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Effects of Liver Impairment on the Pharmacokinetics of Brivanib, a Dual Inhibitor of Fibroblast Growth Factor Receptor and Vascular Endothelial Growth Factor Receptor Tyrosine Kinases
(StemScientific, 2000) Syed, Shariq
Background: Many patients with hepatocellular carcinoma (HCC) have liver impairment as a result of tumor burden and cirrhosis. Brivanib, which is administered orally as the prodrug brivanib alaninate, is a selective, dual inhibitor of fibroblast growth factor receptor and vascular endothelial growth factor receptor tyrosine kinases that is currently in phase III studies for HCC. Methods: This phase I study compared the pharmacokinetic profile of brivanib in patients with HCC and varying levels of hepatic impairment with that of patients with advanced solid non-HCC malignancies and normal hepatic function. Patients were assigned to 1 of 4 study groups: Group A, HCC plus Child-Pugh (CP) A status (mild hepatic impairment); Group B, HCC plus CP B (moderate hepatic impairment); Group C, HCC plus CP C (severe hepatic impairment); and Group D, non-HCC malignancy and normal hepatic function. Plasma brivanib concentrations were determined on Days 1 and 28. Brivanib alaninate doses were 400 mg/day in Groups A, B, and D, and 200 mg/day in Group C. Results: Of the 52 enrolled patients, 24 were assigned to 1 of the 4 groups (6 patients/group). After a single brivanib alaninate dose, the brivanib maximum observed plasma concentration and the area under the concentration-time curve from time zero extrapolated to infinity (AUCinf) in patients with HCC and mild or moderate hepatic impairment (Groups A and B) were comparable with those in patients with normal hepatic function (Group D). Brivanib AUCinf was approximately 50% higher in patients with HCC and severe hepatic impairment (Group C) compared with patients with normal hepatic function (Group D). Brivanib alaninate 400 mg/day was tolerated in Groups A, B, and D. Tolerability could not be assessed in Group C because of dose interruptions and discontinuations. Based on modified World Health Organization criteria, stable disease was achieved in 8 of 18 patients (44.4%) with HCC and 1 of 6 patients (17%) with non-HCC tumors. Conclusions: Brivanib exposure in patients with HCC and mild or moderate hepatic impairment was similar to that in patients with non-HCC malignancies and normal hepatic function, suggesting that dose adjustment is not necessary in HCC patients with CP A and B status. Experience in patients with HCC and CP C status is insufficient to recommend brivanib use in this population.
Multiple Dose Pharmacokinetics of Caffeine Administered in Chewing Gum to Normal Healthy Volunteers
(BIOPHARMACEUTICS & DRUG DISPOSITION, 2005) Syed, Shariq
The purpose of this study was to examine the pharmacokinetics of three doses of caffeine administered as Stay Alert1 chewing gum in a multiple dose regimen. Methods: A double-blind, parallel randomized, four-treatment study design was employed. The treatment groups were: 50, 100 and 200mg caffeine and placebo. Subjects were 48 (n ¼ 12 per group), healthy, non-smoking, males and females who had abstained from caffeine ingestion for at least 20 h prior to dosing, who were randomly assigned to the treatment groups. Caffeine was administered at 2400, 0200 and 0400 h depending on the treatment group. Blood samples were collected pre-dose and at 5, 15, 30, 45, 60, 75, 90 and 105 min after each caffeine dose. Samples were also collected at 7.5, 8.5 and 18 h after the last dose of caffeine. Plasma caffeine levels were analysed by a validated UV-HPLC method. Result: The mean Tmax after the third dosing ranged from 0.37 to 1.12 h. Cmax for 50, 100 and 200mg was 2.69, 3.45 and 6.33 mg/l, respectively. AUCinf for 50, 100 and 200mg group was 33.2, 46.94 and 86:94 mg=l h, respectively. AUCinf values suggested a dose proportionate increase. Dose normalized Cmax and AUC0 t values across doses were not significantly different, suggesting linearity was maintained after multiple doses of the Stay Alert1 chewing gum. There were no group related differences in elimination. Conclusions: The results suggest that caffeine administered in the gum formulation (Stay Alert1 chewing gum) via a multiple dosing regimen provides an effective and convenient means of maintaining effective concentrations of caffeine that would in some operational scenarios be desirable for maintaining alertness and performance in sleep deprived individuals. Copyright # 2005 John Wiley & Sons, Ltd. Key words: caffeine chewing gum; caffeine multiple dose; pharmacokinetics; buccal absorption
Transport, Metabolism, and in Vivo Population Pharmacokinetics of the Chloro Benztropine Analogs, a Class of Compounds Extensively Evaluated in Animal Models of Drug Abuse
(THE JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS, 2007) Syed, Shariq
Recently, extensive behavioral research has been conducted on the benztropine (BZT) analogs with the goal of developing successful therapeutics for cocaine abuse. The present study was conducted to characterize the contribution of dispositional factors in mediating the behavioral differences among the chloro BZT analogs and to identify cytochrome P450 enzymes involved in their metabolism. Bidirectional transport and efflux studies of four of the chloro BZT analogs were conducted. Screening with a panel of human and rat Supersomes was performed for 4 ,4 -diCl BZT. In addition, pharmacokinetic and brain distribution studies for 4 -Cl and 4 ,4 -diCl BZT in Sprague-Dawley rats were conducted. The permeability of the chloro analogs ranged from 8.26 to 32.23 and from 1.37 to 21.65 10 6 cm/s, whereas the efflux ratios ranged from 2.1 to 6.9 and from 3.3 to 28.4 across Madin-Darby canine kidneymultidrug resistance 1 (MDCK-MDR1) and Caco-2 monolayers, respectively. The P-glycoprotein (P-gp) inhibitor verapamil reduced the efflux ratios and enhanced the absorptive transport of the chloro BZT analogs. 4 ,4 -diCl BZT was a substrate of human CYP2D6 and 2C19 and rat 2C11 and 3A1. The brain uptake for 4 -Cl and 4 ,4 -diCl BZT was comparable and higher than previously reported for cocaine (brain-to-plasma partition coefficient 4.6–4.7 versus 2.1 for cocaine). The rank order for t1/2 was 4 ,4 -diCl BZT 4 -Cl BZT cocaine and for steadystate volume of distribution was 4 -Cl BZT 4 ,4 -diCl BZT cocaine. In conclusion, the chloro analogs differ significantly in their clearance and duration of action, which correlates to their behavioral profiles and abuse liability. Furthermore, these results suggest that the distinctive behavioral profile of these analogs is not due to limited brain exposure.
Population Pharmacokinetics, Brain Distribution, and Pharmacodynamics of 2nd Generation Dopamine Transporter Selective Benztropine Analogs Developed as Potential Substitute Therapeutics for Treatment of Cocaine Abuse
(JOURNAL OF PHARMACEUTICAL SCIENCES, VOL. 97, NO. 5, MAY 2008, 2008-05) Syed, Shariq
A second generation of N-substituted 3a-[bis(40-fluorophenyl)methoxy]- tropanes (GA 1–69, JHW 005 and JHW 013) binds with high affinity to the dopamine transporter (DAT) and are highly selective toward DAT compared to muscarinic receptor binding (M1). The objective of this study was to characterize brain distribution, pharmacokinetics, and pharmacodynamics [extracellular brain dopamine (DA) levels] of three novel N-substituted benztropine (BZT) analogs in male Sprague–Dawley rats. The BZT analogs displayed a higher distribution (Vd¼8.69–34.3 vs. 0.9 L/kg) along with longer elimination (t1/2: 4.1–5.4 vs. 0.5 h) than previously reported for cocaine. Brain-toplasma partition coefficients were 1.3–2.5 vs. 2.1 for cocaine. The effect of the BZT analogs on extracellular brain (DA) levels ranged from minimal effects (GA 1–69) to several fold elevation ( 850% of basal DA for JHW 013) at the highest dose evaluated. PK/PD analysis of exposure–response data resulted in lower IC50 values for the BZT analogs compared to cocaine indicating their higher potency to inhibit DA reuptake (0.1–0.3 vs. 0.7 mg/L). These BZT analogs possess significantly different PK and PD profiles as compared to cocaine suggesting that further evaluation as cocaine abuse therapeutics is warranted. 2007 Wiley-Liss, Inc. and the American Pharmacists Keywords: pharmacokinetics; pharmacodynamics; dopamine; benztropine analogs; cocaine.
Petrography and geochemistry of magnesite and talc deposits of Jhiroli, Kumaun Lesser Himalaya
(Magmatism, Tectonism And Mineralization: Macmillan Publishers India Ltd, 2009) Joshi, Prabha
The Veitsch type magnesite mineralization in association with talc from Jhiroli is confined within the stromatolitic dolomite of Deoban Formation. The dolomite represents many microlithotypes and characterized by nodules and bands of chert. Microtextures suggest a tidal flat environment where different phases of replacement of dolomite by magnesite were observed. Grain boundary relations, replacement features and different phases of reactions between magnesite and silica explain development of talc in the system. There is a noteworthy similarity in geochemical signatures of dolomite, magnesite and talc except a few major and minor elements, which suggest an external chemical flux is not responsible for the magnesite and talc mineralizations. On the basis of field relation, petrography and geochemistry it can be inferred that the marine, sparry magnesite deposits are product of diagenetic replacement of early dolomite in a protected intertidal carbonate flat environment whereas the associated talc deposits resulted from incipient/low grade regional burial metamorphism of these siliceous, magnesium bearing carbonates.
Role of fluids in the formation of talc deposits of Rema area, Kumaun Lesser Himalaya
(Springer, 2009-02) Joshi, Prabha
Talc deposits of Rema area in the Kumaun Inner Lesser Himalaya are hosted within high magnesium carbonates of the Proterozoic Deoban Formation. These deposits occur as irregular patches or pockets mainly within magnesite bodies, along with impurities of magnesite, dolomite and clinochlore. Textures represent different phases of reactions between magnesite and silica to produce talc. Petrography, XRD and geochemistry reveal that the talc has primarily developed at the expense of magnesite and silica, leaving dolomite largely un-reacted. Early fluid inclusions in magnesite and dolomite associated with talc are filled with H2O+NaCl+KCl ± MgCl2 ± CaCl2 fluids, which represent basin fluid system during diagenesis of carbonates. Their varied degree of re-equilibration was although not pervasive but points to increased burial, and hence requires careful interpretation. H2O-CO2 fluid with XCO2 between 0.06 and 0.12 was equilibrated with talc formation. The reaction dolomite+quartz → talc was not extensive because T-XCO2 was not favourable, and talc was developed principally after magnesite+quartz. Keywords Talc Fluid Inclusions Re-equilibration Kumaun Lesser Himalaya
Investigation on the characteristic properties of high performance SCC with mineral admixtures
(Indian Concrete Journal, 2009-09) Patil, Dada S.
In this experimental work, a mix design for self-compacting concrete has been carried out using Nan-Su method. Flow properties such as passing ability, filling ability, and segregation resistance were evaluated by varing the dosage of super plasticier (HRWRA) and viscoity modifing admixture.
Learning from the Past Intrusion Attacks: Digital Evidence Collection to Make e-Commerce Systems More Secure
(Conference ICL2009, 2009-09) Lokhande, P. S.
Use of computers, data communication and data storage devices has become so ubiquitous that most of the crimes or civil disputes have involvement in some way. There will be a large demand for computer forensics in the coming days. Computer forensic has four phases: Collection, Presentation, Filtering and presentation. Computer Forensic: It is an art and science of applying computer science to aid the legal process. Computer involvement in crime such as fraud, child pornography and threatening emails. Another situation where computers commonly assist in a crime is intellectual property theft in the corporate environment. Computers were the targets of the crime such as during a Denial of Service (DoS) attack against an E-Commerce site. It is often less obvious than previous cases. Computer contains information that is incidental to the crime such as a database containing the payment and receipts list of gamblers, drug traffickers, and scammers. Pay and receipts (owe) are the documents made in spreadsheets to keep track of their customers and suppliers. In the same cases other innocent bystanders computers, WiFi networks may have hacked to send threatening mail for example mails sent by terrorist group before the bomb Blast in various cities of India.
Genetic issues of some of the non metallic minerals in lesser Himalaya
(Iranian Journal of Earth Sciences, 2010) Joshi, Prabha
A brief account of the representative and workable industrial minerals namely magnesite, talc and barite in Lesser Himalaya, is presented here emphasizing their genesis. Deposits of magnesite and talc are found associated with Neoproterozoic, plateform type, shelf-slope limestone-dolomite host rocks from inner Lesser Himalayan sequences. Field, textural, geochemical signatures and fluid inclusions trapped in dolomite and magnesite reveal within basin processes, in an increased burial- diagenetic environment responsible for formation of magnesite replacing dolomite. Talc is formed at the expense of magnesite and silica, and with limited dolomite involvement at transition conditions from diagenetic to metamorphism. Barite deposit is hosted within Neoproterozoic Nagthat quartzite rocks of outer genetic understanding.
Website evaluation of select industries: an evaluation
(CESER Publications, 2010) Ansari, Shaheen N.
Technology has expanded the range and ease of information access at the expense of personal contact. The implications for libraries are substantial: a need to more clearly identify groups of users and their different needs. One way of attempting to meet such needs, and one of the most important new elements in the electronic library environment, is the website. Simultaneously, the need for evaluation is felt very keenly in libraries. In times of rapid and profound societal and technological change, evaluation is essential to preserving the viability and the visibility of libraries. This article describes how top ranking Pharma Industries perform, show their information strength. Therefore, their websites are evaluated to indirectly know the emphasis on information. This study has outlined the major aims and methods of select Pharmaceutical Industries websites. It has explored the criteria by which library websites are evaluated and the measures used to assess those criteria. Generally for evaluating websites there are many criteria available in literature. However, certain special criteria depending on the nature of subject and type of organization were found out for evaluation.
Lack of Effect of Brivanib on the Pharmacokinetics of Midazolam, a CYP3A4 Substrate, Administered Intravenously and Orally in Healthy Participants
(Journal of Clinical Phramacology, Online 9 June 2011, 2011) Syed, Shariq
Brivanib alaninate is the orally available prodrug of brivanib, a dual inhibitor of fibroblast growth factor and vascular endothelial growth factor signaling pathways that is under therapeutic investigation for various malignancies. Brivanib alaninate inhibits CYP3A4 in vitro, and thus there is potential for drug-drug interaction with CYP3A4 substrates, such as midazolam. The present study evaluated pharmacokinetic parameters and safety/ tolerability upon coadministration of brivanib alaninate and midazolam. Healthy participants received intravenous (IV) or oral midazolam with and without oral brivanib alaninate. Blood samples for pharmacokinetic analysis were collected up to 12 hours after midazolam and up to 48 hours after brivanib alaninate. Twenty-four participants were administered study drugs; 21 completed the trial. No clinically relevant effect of brivanib alaninate on the overall exposure to midazolam following IV or oral administration was observed. Orally administered brivanib alaninate was generally well tolerated in the presence of IV or oral midazolam. The lack of a pharmacokinetic interaction between brivanib and midazolam indicates that brivanib alaninate does not influence either intestinal or hepatic CYP3A4 and confirms that brivanib alaninate may be safely coadministered with midazolam and other CYP3A4 substrates. Keywords: brivanib; midazolam; pharmacokinetics; VEGF inhibitor; FGF inhibitor
Phase I study to determine the safety, pharmacokinetics and pharmacodynamics of a dual VEGFR and FGFR inhibitor, brivanib, in patients with advanced or metastatic solid tumors
(Annals of Oncology, 2011) Syed, Shariq
Background: This study was designed to determine the safety, pharmacokinetics (PK) and pharmacodynamics (PD) of brivanib in patients with advanced/metastatic solid tumors. Patients and methods: Ninety patients enrolled in this two-part, phase I open-label study of oral brivanib alaninate. The primary objectives of this study were (in part A) dose-limiting toxicity, maximum tolerated dose (MTD) and the lowest biologically active dose level and (in part B) the optimal dose/dose range. The secondary objectives of this study were preliminary evidence of antitumor activity, PK and PD. Results: Across part A (open-label dose escalation and MTD) and part B (open-label dose optimization), 68 patients received brivanib alaninate. Brivanib demonstrated a manageable toxicity profile at doses of 180–800 mg. Most toxic effects were mild. Systemic exposure of the active moiety brivanib increased linearly £1000 mg/day. The MTD was 800 mg/day. Forty-four patients were treated at the MTD: 20 with 800 mg continuously, 11 with 800 mg intermittently and 13 with 400 mg b.i.d. doses. Partial responses were confirmed in two patients receiving brivanib ‡600 mg. Dynamic contrast-enhanced magnetic resonance imaging demonstrated statistically significant decreases in parameters reflecting tumor vascularity and permeability after multiple doses in the 800-mg continuous q.d. and 400-mg b.i.d. dose cohorts. Conclusion: In patients with advanced/metastatic cancer, brivanib demonstrates promising antiangiogenic and antitumor activity and manageable toxicity at doses £800 mg orally q.d., the recommended phase II study dose. Key words: antiangiogenesis, brivanib, fibroblast growth factor, vascular endothelial growth factor
Lack of food eVect on single-dose pharmacokinetics of brivanib, and safety and eYcacy following multiple doses in subjects with advanced or metastatic solid tumors
(Cancer Chemotherapy and Pharmacology, 2011) Syed, Shariq
Purpose Brivanib alaninate, an orally available prodrug of brivanib, is currently under evaluation for the treatment of several malignancies. This study aimed to (1) investigate eVects of a high-fat meal on single-dose pharmacokinetics of brivanib in subjects with advanced/metastatic solid tumors and (2) assess the safety and preliminary eYcacy of single and multiple doses of brivanib alaninate in this population. Methods A two-part study was conducted consisting of a single-dose phase (Part A) and a multiple-dose phase (Part B). In Part A, subjects received a single dose of brivanib alaninate (800 mg) either in a fasting state or following ingestion of a high-fat meal (approximately 951 kcal [15% protein, 33% carbohydrate, 52% fat]); serial blood samples were collected for pharmacokinetic analysis up to 48 h post-dosing. In Part B, subjects received brivanib alaninate (800 mg) once daily until discontinuation. Throughout both phases, subjects were evaluated for adverse events (AEs) and best clinical response. Results No clinically signiWcant diVerences in brivanib exposure were observed between fed and fasting subjects in Part A; Cmax was unchanged and AUCINF decreased marginally when administered in a fed versus fasted state. In Part A, the incidence of treatment-emergent AEs was broadly similar in a fed or fasted state. Brivanib alaninate was generally well tolerated throughout the study and showed preliminary evidence of antitumor activity. Conclusions Consumption of a high-fat meal had no signiWcant eVect on brivanib pharmacokinetics. The study further demonstrates the acceptable safety/tolerability proWle and antitumor potential of brivanib in patients with advanced malignancies. Keywords Pharmacokinetics · Exposure · Food · Safety · Brivanib alaninate · Solid tumors
Phase I dose-escalation study to determine the safety, pharmacokinetics and pharmacodynamics of brivanib alaninate in combination with full-dose cetuximab in patients with advanced gastrointestinal malignancies who have failed prior therapy
(British Journal of Cancer, 2011) Syed, Shariq
BACKGROUND: The objectives of this phase I study were to determine the safety, pharmacokinetics (PK), pharmacodynamics and efficacy of brivanib combined with full-dose cetuximab in patients with advanced gastrointestinal malignancies. METHODS: Patients with advanced gastrointestinal malignancies who had failed prior therapies received brivanib (320, 600 or 800 mg daily) plus cetuximab (400 mgm–2 loading dose then 250 mgm–2 weekly). Assessments included adverse events, PK, tumour response, 2[18F]fluoro-2-deoxyglucose positron-emitting tomography and K-Ras mutation analyses. RESULTS: Toxicities observed were manageable; the most common treatment-related toxicities (410% of patients) were fatigue, diarrhoea, anorexia, increase in aspartate aminotransferase and alanine aminotransferase, acneiform dermatitis, headache, mucosal inflammation, nausea, dry skin, vomiting, hypertension, pruritus, proteinuria and weight loss. Of 62 patients, 6 (9.7%) had objective radiographic partial responses, with an overall response rate of 10%. Median duration of response was 9.2 months; median progression-free survival was 3.9 months. CONCLUSIONS: The acceptable toxicity profile and efficacy of brivanib observed in this study were promising. These findings are being further evaluated in a phase III study of brivanib plus cetuximab vs cetuximab alone in patients previously treated with combination chemotherapy for K-Ras wild-type advanced metastatic colorectal cancer. Keywords: antiangiogenesis; brivanib; cetuximab; gastrointestinal tumours
Use of statistical methods in construction industry
(International Conference on Civil, Structural and Environmental Engineering: ICSEE, 2011-02-18) Parkar, Fauwaz
While manufacturing industry has generally been capable to apply new concepts successfully, construction industry still appears failing to apply them. Although these two industries differ significantly from each other, there is no obvious reason why construction industry should not be able to take advantage applying new concepts, and reject its denounced traditionalism. The new trends have been represented by concepts like mathematical modeling, operations research, lean production techniques, total quality management and just-in-time production. This paper is thus intended to highlight the various scenarios in the life-cycle of construction projects, where statistical methods can be used to overcome the drawbacks of traditional construction. Time studies have been conducted on various grades of manpower and equipments in Indian construction to measure their actual productivity. The application of statistical methods in construction provides construction managers and other decision makers the opportunity of experiencing and responding to various factors which are responsible for loss of productivity, and hence eliminating them.
Evaluation of curculigo orchioides mucilage as suspending agent
(International Journal of PharmTech Research, 2011-04) Gaikar, Nilesh
Plant products served as an alternative to synthetic products because of local accessibility, eco friendly nature and lower prices compared to imported synthetic products. The present study was undertaken to evaluate the mucilage obtained from the roots of Curculigo orchioides Gaertn. as a suspending agent. Characterization studies like solubility, swelling index, loss on drying, ash value, pH, viscosity along with microbial load and acute toxicity studies were carried out on the mucilage. Aluminium hydroxide gel suspension was prepared using different concentration of Curculigo orchioides mucilage and its properties were compared with standard suspending agents like sodium carboxymethylcellulose and Acacia. The evaluation parameters included the sedimentation profile, redispersability, rheology and particle size analysis. The results suggested that the mucilage was found to be a superior suspending agent than acacia indicating that it may be a good source as pharmaceutical adjuvant.
Lack of Effect of Brivanib on the Pharmacokinetics of Midazolam, a CYP3A4 Substrate, Administered Intravenously and Orally in Healthy Participants
(Sage Pubicaiton, 2011-06) Syed, Shariq
Brivanib alaninate is the orally available prodrug of brivanib, a dual inhibitor of fibroblast growth factor and vascular endothelial growth factor signaling pathways that is under therapeutic investigation for various malignancies. Brivanib alaninate inhibits CYP3A4 in vitro, and thus there is potential for drug-drug interaction with CYP3A4 substrates, such as midazolam. The present study evaluated pharmacokinetic parameters and safety/ tolerability upon coadministration of brivanib alaninate and midazolam. Healthy participants received intravenous (IV) or oral midazolam with and without oral brivanib alaninate. Blood samples for pharmacokinetic analysis were collected up to 12 hours after midazolam and up to 48 hours after brivanib alaninate. Twenty-four participants were administered study drugs; 21 completed the trial. No clinically relevant effect of brivanib alaninate on the overall exposure to midazolam following IV or oral administration was observed. Orally administered brivanib alaninate was generally well tolerated in the presence of IV or oral midazolam. The lack of a pharmacokinetic interaction between brivanib and midazolam indicates that brivanib alaninate does not influence either intestinal or hepatic CYP3A4 and confirms that brivanib alaninate may be safely coadministered with midazolam and other CYP3A4 substrates.
Luver as protagonist
(Domus India, 2011-11) Dalvi, Smita
Addressing the negotiation of the interior with the climate of the city. Bimal Patel and his multi-disciplinary team design the hardware for the skins of three building.
Architecture of new mosques in Kerala: appropriated aesthetics in the aftermath of urbanisaiton and globalisation
(International Conference on Islamic Art & Architecture (ICIAA), 2011-11) Dalvi, Smita
In recent times, the architectural features of the old mosques in Kerala, India are in the process of being replaced. traditional mosques were built in timber and like other religious structures in Kerala emerged from domestic traditions and evolved from local climate, materials, culture and traditions of craft....
Intermittent reservoir daily-inflow prediction using lumped and distributed data multi-linear regression models
(Indian Academy of Science, 2011-12) Magar, Rajendra
In this study, multi-linear regression (MLR) approach is used to construct intermittent reservoir daily inflow forecasting system. To illustrate the applicability and effect of using lumped and distributed input data in MLR approach, Koyna river watershed in Maharashtra, India is chosen as a case study. The results are also compared with autoregressive integrated moving average (ARIMA) models. MLR attempts to model the relationship between two or more independent variables over a dependent variable by fitting a linear regression equation. The main aim of the present study is to see the consequences of development and applicability of simple models, when sufficient data length is available. Out of 47 years of daily historical rainfall and reservoir inflow data, 33 years of data is used for building the model and 14 years of data is used for validating the model. Based on the observed daily rainfall and reservoir inflow, various types of time-series, cause-effect and combined models are developed using lumped and distributed input data. Model performance was evaluated using various performance criteria and it was found that as in the present case, of well correlated input data, both lumped and distributed MLR models perform equally well. For the present case study considered, both MLR and ARIMA models performed equally sound due to availability of large dataset.

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