pineal glands contained significantly higher values of renin-like activity than did the other tissues examined. In salt-loaded animals there was a significant decrease of the renin-like activity of the glandular tissue while in the other brain areas the activity increased. The results are discussed in terms of the possible physiological role of the central renin-angiotensin system in the regulation of fluid and electrolyte balance.

Animals↗
PubMedDate not supplied

[Klatskin's tumor].

During the period 1989-1998, 27 patients with primary proximal bile duct cancer were treated (17 females and 10 males with a mean age of 61 years). The main presenting symptoms were: jaundice (96.2%), itching (92.5%), weight loss (74%) and atypical pain (33.3%). All the patients underwent ultrasound (US) examination, 7 patients endoscopic retrograde cholangiopancreatography (ERCP) and 4 patients computed tomography (CT) examination. US examination revealed the tumor in 51% cases; most frequently a dilatation of the intrahepatic bile ducts was diagnosed with all methods. 8 patients underwent resection of the tumor and one a biliary-enteric anastomosis, in 15 cases a stent was inserted. In 3 cases the extension of the malignancy did not allowed any procedure. Three patients died during immediate postoperative period (mortality 11.2%). The mean survival was 13 months after stenting and 22 months after resection of the tumor. The authors recommended an aggressive surgical therapy for Klatskin tumors.

Adult↗
PubMedDate not supplied

Pancreatic enzymes replacement therapy in chronic pancreatitis: an update.

Chronic pancreatitis is the major cause of exocrine pancreatic insufficiency which should be compensated by pancreatic enzyme replacement therapy. There are now available a great number of pancreatic enzyme preparations, but encapsulated enteric-coated microspheres and minimicrospheres are considered the enzyme treatment of choice. However, full compensation of pancreatic exocrine insufficiency with enzyme replacement therapy cannot be obtained in all patients with chronic pancreatitis.

Chronic Disease↗
PubMedDate not supplied

[The value of the echographic exam in the diagnosis of intra-abdominal "textilomas"].

In the absence of radioopaque marker, the diagnosis of textiloma, a rare iatrogenic lesion, is difficult. The wide use of abdominal ultrasonography significantly improved the preoperative diagnosis, the most typical image being that of a echogenic area with a posterior shadow cone. Nine cases of intraabdominal textiloma, in the diagnosis of which ultrasound played the most intra-abdominal textiloma, in the diagnosis of which ultrasound played the most important role, are presented. Although the ultrasound image is not specific, it is nevertheless enough suggestive the diagnosis of textiloma and thus for indicating an early surgery, before complications occur.

Abdomen↗
PubMedDate not supplied

De-Nol in the treatment of reflux esophagitis.

Twenty-eight patients with histologically proven reflux esophagitis were randomly allocated to receive either De-Nol (tripotassium dicitrate bismuthate) or placebo for three weeks. Significant decreases in symptoms frequency and severity were noted in De-Nol group comparing with placebo group (p less than 0.01). Objective improvement in esophageal endoscopic appearance was obtained in 78.5% of the patients treated with De-Nol and only in 14.2% of those receiving placebo. De-Nol appears to be an effective drug in the treatment of reflux esophagitis, but this should be confirmed by further studies.

Adult↗
PubMedDate not supplied

Continuous electrocardiographic monitoring during balloon dilatation in achalasia.

Electrocardiographic (ECG) changes in nine patients under continuous ECG monitoring before, during and after balloon dilatation for achalasia were followed; of these, three had ischaemic heart disease (IHD). One or several abnormalities including sinus tachycardia, supraventricular or ventricular ectopic beats, S-T segment depression and T-wave flattening appeared during the procedure; these were more commonly found in patients with IHD. Despite the high incidence of recorded ECG abnormalities, these were transient, and no treatment was needed. However, it seems advisable to have resuscitation equipment and emergency drugs available during balloon dilatation for achalasia, particularly when this procedure is performed in patients with IHD.

Adult↗