Clinical Pharmacology

This laboratory offers therapeutic drug monitoring (TDM) services for voriconazole, posaconazole, imatinib, mycophenolate mofetil, and L-asparaginase. More than 4600 samples [Voriconazole (2194), Posaconazole (2410), MMF (17), L-asparaginase (44), and Imatinib (03), were reported for drug levels in 2023, benefitting more than 1000 patients undergoing treatment for leukemias, BMT and other indications.

The department has an active phase-1 unit to support pharmacokinetic, pharmacogenetic, BA/BE and first-in-human clinical trials. The 4- bed ward is a specialized unit capable of providing round the clock care and supervision to the study participants under the stewardship of an excellent team of study investigators, medical oncology and nursing staff.

The department is actively involved in developing therapeutic interventions for various cancers as well as the mitigation of serious adverse effects associated with cancer treatment. This includes development of radioprotectors and drugs for the prevention of morbidities associated with bone marrow transplantation such as graft versus host disease (GvHD). The pharmacokinetics and efficacy of drugs in special situations such as malnutrition are also being investigated. Efficacy of mitochondria-targeted drugs in therapy-resistant cancers is also being investigated. The lab undertakes end-to-end non-clinical investigations including pharmacokinetics and biodistribution, toxicity, efficacy and mechanistic studies.

Past Projects

• Bharat Pant , Jayant Goda , Vikram Gota.Drug development in LMICs: could the emerging Indian model usher the southeast Asian region? Lancet Reg Health Southeast Asia . 2024 Aug 16:29:100464.


• Rai A, Patwardhan RS, Jayakumar S, Pachpatil P, Das D, Panigrahi GC, Gota V, Patwardhan S, Sandur SK, et al.Clobetasol propionate, a Nrf-2 inhibitor, sensitizes human lung cancer cells to radiation-induced killing via mitochondrial ROS-dependent ferroptosis. Acta Pharmacol Sin . 2024 Jul;45(7):1506-1519. doi: 10.1038/s41401-024-01233-8. Epub 2024 Mar 13.


• Nikam SS, Vikram Gota, Gupta PC, Namrata Puntambekar, Singh A, Chaturvedi P, et al. Variability in addictive and carcinogenic potential of smokeless tobacco products marketed in Mumbai, India: a surveillance study. The Lancet Regional Health - Southeast Asia. 2024 Oct 1;29:100457–7.‌


• Garg, M., Gandhi, K., Gera, P., Jadhav, S. M., Mohanty, B., Gurjar, M., Sandupatla, B., Gala, R., Chaudhari, P., Prasad, M., Chinnaswamy, G., & Gota, V. (2024). Implications of chronic moderate protein-deficiency malnutrition on doxorubicin pharmacokinetics and cardiotoxicity in early post-weaning stage. Life sciences, 350, 122765.


• Gohil, D., Gandhi, K. A., Gupta, S. K., Gera, P., Yadav, S., Patwardhan, R., Checker, R., Sharma, D., Khattry, N., Sandur, S., & Gota, V. (2024). Immunomodulation by juglone alleviates acute graft-versus-host disease without compromising the graft-versus-leukaemia activity in mice. British Journal of Pharmacology, Online ahead of print.


• Batcha, J. S. D., Gota, V., Matcha, S., Raju, A. P., Rao, M., Udupa, K. S., & Mallayasamy, S. (2024). Predictive performance of population pharmacokinetic models of imatinib in chronic myeloid leukemia patients. Cancer Chemotherapy and Pharmacology, Online ahead of print.


• Sengupta, S., Biswas, M., Gandhi, K. A., Gupta, S. K., Gera, P. B., Gota, V., & Sonawane, A. (2024). Preclinical evaluation of engineered L-asparaginase variants to improve the treatment of Acute Lymphoblastic Leukemia. Translational Oncology, 43, 101909.


• Gupta, S. K., Gohil, D., Momin, M. B., Yadav, S., Chichra, A., Punatar, S., Gokarn, A., Mirgh, S., Jindal, N., Nayak, L., Hingorani, L., Khattry, N., & Gota, V. (2024). Withania Somnifera Extract Mitigates Experimental Acute Graft versus Host Disease Without Abrogating Graft Versus Leukemia Effect. Cell Transplantation, 33, 9636897241226573.


• Arun, B., Joshi, M., Kakkar, A. K., Madki, S., Ivaturi, V., Chinnaswamy, G., Banavali, S., & Gota, V. (2024). Bioequivalence study followed by model-informed dose optimization of a powder for oral suspension of 6-mercaptopurine. Pediatric Blood & Cancer, 71(3), e30813.


• Kumar, S., Castelino, R., Rao, A., Gattani, S., Kumar, A., Pillai, A., Sehgal, A., Rane, P., Ramaswamy, A., Dhekale, R., Krishnamurthy, J., Banavali, S., Badwe, R., Prabhash, K., Noronha, V., & Gota, V. (2024). Performance of potentially inappropriate medications assessment tools in older Indian patients with cancer. Cancer Medicine, 13(1), e6797.


• Garg, M., Gandhi, K., Jadhav, S. M., Gurjar, M., & Gota, V. (2023). Effect of Moderate Malnutrition on the Pharmacokinetics of Etoposide and Vincristine in Freshly Weaned Rats. European Journal of Drug Metabolism and Pharmacokinetics, 48(6), 657–663.


• Kumar Gupta, S., Gohil, D., Dutta, D., Panigrahi, G. C., Gupta, P., Dalvi, K., Khanka, T., Yadav, S., Kumar Kaushal, R., Chichra, A., Punatar, S., Gokarn, A., Mirgh, S., Jindal, N., Nayak, L., Tembhare, P. R., Hasan, S. K., Kumar Sandur, S., Hingorani, L., Khattry, N., & Gota, V. (2023). Withaferin-A alleviates acute graft versus host disease without compromising graft versus leukemia effect. International Immunopharmacology, 121, 110437.


• Gaur, T., Ali, A., Sharma, D., Gupta, S. K., Gota, V., Bagal, B., Platzbeckar, U., Mishra, R., Dutt, A., Khattry, N., Mills, K., Hasan, M. I., Sandur, S., & Hasan, S. K. (2024). Mitocurcumin utilizes oxidative stress to upregulate JNK/p38 signaling and overcomes Cytarabine resistance in acute myeloid leukemia. Cell Signal, 114, 111004.


• Patwardhan, R. S., Gohil, D., Singh, B., Kumar, B. K., Purohit, V., Thoh, M., Checker, R., Gardi, N., Gota, V., Kutala, V. K., Patwardhan, S., Sharma, D., & Sandur, S. K. (2024). Mitochondrial-targeted curcumin inhibits T-cell activation via Nrf2 and inhibits graft-versus-host-disease in a mouse model. Phytotherapy Research, 38(3), 1555–1573.


• Gupta, S. K., Jadhav, S., Gohil, D., Panigrahi, G. C., Kaushal, R. K., Gandhi, K., Patil, A., Chavan, P., & Gota, V. (2022). Safety, toxicity and pharmacokinetic assessment of oral Withaferin-A in mice. Toxicology Reports, 9, 1204–1212.


• Sengar, M., Jain, H., Shet, T., Sridhar, E., Gota, V., Rangarajan, V., Laskar, S. S., Alahari, A., Thorat, J., Agarwal, A., Sharma, N., Gupta, H., Kannan, S., Kumar, S., Nayak, L., Menon, H., Gujral, S., & Bagal, B. (2023). Phase II trial of a novel chemotherapy regimen CVEP (cyclophosphamide, vinblastine, etoposide and prednisolone) for acquired immunodeficiency syndrome (AIDS)-associated lymphomas. Br J Haematol, 200(4), 429-439. PMID: 36323643.


• Johnson, S., Dhamne, C., Sankaran, H., Gandhi, K. A., Rane, P., Moulik, N. R., Jadhav, S. M., Gurjar, M., Narula, G., Banavali, S., & Gota, V. (2022). A prospective, open-label, randomised, parallel design study of 4 generic formulations of intramuscular L-asparaginase in childhood precursor B-cell acute lymphoblastic leukaemia (ALL). Cancer Chemother Pharmacol, 90(6), 445-453. PMID: 36251032.


• Gohil, D., Panigrahi, G. C., Gupta, S. K., Gandhi, K. A., Gera, P., Chavan, P., Sharma, D., Sandur, S., & Gota, V. (2022). Acute and sub-acute oral toxicity assessment of 5-hydroxy-1,4-naphthoquinone in mice. Drug Chem Toxicol, 1-14. PMID: 35899689.


• Shriyan, B., Mehta, P., Patil, A., Jadhav, S., Kumar, S., Puri, A. S., Govalkar, R., Krishnamurthy, M. N., Punatar, S., Gokarn, A., Khattry, N., & Gota, V. (2022). Role of ADME gene polymorphisms on imatinib disposition: results from a population pharmacokinetic study in chronic myeloid leukaemia. Eur J Clin Pharmacol, 78(8), 1321-1330. PMID: 35652931.


• Gandhi, K. A., Joshi, A., Mehta, P., Gurjar, M., Rane, P., Sharma, J., Patil, A., Nookala, M., Noronha, V., Prabhash, K., & Gota, V. (2022). Feasibility of therapeutic drug monitoring of sunitinib and its implications on response and toxicity in patients with metastatic renal cell cancer. Cancer Chemother Pharmacol, 89(6), 751-759. PMID: 35441269.


• Punatar, S., Katti, K., Rajamanickam, D., Patil, P., Dhakan, C., Bagal, B., Gokarn, A., Bonda, A., Nayak, L., Gurjar, M., Kannan, S., Chiplunkar, S., Gota, V., & Khattry, N. (2022). Role of Curcumin in Reducing Toxicities Associated With Mucosal Injury Following Melphalan-Based Conditioning in Autologous Transplant Setting. Cell Transplant, 31, 9636897221086969. PMID: 35435039.


• Ostwal, V., Ramaswamy, A., Gota, V., Bhargava, P. G., Srinivas, S., Shriyan, B., Jadhav, S., Goel, M., Patkar, S., Mandavkar, S., Naughane, D., Daddi, A., Nashikkar, C., Shetty, N., Ankathi, S. K., & Banavali, S. D. (2022). Phase I Study Evaluating Dose De-escalation of Sorafenib with Metformin and Atorvastatin in Hepatocellular Carcinoma (SMASH). Oncologist, 27(3), 165-e222. PMID: 35274724.


• Nikam, S. S., Gurjar, M., Singhavi, H., Patil, A., Singh, A., Villalta, P., Chaturvedi, P., Khariwala, S. S., Gota, V., & Stepanov, I. (2021). Simultaneous analysis of urinary total 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol, N'-nitrosonornicotine, and cotinine by liquid chromatography-tandem mass-spectrometry. Sci Rep, 11(1), 20007. PMID: 34625573.


• Gandhi, V. V., Gandhi, K. A., Kumbhare, L. B., Goda, J. S., Gota, V., & Priyadarsini, K. I., Kunwar, A. (2021). 3,3'-Diselenodipropionic acid (DSePA) induces reductive stress in A549 cells triggering p53-independent apoptosis: A novel mechanism for diselenides. Free Radic Biol Med, 175, 1-17. PMID: 34425189.


• Patil, A., Shriyan, B., Mehta, P., Patil, M., Gurjar, M., Nookala, M., Patil, V., Joshi, A., Noronha, V., Prabhash, K., & Gota, V. (2021). ADME gene polymorphisms do not influence the pharmacokinetics of docetaxel: Results from a population pharmacokinetic study in Indian cancer patients. Cancer Med, 10(14), 4948-4956. PMID: 34156160.


• Chaudhary, N., Choudhary, B. S., Shah, S. G., Khapare, N., Dwivedi, N., Gaikwad, A., Joshi, N., Raichanna, J., Basu, S., Gurjar, M., P K S, Saklani, A., Gera, P., Ramadwar, M., Patil, P., Thorat, R., Gota, V., Dhar, S. K., Gupta, S., & Das, M., Dalal, S. N. (2021). Lipocalin 2 expression promotes tumor progression and therapy resistance by inhibiting ferroptosis in colorectal cancer. Int J Cancer, 149(7), 1495-1511. PMID: 34146401.


• Gota, V., Nookala, M., Bonda, A., Karanam, A., Shriyan, B., Kembhavi, Y., Gurjar, M., Patil, A., Singh, A., Goyal, N., Gupta, S. (2021). Effect of body mass index on pharmacokinetics of paclitaxel in patients with early breast cancer. Cancer Med, 10(9), 3068-3076. PMID: 33826243.


• Sharma, J. B., Krishnamurthy, M. N., Awase, A., Joshi, A., Patil, V., Noronha, V., Prabhash, K., & Gota, V. (2021). Validation of a novel causality assessment scale for adverse events in non-small cell lung carcinoma patients treated with platinum and pemetrexed doublet chemotherapy. Ther Adv Drug Saf, 12, 2042098621991280. PMID: 33628419.


• Nookala Krishnamurthy, M., Narula, G., Gandhi, K., Awase, A., Pandit, R., Raut, S., Singh, R., Gota, V., & Banavali, S. D. (2020). Randomized, Parallel Group, Open-Label Bioequivalence Trial of Intramuscular Pegaspargase in Patients With Relapsed Acute Lymphoblastic Leukemia. JCO Glob Oncol, 6, 1009-1016. PMID: 32628582.


• Shriyan, B., Patil, D., Gurjar, M., Nookala, M., Patil, A., Kannan, S., Patil, V., Joshi, A., Noronha, V., Prabhash, K., & Gota, V. (2020). Safety and CSF distribution of high-dose erlotinib and gefitinib in patients of non-small cell lung cancer (NSCLC) with brain metastases. Eur J Clin Pharmacol, 76(10), 1427-1436. PMID: 32529316.


• Gota, V., Purohit, V., Gurjar, M., Nayak, L., Punatar, S., Gokarn, A., Bonda, A., Bagal, B., Vora, C. S., Patil, A., Nookala, M., & Khattry, N. (2020). A Limited Sampling Strategy for Therapeutic Drug Monitoring of Mycophenolate Mofetil for Prophylaxis of Acute Graft-Versus-Host Disease in Allogeneic Stem Cell Transplantation. Cell Transplant, 29, 963689720912925. PMID: 32495641.


• Mehta, M., Gohil, D., Khattry, N., Kumar, R., Sandur, S., Sharma, D., Checker, R., Agarwal, B., Jha, D., Majumdar, A., & Gota, V. (2020). Prevention of acute graft-versus-host-disease by Withaferin a via suppression of AKT/mTOR pathway. Int Immunopharmacol, 84, 106575. PMID: 32416453.


• Bandekar, M., Maurya, D. K., Sharma, D., Checker, R., Gota, V., Mishra, N., & Sandur, S. K. (2020). Xenogeneic transplantation of human WJ-MSCs rescues mice from acute radiation syndrome via Nrf-2-dependent regeneration of damaged tissues. Am J Transplant, 20(8), 2044-2057. PMID: 32040239.


• Sankaran, H., Sengupta, S., Purohit, V., Kotagere, A., Moulik, N. R., Prasad, M., Dhamne, C., Narula, G., & Banavali, S., & Gota, V. (2020). A comparison of asparaginase activity in generic formulations of E.coli derived L- asparaginase: In-vitro study and retrospective analysis of asparaginase monitoring in pediatric patients with leukemia. Br J Clin Pharmacol, 86(6), 1081-1088. PMID: 31925802.


• Kothekar, A. T., Divatia, J. V., Myatra, S. N., Patil, A., Nookala Krishnamurthy, M., Maheshwarappa, H. M., Siddiqui, S. S., Gurjar, M., Biswas, S., & Gota, V. (2020). Clinical pharmacokinetics of 3-h extended infusion of meropenem in adult patients with severe sepsis and septic shock: implications for empirical therapy against Gram-negative bacteria. Ann Intensive Care, 10(1), 4. PMID: 31925610.


• Patil, V. M., Noronha, V., Joshi, A., Dhumal, S., Mahimkar, M., Bhattacharjee, A., Gota, V., Pandey, M., Menon, N., Mahajan, A., Sable, N., Kumar, S., Nawale, K., Mukadam, S., Solanki, B., Das, S., Simha, V., Abraham, G., Chandrasekharan, A., Talreja, V., DSouza, H., Srinivas, S., Kashyap, L., & Banavali, S. (2019). Phase I/II Study of Palliative Triple Metronomic Chemotherapy in Platinum-Refractory/Early-Failure Oral Cancer. J Clin Oncol, 37(32), 3032-3041. PMID: 31539316.


• Gandhi, K. A., Goda, J. S., Gandhi, V. V., Sadanpurwala, A., Jain, V. K., Joshi, K., Epari, S., Rane, S., Mohanty, B., Chaudhari, P., Kembhavi, S., Kunwar, A., Gota, V., & Priyadarsini, K. I. (2019). Oral administration of 3,3'-diselenodipropionic acid prevents thoracic radiation induced pneumonitis in mice by suppressing NF-kB/IL-17/G-CSF/neutrophil axis. Free Radic Biol Med, 145, 8-19. PMID: 31521664.


• Pires, N., Gota, V., Gulia, A., Hingorani, L., Agarwal, M., & Puri, A. (2019). Safety and pharmacokinetics of Withaferin-A in advanced stage high grade osteosarcoma: A phase I trial. J Ayurveda Integr Med, 11(1), 68-72. PMID: 30904387.



Patents

• Joshi M. R., Kakkar A. K., Gota V. P., Banavali S. D., Chinnaswamy G., Mandapati R. R., Shaik M. B. (2023). Oral Liquid Pharmaceutical Compositions of Isotretinoin. Patent Application No. 20230270707.


• Sharma D., Sandur S. K., Gota V. P., Patwardhan R. S., Singh B., Checker R., Maurya D. K., Joshi M., Giri A., Madki S., Gupta S. (2022). Chlorophyllin Containing Pharmaceutical Composition For Prevention Of Pathogenesis Of Coronavirus Disease. Patent Application No. 20220305023.


• Sharma D., Sandur S. K., Checker R., Patwardhan R. S., Gota V. P., Sundarraj J., Sasi P., Chattopadhyay S. (2019). Method of Adjuvant Treatment with Chlorophyllin Containing Therapeutic Preparation Including for Radioprotection of Normal Tissues During Radiation Therapy and Kit Therefor. Patent No. 10183026.


• Sharma D., Sandur S. K., Checker R., Patwardhan R. S., Gota V. P., Sundarraj J., Sasi P., Chattopadhyay S. (2017). Method of Adjuvant Treatment with Chlorophyllin Containing Therapeutic Preparation Including for Radioprotection of Normal Tissues During Radiation Therapy and Kit Therefor. Patent Application No. 20170290843.

Clinical Pharmacology,
Advanced Centre for Treatment, Research and Education in Cancer (ACTREC),
Tata Memorial Centre,
Plot No. 1& 2, Sector 22,KS-102/KS-150,
Kharghar, Navi Mumbai, Maharashtra 410210.
Telephone: 022 2740 5000 Extn.: 5470
Email: bioanalytical@actrec.gov.in