A review of clinical studies involving pregnant women registered in the Clinical Trials Registry of India.

CONTEXT AND AIMS: Pregnant women undergo physiological changes which influence the efficacy as well as safety of medications used. Very few drugs are tested and approved for medical conditions during pregnancy, and less pharmacokinetic data are available to form clinical treatment guidelines. There was no data available regarding the type of research studies conducted in pregnancy in India. Hence, we conducted this study to analyze the type of research studies in pregnancy registered in the Clinical Trials Registry of India (CTRI). SUBJECTS AND METHODS: Following exemption from review by the Institutional Ethics Committee, all studies in pregnant women registered in CTRI from its inception in July 2007 to June 2018 were reviewed. Data were captured with respect to geographical distribution, trimester of pregnancy, study designs used, therapy area, and funding. STATISTICAL ANALYSIS USED: The variables were analyzed using descriptive statistics using SPSS version 16.0. RESULTS: Out of a total of 14,911 studies in CTRI, a total of 285 (1.91%) studies involved pregnant women. Of these studies, 199 (69.8%) were interventional, whereas 86 (30.1%) were observational. Of all the interventional studies, 119 (60%) tested drugs, 47 (24%) tested a nondrug intervention, and the rest were nutraceuticals, Ayurveda, Yoga and Naturopathy, Unani, Siddha, and Homeopathy, and vaccines. Postgraduate theses constituted 140 (49.1%) studies, 79 (27.7%) were academic projects, 27 (9.4%) were government-funded studies, and only 16 (5.6%) were pharmaceutical-sponsored studies. The most commonly studied therapy area was anesthesia, followed by hypertension and induction of labor. CONCLUSIONS: This study depicts underrepresentation of pregnant women in clinical studies and more evidence needs to be generated with respect to drug safety and pharmacokinetics.

Effect of montelukast in experimental model of Parkinson's disease.

Despite the availability of many drugs offering symptomatic relief in Parkinson's disease, there are no drugs available offering neuroprotective effect. Hence, it was decided to evaluate the neuroprotective effect of montelukast, an anti-inflammatory drug, in rotenone induced model of Parkinson's disease in rats. Forty eight male wistar rats were randomly divided into three groups. Group 1: Vehicle control, Group 2: Montelukast 5 mg/kg, Group 3: Montelukast 10 mg/kg. All the groups received rotenone 2.5 mg/kg intraperitoneally for 10 days as a disease inducing agent. The study drug montelukast was administered to respective groups orally from day 11 to day 24. On day 25, 24 h after 14 days of study drug administration, the rats were subjected to open field test, rota rod test and catalepsy test. Brain samples of rats from each group were collected for Malondialdehyde(MDA), Glutathione(GSH) and TNFα analysis. In the open field test both the doses of montelukast showed significant increase in the locomotor activity and also decreased the immobility time compared to vehicle (p < 0.05). In rotarod test, montelukast 5 mg/kg and 10 mg/kg showed significant increase in the time to fall, compared to vehicle (p < 0.05). In catalepsy test, both doses of montelukast significantly decreased the retraction time compared to vehicle(p < 0.05). The brain MDA levels were decreased and GSH levels were found to be higher in the two montelukast groups compared to vehicle (p < 0.05). TNFα levels too were decreased significantly on montelukast administration. Montelukast showed potential neuroprotective effect by virtue of its anti-oxidant and anti-inflammatory actions.

Current Status of Delamanid in the Management of MDR Tuberculosis.

Delamanid is a nitro-dihydro-imidazooxazole compound which was developed by a Japanese company, Otsuka Holdings inc. and has shown in-vitro and in-vivo activity against drug resistant tuberculosis. The drug exerts its anti-mycobacterial activity by inhibition of mycolic acid biosynthesis, leading to defective cell wall formation ultimately leading to bacterial death. Following the promising results in Phase 2 trials, Delamanid received approval in European Union in 2014, following which it was also approved in Japan and Korea in the same year. It was approved in India recently in August, 2017. Though relatively well tolerated, there have been concerns due to QT prolongation associated with the use of Delamanid. WHO has currently recommended use of Delamanid in combination with optimized background regimen in patients with pulmonary TB (conditional recommendation). More data from clinical trials and observational studies is awaited regarding use of Delamanid in children, HIV co-infection, pregnant women and use in combination with Bedaquiline.

Drug Utilization in Neonatal Intensive Care Unit of a Tertiary-care Hospital in Mumbai, India.

OBJECTIVE: To study the prescription pattern (using applicable WHO indicators), cost analysis and off-label use of drugs in neonatal intensive care unit (NICU) of a tertiary-care hospital. METHODS: The prescriptions of 460 neonates admitted to a NICU during July 2014-March 2015 were studied prospectively. RESULTS: Of 460 neonates, 54.8% were preterm and 73% were low birth weight (LBW). The mean (SD) prescription items per neonate were 5.7 (3.6). Overall off-label use was 12.3%, while 38% neonates received at least one off-label drug. Of 326 off-label drugs, antibiotics (69.6%) followed by non-steroid anti-inflammatory drugs (7%) were commonly used. Premature and LBW babies required more drugs with higher cost and longer stay, compared to full term and normal weight babies (P<0.01), while the pattern of off-label use was similar across both these categories (P>0.05). CONCLUSION: Off-label antibiotics use was common, and prescribing practices were uniform in NICU.