M. Vishaal Varma

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To develop physiologically based pharmacokinetic (PBPK) model to predict the pharmacokinetics and drug-drug interactions (DDI) of pravastatin, using the in vitro transport parameters. In vitro hepatic sinusoidal active uptake, passive diffusion and canalicular efflux intrinsic clearance values were determined using sandwich-culture human hepatocytes (SCHH)(More)
Drug efflux pumps like P-glycoprotein (P-gp) and multidrug resistance (MDR) proteins were recognized to possess functional role in determining the pharmacokinetics of drugs administered by peroral as well as parenteral route. Advancements in molecular biology, to some extent, had revealed the structure, localization and functional role of P-glycoprotein and(More)
Oral bioavailability (F) is a product of fraction absorbed (Fa), fraction escaping gut-wall elimination (Fg), and fraction escaping hepatic elimination (Fh). In this study, using a database comprised of Fa, Fg, Fh, and F values for 309 drugs in humans, an analysis of the interrelation of physicochemical properties and the individual parameters was carried(More)
The present investigation attempts to increase intestinal permeability and hence absorption of biopharmaceutic classification system (BCS) Class III (cefotaxime sodium (CX)) and Class IV (cyclosporin A (CSA)) drugs by employing certain absorption enhancers. Drugs were co-perfused with sodium caprate (SC, 0.25% w/v), piperine (P, 0.004% w/v) and sodium(More)
The Biopharmaceutics Classification System (BCS) is a scientific framework that provides a basis for predicting the oral absorption of drugs. These concepts have been extended in the Biopharmaceutics Drug Disposition Classification System (BDDCS) to explain the potential mechanism of drug clearance and understand the effects of uptake and efflux(More)
Prediction of human pharmacokinetics of new drugs, as well as other disposition attributes, has become a routine practice in drug research and development. Prior to the 1990s, drug disposition science was used in a mostly descriptive manner in the drug development phase. With the advent of in vitro methods and availability of human-derived reagents for in(More)
Hepatobiliary transport mechanisms have been identified to play a significant role in determining the systemic clearance for a number of widely prescribed drugs and an increasing number of new molecular entities (NMEs). While determining the pharmacokinetics, drug transporters also regulate the target tissue exposure and play a key role in regulating the(More)
Glucokinase is a key regulator of glucose homeostasis, and small molecule allosteric activators of this enzyme represent a promising opportunity for the treatment of type 2 diabetes. Systemically acting glucokinase activators (liver and pancreas) have been reported to be efficacious but in many cases present hypoglycaemia risk due to activation of the(More)
The aim of the present study is to evaluate the quantitative contribution of passive permeability to P-glycoprotein-mediated (P-gp-mediated) efflux and the functional activity of P-gp in determining intestinal absorption of drugs, and demonstrate the relationship between efflux parameters and intestinal permeability. MDRI-MDCKII cell monolayer permeability,(More)
Solubility and permeability being important determinants of oral drug absorption, this study was aimed to investigate the effect of D-alpha-tocopheryl polyethylene glycol 1000 succinate (TPGS) on the solubility and intestinal permeability of paclitaxel in vitro, in situ and in vivo, in order to estimate the absorption enhancement ability of TPGS. Aqueous(More)