A series of exploratory investigations with multiple agents was carried out in normal rats and in rats with uranyl nitrate-induced acute renal failure to understand the disposition characteristics of intravenous topotecan (TPT) used as a model substrate. The disposition of TPT was unaltered in normal rats when treated with methotrexate, whereas treatment with probenecid increased the systemic exposure of TPT. In case of uranyl nitrate-induced acute renal failure (UN-ARF) rats, the systemic exposure of TPT was increased when compared with normal rats, whereas in UN-ARF rats treated with probenecid a further reduction in renal clearance of TPT was noted as compared with that of UN-ARF induced rats. Thus, TPT may be involved in the tubular secretory pathway when a passive glomerular filtration pathway for elimination was not possible. The disposition of TPT did not normalize in UN-ARF rats when treated with caffeine, a non-selective adenosine A1 receptor antagonist, whereas the selective adenosine A1 receptor antagonist (1,3-dipropyl-8-phenylxanthine, DPPX) normalized TPT pharmacokinetic disposition by improving renal function. Renal excretion studies demonstrated that CLR improved by almost fivefold following DPPX treatment in ARF rats. In addition, the qualitative stability/metabolism pattern of TPT in liver microsomes prepared from various groups of rats (normal rats, UN-ARF rats, rats treated with DPPX, and UN-ARF rats treated with DPPX) was found to be similar. In summary, using a pharmacokinetic tool as a surrogate, it has been shown that the pharmacokinetic disposition of TPT improved considerably upon treatment with DPPX, a selective adenosine A1 antagonist.

Diabetes mellitus (DM) prevalence is increasing at an alarming rate as it was 381 million people globally in 2013 and is estimated to be 463 million people in 2019 rising to 578 million by 2030. It is a disease with high rate of complications such as neuropathy, nephropathy, retinopathy, erectile dysfunction etc. 1,2 Diabetic neuropathy is a family of disorders that damage the different regions of the nervous system, either individually or in combination. It affects pain fibres, motor neurons and autonomic nervous system. 3 It results in large economic costs for its care. [4][5][6] The various kind of neuropathies include peripheral neuropathy, proximal neuropathy, autonomic neuropathy and focal neuropathy. 7 There are a number of reasons for the pathogenesis of diabetic neuropathy and polyol pathway of glucose metabolism is thought as one of the major mechanism. 8 Peripheral neuropathy is a type of nerve damage that usually affects feet and legs and sometimes hands and arms. 9 It is proved that reactive oxygen species (ROS) plays a significant role in the pathophysiology of neuropathic pain in diabetes. 10 Out of all diabetic patients, 50% of patients develop neuropathy and painful neuropathy ranges from 10% to 20% in patients with diabetes. Diabetic patients can experience nerve problems at any time and the problem increases with age, weight and duration. 5 The complications across various countries varies from 10% to 30% and it is higher in developed countries than in developing countries. These complications can lead to painful symptoms and can affect quality of life of the patient. The treatment for the painful diabetic

A simple and sensitive method for the determination of methylene chloride as residual solvent was developed and validated on gas liquid chromatograph fitted with flame ionization detector. The carrier gas was nitrogen, and separation was carried out on BP 5 capillary column consisting of 5% phenyl and 95% dimethyl polysiloxane stationary phase. The retention time for methylene chloride was 5.4 min. The method was extended for determination of the methylene chloride organic volatile impurity in the marketed formulations of ciprofloxacin hydrochloride, norfloxacin, pefloxacin and ofloxacin.