An Open-Label, Single-Period, Two-Stage, Single Oral Dose Pharmacokinetic Study of Remogliflozin Etabonate Tablet 100 and 250 mg in Healthy Asian Indian Male Subjects Under Fasting and Fed Conditions.

BACKGROUND AND OBJECTIVE: Remogliflozin etabonate is an orally available prodrug of remogliflozin, an inhibitor of renal sodium glucose co-transporter-2 (SGLT2) with antihyperglycemic activity. The present study was conducted to characterize the pharmacokinetic and safety profile of remogliflozin etabonate under fasting and fed conditions at single oral doses of 100 and 250 mg in healthy Asian Indian adults. METHODS: Sixty-five healthy, adult Asian Indian male subjects were enrolled in an open-label, two-stage, single-period pharmacokinetic study. Remogliflozin was given under fasting and/or fed conditions as a single oral dose of 100 or 250 mg. The plasma concentrations of remogliflozin etabonate, remogliflozin, and the metabolite GSK279782 were quantified by validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. Pharmacokinetic parameters were determined from the plasma concentration-time profile by non-compartmental analysis. Safety was assessed through monitoring of adverse events. Descriptive statistics were calculated and reported for all parameters. RESULTS: The plasma concentration profiles showed rapid absorption of the prodrug remogliflozin etabonate and rapid conversion to the active moiety, remogliflozin, which is then further metabolized to another active metabolite, GSK279782. The geometric mean maximum concentration (Cmax) and area under the plasma concentration-time curve (AUC) were comparable for all three analytes between the fasted and fed state. The fed/fasted ratio for Cmax ranged from 0.77 to 1.44 at the 100 mg dose, and from 0.80 to 1.12 at the 250 mg dose. The fed/fasted ratio for AUC was 1.22 and 1.35 at 100 and 250 mg, respectively. An early time to Cmax (tmax) was observed for all three analytes while being administered in the fasted state. Both the Cmax and AUClast of all the three analytes increased in a dose-proportional manner under the fasted and fed states. The terminal half-life for remogliflozin ranged from 1.53 to 2.07 h. All three analytes had comparable terminal half-lives irrespective of dose levels or dietary conditions. CONCLUSIONS: Following single oral administration at 100 and 250 mg, remogliflozin etabonate showed favorable, linear pharmacokinetics. There were no clinically relevant food effects on the pharmacokinetics at both the 100 and 250 mg dose levels. Remogliflozin etabonate was well-tolerated without any safety concerns or hypoglycemic events. CLINICAL TRIAL REGISTRATION: Clinical Trial Registry-India identifier number CTRI/2017/10/010043.

Comparison between the Baska Mask® and I-Gel for Minor Surgical Procedures Under General Anaesthesia.

OBJECTIVE: Minor surgical procedures under general anaesthesia require a patent airway without the use of muscle relaxant. Supraglottic airway devices have been widely used for airway management. A study was undertaken to compare first-time insertion success rate, insertion time, sealing pressure and complications between the Baska® mask and I-gel. METHODS: After approval from the institutional ethical committee, a randomised single-blinded study was conducted on 50 American Society of Anesthesiologists' physical status I and II female patients aged 18-40 years who underwent minor surgical procedures under general anaesthesia. Patients were randomly categorized into two groups of 25 each; group Baska® mask and group I-gel, and the first-time success rate, mean insertion time and sealing pressure were measured. The results were analysed using unpaired t-test, Mann-Whitney U test, Chi-square test and ANOVA. A p value <0.05 was considered to be statistically significant. RESULTS: The first-time insertion success rate of the Baska® mask was 21/24 (88%) when compared with the I-gel, which was 23/25 (92%) (p=0.585). The insertion time of the Baska® mask was 14.9±6.2 s, whereas that of the I-gel was 14.7±4.4 s (p=0.877). The mean sealing pressure of the Baska® mask was significantly higher when compared with the I-gel (28.9±3.5 vs. 25.9±2.5 cmH2O) (p=0.001). CONCLUSION: The Baska® mask had a similar first-time insertion success rate and insertion time as the I-gel. The sealing pressure of the Baska® mask was significantly greater than that of the I-gel. Both devices had complications that were comparable.

Peripheral venous pressure as a reliable predictor for monitoring central venous pressure in patients with burns.

BACKGROUND: Optimizing cardiovascular function to ensure adequate tissue oxygen delivery is a key objective in the care of critically ill patients with burns. Hemodynamic monitoring may be necessary to optimize resuscitation in serious burn patients with reasonable safety. Invasive central venous pressure (CVP) monitoring has become the corner stone of hemodynamic monitoring in patients with burns but is associated with inherent risks and technical difficulties. Previous studies on perioperative patients have shown that measurement of peripheral venous pressure (PVP) is a less invasive and cost-effective procedure and can reliably predict CVP. OBJECTIVE: The aim of the present prospective clinical study was to determine whether a reliable association exists between changes in CVP and PVP over a long period in patients admitted to the Burns Intensive Care Unit (BICU). SUBJECTS AND METHODS: The CVP and PVP were measured simultaneously hourly in 30 burns patients in the BICU up to 10 consecutive hours. The predictability of CVP by monitoring PVP was tested by applying the linear regression formula and also using the Bland-Altman plots of repeated measures to evaluate the agreement between CVP and PVP. RESULTS: The regression formula revealed a reliable and significant association between CVP and PVP. The overall mean difference between CVP and PVP was 1.628 ± 0.84 mmHg (P < 0.001). The Bland-Altman diagram also showed a perfect agreement between the two pressures throughout the 10 h period. CONCLUSION: Peripheral venous pressure measured from a peripheral intravenous catheter in burns patients is a reliable estimation of CVP, and its changes have good concordance with CVP over a long period of time.

Effect of progesterone on phosphamidon-induced impairment of memory and oxidative stress in rats.

Progesterone (a neurosteroid) is an important modulator of the nervous system functioning. Organophosphorus pesticides like phosphamidon have been shown to adversely affect memory and induce oxidative stress on both acute and chronic exposure. The present study was therefore designed to investigate the effects of progesterone (PROG) on phosphamidon-induced modulation of cognitive function and oxidative stress in rats. Cognitive function was assessed using step-down latency (SDL) on a passive avoidance apparatus and transfer latency (TL) on an elevated plus maze. Oxidative stress was assessed by examining the levels of thiobarbituric acid reactive species (TBARS) and non-protein thiols (NP-SH) in isolated homogenized whole brain samples. The results showed a significant reduction in SDL and prolongation of TL in the phosphamidon (1.74 mg/kg/d; p.o.) treated group at weeks 6 and 8 as compared to the control group. Two weeks treatment with PROG (15 mg/kg/d; i.p.) antagonized the effect of phosphamidon on SDL as well as TL. Phosphamidon alone produced a significant increase in the brain TBARS levels and decrease in the brain NP-SH levels. Treatment with PROG (15 mg/kg/d; i.p.) attenuated the effect of phosphamidon on oxidative stress. Together, the results showed that progesterone attenuated the cognitive dysfunction and increased oxidative stress induced by phosphamidon in the brain.

Effect of phosphamidon on convulsive behavior and biochemical parameters: modulation by progesterone and 4'-chlorodiazepam in rats.

Phosphamidon (PHOS) has been shown to affect nervous system adversely. The present study was designed to explore the modulation of the effects of PHOS on convulsions by neurosteroids, progesterone (PROG), and 4'-chlorodiazepam (4'-CD), in both acute and chronic seizure models. In acute study, seizures were induced by either pentylenetetrazole (PTZ) injection or maximal electroshock seizures, while in the chronic study, kindling was induced by injecting PTZ (30 mg/kg, s.c.) on alternate days three times in a week. Oxidative stress was assessed in the brain by measuring the levels of malondialdehyde (MDA), acetylcholinesterase (AChE), and non-protein thiol (NP-SH). PROG and 4'-CD were able to modulate the PHOS-induced convulsions in acute PTZ convulsions as well as in chronic kindling model. However, they failed to reverse the derangements in oxidative stress parameters of MDA and NP-SH produced by PHOS in kindled animals. PROG significantly increased the AChE activity in untreated rats, while PROG and 4'-CD reversed the AChE activity inhibition induced by PHOS. The study indicates a possible anticonvulsive mechanism of neurosteroids, since both PROG and 4'-CD reversed PHOS-induced inhibition of AChE activity. The neurosteroids seem to play a protective role in PHOS-induced convulsions besides their antioxidant property.