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Biomedical subjects

N A Kshirsagar

Publications and source records attributed to N A Kshirsagar.

At least 19 recordsLinked to original sources
PubMed2006

A randomized, parallel study of the safety and efficacy of 45 mg primaquine versus 75 mg bulaquine as gametocytocidal agents in adults with blood schizonticide-responsive uncomplicated falciparum malaria [ISCRTN50134587].

BACKGROUND: The WHO recommends that adults with uncomplicated P. falciparum successfully treated with a blood schizonticide receive a single dose of primaquine (PQ) 45 mg as a gametocytocidal agent. An earlier pilot study suggested that 75 mg of bulaquine (BQ), of which PQ is a major metabolite, may be a useful alternate to PQ. METHODS: In a randomized, partial blind study, 90 hospitalized adults with Plasmodium falciparum malaria that was blood schizonticide-responsive and a gametocytemia of > 55/microl within 3 days of diagnosis were randomized to receive single doses of either PQ 45 mg or BQ 75 mg on day 4. We assessed gametocytemia on days 8, 15, 22 and 29 and gametocyte viability as determined by exflagellation (2 degrees end point) on day 8. RESULTS: On day 8, 20/31 (65%) primaquine recipients versus 19/59 (32%) bulaquine recipients showed persistence of gametocytes (P = 0.002). At day 15 and beyond, all patients were gametocyte free. On day 8, 16/31 PQ and 7/59 BQ volunteers showed gametocyte viability (p = 0.000065). CONCLUSION: BQ is a safe, useful alternate to PQ as a Plasmodium falciparum gametocytocidal agent and may clear gametocytemia faster than PQ.

Adolescent↗
PubMed2005

Liposomal drug delivery system from laboratory to clinic.

The main objective of drug delivery systems is to deliver a drug effectively, specifically to the site of action and to achieve greater efficacy and minimise the toxic effects compared to conventional drugs. Amongst various carrier systems, liposomes have generated a great interest because of their versatility. Liposomes are vesicular concentric bilayered structures, which are biocompatible, biodegradable and nonimmumnogenic. They can control the delivery of drugs by targeting the drug to the site of action or by site avoidance drug delivery or by prolonged circulation of drugs. Amphotericin B (Amp B) remains the drug of choice in most systemic mycoses and also as a second line treatment for Kala azar. However, its toxic effects often limit its use. Although the liposome delivery system has been tried for several drugs, only a few have been used in patients due to the slow development of necessary large-scale pharmaceutical procedures. This paper reviews the development of the technique for liposomal Amphotericin B (L-Amp-LRC-1, Fungisome) drug delivery system in our laboratory in collaboration with the department of Biochemistry, Delhi University in India and proving the safety and efficacy of this preparation in clinical practice. It also attempts to compare the efficacy and benefits of our product for Indian patients with those of similar products and it includes facts from the publications that flowed from our work. As compared to conventional Amp B, Fungisome is infused over a much shorter period requiring a smaller volume and no premedication. It was found to be safe in patients who had developed serious unacceptable toxicity with conventional Amp B. In renal transplant patients, Fungisome did not produce any nephrotoxicity. Fungisome is effective in fungal infections resistant to fluconazole, conventional Amp B and in virgin and resistant cases of visceral leishmaniasis. The cost of any drug is of great significance, especially in India. We have therefore devoted a section of our review to the relative costs of our product and those of other commercially available products. This patient-worthy formulation is safe, efficacious and cheaper than the commercially available formulation of liposomal amphotericin B. The product has been patented and technology transferred to a pharmaceutical company for marketing. Results of postmarketing study also document safety and efficacy as observed in premarketing studies. A brief review of this work is provided here.

Amphotericin B↗
PubMed2005

Post-marketing study to assess the safety, tolerability and effectiveness of Fungisome: an Indian liposomal amphotericin B preparation.

BACKGROUND: In May 2003, an indigenously developed liposomal amphotericin B (Fungisome) was introduced in the Indian market for the treatment of systemic fungal infections and visceral leishmaniasis. The present post marketing study assessed the safety and effectiveness of Fungisome in actual clinical practice. SETTING AND DESIGN: Retrospective post marketing surveillance from four cities of India. METHODS: The present study was carried out for a period of 6 months (Jun-Nov 2004), a year after the introduction of the drug. A list of doctors who had prescribed and procured the drug was obtained from the distributor. Consent to participate and scrutinize the patients' source notes were obtained from the concerned doctors. All patients who had received Fungisome treatment were included. Data was collected from the patient's source notes on a predesigned proforma. They were then analyzed by descriptive statistics. Cost of Fungisome was calculated on the basis of dose used and number of days of treatment. RESULTS: Data were available for 109/144 patients from 35/40 physicians. Fungisome was administered at 1-3 mg/kg/day for 7-76 days. No serious adverse events related to the drug were observed in the study. Mild infusion-related adverse events were reported in 40 (36%), moderate in 11 (10%) of patients and severe in 2 (1.8%). None of the adverse events were certain to Fungisome exposure, 12 (11%) were probable, 28 (25 %) were possible, and 13 (11.9%) were unlikely. Of the 91 assessable patients (received at least eight doses of Fungisome) for efficacy complete response was observed in 67 (73.6%), 16 (17.5%) had partial responses, and 8 (8.7%) of patients had no response. The acquisition cost per day and per course treatment of different fungal infections ranged from (apprx) Rs 4500-8000 and 0.9-2.1 lakh respectively. CONCLUSION: This postmarketing study documents the safety, tolerability, effectiveness and cost advantage of indigenously developed liposomal amphotericin B in the treatment of systemic fungal infections and febrile neutropenia in actual clinical practice.

Adult↗
PubMed2004

Safety, tolerability, efficacy and plasma concentrations of diethylcarbamazine and albendazole co-administration in a field study in an area endemic for lymphatic filariasis in India.

Filariasis control programmes are moving towards a strategy of repeated single-dose mass treatment of endemic populations. Using a combination, such as albendazole (ALB) to diethylcarbamazine (DEC) gives both macrofilaricidal and anti-helmintic activity. However, the safety of the combination versus DEC alone should be established in field studies in large populations prior to incorporation into national programmes. The present study compared the safety, tolerability, and efficacy of single doses of DEC 6 mg/kg + ALB placebo with DEC 6 mg/kg + ALB 400 mg in populations living in two filariasis endemic villages in the district of Wardha in western India. The study was double blind, parallel group, and randomized. Safety and tolerability study were studied in males and females older than 5 years. Safety was assessed by monitoring if adverse events (AEs) over 5 days affected daily acivities. Subjects in the 2 treatment groups experienced insignificantly different effects on daily activities and the combination was shown to be safe. Efficacy was evaluated by microfilaraemia (Mf), immunochromatographic test (ICT) and ultrasonography (USG) at 0, 3, 6, and 12 months of follow up. The efficacy study enrolled 103 male patients (aged 18-50 years) in microfilariae positive, clinical disease and asymptomatic, amicrofilaremic groups. There was no significant difference in efficacy between groups at 12 months. Within the Mf positive group, significant differences were seen in microfilaraemia (P < 0.001) with both treatments, and in USG (P < 0.001 and P < 0.004 respectively), at 12 months. The present field study has shown the combination of DEC + ALB to be as safe as the single drug DEC and thus the combination can be put in use in the national filariasis control programmes. Both drugs were adequately absorbed. The study at present does not provide evidence for the greater efficacy of the combination at 12 months follow up. While the safety of the combination has been ascertained, the incorporation or otherwise of ALB into national programmes for greater efficacy must await results of studies with longer follow up.

Adolescent↗
PubMed2004

A prospective study evaluating the efficacy of a single, 45-mg dose of primaquine, as a gametocytocidal agent, in patients with Plasmodium falciparum malaria in Mumbai, India.

The efficacy of a single dose of 45 mg primaquine, as a gametocytocidal agent, was assessed in Mumbai, India, among adults with uncomplicated or severe Plasmodium falciparum malaria. All the patients investigated had been found gametocytaemic, with at least 56 gametocytes/microl blood, within the first 72 h of their illness. Those with uncomplicated malaria, like those with severe malaria, were randomized to receive or not receive primaquine. All the patients were followed up for 29 days post-admission, for gametocytaemia and gametocyte viability (as determined by exflagellation). Among those with uncomplicated malaria, six (27.3%) of the 22 who did not receive primaquine but only one (4.2%) of the 24 who did receive the drug, on day 4, remained gametocytaemic on day 29 (P < 0.05). Similarly, seven (31.8%) of the 22 severe cases who did not receive primaquine but only two (9.5%) of the 21 severe cases who received the drug, on day 8, were found gametocytaemic on day 15 (P < 0.05). While the single, 45-mg dose of primaquine recommended by the World Health Organization was effective in clearing gametocytes from the blood of > 90% of the present cases of malaria, > 4% of the patients with uncomplicated malaria and > 9% of those with the severe disease continued to harbour gametocytes in their peripheral blood 29 and 15 days after taking the primaquine, respectively.

Adolescent↗
PubMed2003

A randomized, crossover, assessor-blind study of the bioequivalence of a single oral dose of 200 mg of four formulations of phenytoin sodium in healthy, normal Indian volunteers.

The objective of the study was to compare the bioavailability of a single oral 200-mg dose of four brands of phenytoin sodium available in the Indian market. Dilantin, Epsolin, and M-toin were compared with Eptoin, which was taken as the reference standard. A randomized, assessor-blind, four-way crossover study was done in 12 healthy Indian volunteers. The study was conducted at a clinical pharmacology ward at King Edward VII Memorial Hospital, a tertiary referral center in Mumbai (Bombay). All 12 subjects received a single oral 200-mg dose of all the formulations with a 2-week washout period between the formulations. Blood samples for plasma phenytoin levels were collected at 0, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 48, and 72 hours. Safety was measured by pretreatment and posttreatment biochemical investigations, physical examination, and ECG. The pharmacokinetics of the four brands of phenytoin were calculated by maximum plasma concentration (C(max)), time to reach C(max) (t(max)), area under the concentration versus time curve for time 0 to 72 hours (AUC(0-72)), and from time 0 to infinity (AUC(0- infinity)). For all brands, 90% CI of all untransformed and log transformed pharmacokinetic parameters failed to remain within prescribed limits of 80% to 120% for untransformed data and 80% to 125% for log transformed data. Since phenytoin obeys Micheles Mentens kinetics, the AUC methodology used for comparison would give only an approximate indication of relative bioavailability. M-toin was shown to be bioinequivalent to Eptoin. The other comparisons indicate but do not prove bioinequivalence of the other brands. The results of the study show that in India switching phenytoin brands could have significant implications and is not advisable once a patient is carefully titrated on one formulation.

Adult↗
PubMed2003

Treatment of neonatal candidiasis with liposomal amphotericin B(L-AMP-LRC-1): phase II study.

A liposomal amphotericin B preparation (L-AMP-LRC-1) has been developed and tested successfully in adults by us. This preparation was administered to 23 neonates with candidiasis in an open phase II study. All the 14 assessable patients responded completely to the L-AMP-LRC-1 therapy given at 1 mg/kg for 28 days. Compared to AmBisome, another liposomal formulation of amphotericin B, L-AMP-LRC-1 was effective at lower dose in neonatal candidiasis. Thus L-AMP-LRC-1 appears to be an effective and low cost drug for the treatment of candidiasis.

Amphotericin B↗
PubMed2003

Diagnostic and prognostic utility of rapid strip (OptiMal and Paracheck) versus conventional smear microscopy in adult patients of acute, uncomplicated P. falciparum malaria in Mumbai, India.

OBJECTIVES: The present study compared the diagnostic and prognostic utility of two rapid tests the (Paracheck and OptiMal) versus conventional smear microscopy. METHODS: Using two independent microscopists we carried out the three tests in 31 adult cases of smear positive, acute, uncomplicated Plasmodium falciparum malaria. All three tests were done pretreatment, and on Days 8, 15 and 29. RESULTS: Compared to microscopy, the Paracheck had a sensitivity of 100%, while the OptiMal had a sensitivity of 83.7%. The lower sensitivity of OptiMal resulted from misidentification by both microscopists of 6/31 cases as Plasmodium vivax. As a follow up tool, the OptiMal was better than Paracheck, due to the earlier disappearance of the parasite LDH. Also in the Paracheck, between microscopists, there was a significant difference in reading the tests, on Days 8 and 15. CONCLUSION: Our study reiterates, the continued utility of conventional smear microscopy.

Adolescent↗
PubMed2003

A cost-effectiveness analysis of three antimalarial treatments for acute, uncomplicated Plasmodium falciparum malaria in Mumbai, India.

BACKGROUND: Malaria is a major public health problem representing 2.3% of the overall global disease burden. The cost of treatment of malaria continues to rise as older drugs and insecticides become less effective and are replaced by more effective, but also more expensive products. METHODS: A post-hoc pharmacoeconomic analysis (direct and indirect costs only) of three antimalarials, chloroquine, mefloquine and co-artemether, was carried out to address the problem of switch to a more expensive first-line antimalarial in the face of growing chloroquine resistance. RESULTS: From the perspective of a large public hospital, it was seen that in an area of high grade chloroquine resistance, the total expenditure on patients who fail chloroquine would exceed the excess expenditure on mefloquine when the RII + RIII resistance exceeded 9%. CONCLUSIONS: Switch to a more expensive drug like mefloquine as a first-line option would be cost-effective when the moderate-severe chloroquine resistance exceeded 9%.

Antimalarials↗
PubMed2002

The use and safety of non-allopathic Indian medicines.

Non-allopathic Indian medicines, referred to elsewhere in the world as complementary and alternative medicine have gathered increasing recognition in recent years with regard to both treatment options and health hazards. Ayurveda, Siddha, Unani and homeopathy are practiced in India as non-allopathic systems. These systems comprise a wide range of therapeutic approaches that include diet, herbs, metals, minerals, precious stones and their combinations as well as non-drug therapies. Ayurveda is the oldest system of medicine in the world and by far the most commonly practiced form of non-allopathic medicine in India, particularly in rural India, where 70% of the population lives. The difference between modern medicine and these systems stems from the fact that the knowledge base of many of the above systems, unlike Western medicine, is based on years of experience, observations, empiricism and intuition and has been handed down generations both through word of mouth and treatises. The focus on non-allopathic systems of medicine in India can be attributed to various causes including a need to revive a rich tradition, the dependency of 80% of the country's population on these drugs, their easy availability, increasing worldwide use of these medicines, the lack of focused concerted scientific research and the abuse of these systems by quacks. Elsewhere, the increasing use of herbal products worldwide and the growth of the herbal product industry has led to increasing concern regarding their safety. The challenges in these non-allopathic systems relate to the patient, physician, regulatory authorities, the abuse/misuse of these medicines, quality and purity issues. Safety monitoring is mandated by a changing ecological environment, the use of insecticides, new manufacturing techniques, an as yet unregulated pharmaceutical industry, the availability of combinations of herbs over the counter and not mentioned in ancient Ayurvedic texts, and the need to look at the active principles of these medicines as potential chemotherapeutic agents. The Indian traditional medicine industry has come a long way from the times when it was considered unnecessary to test these formulations prior to use, to the introduction of Good Manufacturing Practice guidelines for the industry. However, we still have a long way to go. The conflict between the traditional practitioners and the purists demanding evidence of safety and efficacy needs to be addressed. There is an urgent need for the practitioners of the allopathic and non-allopathic systems to work together to optimise the risk-benefit profile of these medicines.

Clinical Trials as Topic↗
PubMed2002

Open label, randomised, comparative phase III safety and efficacy study with conventional amphotericin B and liposomal amphotericin B in patients with systemic fungal infection.

OBJECTIVE: To compare conventional amphotericin B (c-amp B) and liposomal amphotericin B (L-AMP-LRC-1-India) in patients with systemic fungal infection in open, randomized, comparative, laboratory blind, phase III safety and efficacy study. MATERIAL AND METHODS: Formulation of liposomal amphotericin B - L-AMP-LRC-1, containing natural phospholipids, was prepared and tested at the Department of Clinical Pharmacology, Seth GS Medical College and KEM Hospital, Mumbai, India. Patients suffering from proven systemic fungal infection, were treated with c-amp B or L-AMP-LRC-1 with 17 patients in each group. Data was compared for the safety and efficacy. RESULTS SAFETY: L-AMP-LRC-1 was better tolerated than c-amp B. Out of the 695 infusions of c-amp B fever occurred on 25.04% occasions in 68.42% patients, while it occurred on 2.09% occasions out of 767 infusions (in 30.43% patients of L-AMP-LRC-1. Chills occurred on 16.83% and 1.17% occasions after c-amp B and liposomal amphotericin B respectively. Other adverse effects observed on 0.2-5% of occasions were: headache, nausea, vomiting, palpitation and dizziness occurring more frequently in c-amp B group. The L-AMP-LRC-1 did not cause bronchospasm at 1 mg/kg dose in a patient who developed bronchospasm to 0.1 mg/kg dose of c-amp B. The L-AMP-LRC-1 was found to be less nephrotoxic than c-amp B and could be administered to patients who had renal problems or had undergone renal transplant. L-AMP-LRC-1 caused less hypokalemia than c-amp B. Effficacy: 17/17 patients in L-AMP-LRC-1 group and 14/17 in c-amp B group had complete response (100% and 82.35% response rate). The number of infusions and dose of amphotericin B and L-AMP-LRC-1 used were similar and required individualization of duration of treatment (in cases where response to fixed duration was not observed). All the patients were treated with 0.5 to 1.0 mg/kg/day dose of L-AMP-LRC-1 (except one patient required 2 mg/kg dose). This is markedly different from other marketed liposome and lipid formulations, which are recommended at higher (3-5 mg/kg) doses every day. At the same time L-AMP-LRC-1 being prepared from naturally occurring lipids is expected to cost at least one-third of the marketed formulation. Thus cost of every day treatment would be very much less compared to other delivery systems. Thus L-AMP-LRC-1 will be an economical and safe treatment option available to the physicians for the treatment of systemic fungal infection.

Adolescent↗