Post-marketing surveillance of arteether in malaria.

OBJECTIVE: To undertake post-marketing surveillance (PMS) of arteether (E-Mal) with the aim of obtaining feedback from clinicians regarding its safety, tolerability, efficacy and adverse event profile in patients of P. falciparum malaria. METHOD: Post-marketing surveillance proforma to collect data from clinicians using arteether (E-Mal) was provided to institutions/nursing homes and hospitals where Arteether (E-Mal) was available for use in treatment of P. falciparum malaria. These clinicians were informed about the need and relevance of providing this feedback regarding their reexperience on E-Mal therapy on predesigned proforma. Duly filled proformas were received by Central Drug Research Institute, Lucknow for data analysis, documentation and conclusions regarding E-Mal therapy. RESULT: A total of 300 reports were received for analysis from states of Bihar, Gujarat, Madhya Pradesh, Maharashtra, Rajasthan and Uttar Pradesh. The results show that 294 cases (98%) were cured, five cases improved and one patient did not show any change in the clinical status. The side effects (headache, nausea, vomiting and giddiness) reported in the proforma of 14 cases were mild in nature and no causal relationship with arteether could be ascertained. CONCLUSION: An indepth analysis of these 300 reports confirmed the safety, highlighted excellent tolerability and further proved the efficacy of three-day schedule of arteether (IMI) for treatment of malaria. Arteether should not be used in P. Vivax malaria (E-Mal) except when smear is positive for both (P. falciparum and P. vivax). In such a situation risk-benefit should be carefully evaluated before advocating the use of E-Mal therapy. The post-marketing surveillance is continuing and it is hoped that with more feedback from the clinicians from various parts of the country PMS data on this novel antimalarial drug (E-Mal) would further be documented.

Multicentric clinical trials for safety and efficacy evaluation of alpha;beta arteether in complicated P. falciparum malaria.

OBJECTIVE: To evaluate efficacy of alpha;beta arteether in patients of P. falciparum malaria presenting with complications was undertaken in a multicentric clinical trial. METHOD: Each patient who consented to undergo clinical trial with parenteral Arteether was treated with a fixed dose schedule of Arteether given intramuscularly in a dose of 150 mg once a day on three consecutive days. Every patient was followed upto 28 days with clinical, haematological and parasitological monitoring every day upto one week and thereafter at 14, 21 and 28 days. The response was assessed in terms of fever clearance time, parasite clearance time, cure rate and parasite reappearance rate. RESULTS: A total of 211 patients of P. falciparum malaria were included in the study from four centres (Bhilai, Guwahati, Jamshedpur and Rourkela). Results of this study showed that fever clearance time ranged between 24-168 hours, parasite clearance time ranged between 24-120 hours and overall mortality ranged between 4-8.5%. Out of 211, only 14 patients expired during the study, of these, 10 patients expired within first two days i.e. before completing the three day schedule of arteether therapy. Tolerability to arteether injection was good in all these patients and no untoward effects were experienced or reported during the study. Overall cure rate observed in these studies was 93%. CONCLUSION: This study shows a rapid parasite and fever clearance in patients of complicated P. falciparum malaria.

A multicentric study with arteether in patients of uncomplicated falciparum malaria.

Two hundred and sixty seven patients of uncomplicated P. falciparum malaria completed study in a multicentric phase III clinical trial of Arteether. Arteether was given intramuscularly in a dose of 150 mg daily for three consecutive days. Each patient was followed upto 28 days of alpha, beta arteether therapy. The cure rate was 97% with fever clearance time between 1-7 days (24-168 hours) and parasite clearance time between 1-3 days (24-72 hours). Parasite reappearance rate was found to be 3% and reported at only three of the centres. Following the treatment no adverse effect was observed on haematological, biochemical and vital clinical parameters.

Effectiveness of alpha-beta arteether in clearing Plasmodium falciparum parasitemia in central India (Madhya Pradesh).

Forty-six patients (25 Females + 21 Males) of uncomplicated Plasmodium falciparum in districts Jabalpur and Mandla of central India (Madhya Pradesh) were administered alpha-beta arteether (an ethyl derivative of qinghaosu), intramuscularly for 3 consecutive days (150 mg once a day). The results revealed that there was rapid control of fever in all the patients without administration of any antipyretic drug. The mean parasite clearance time was 30.78 +/- 10.92 hours and recrudescence/reinfection rate was 6.7% within 28 days. Study indicates that arteether, besides being a potent and fast acting schizontocidal drug, also exhibited gametocytocidal action on P. falciparum.

Detection of anti-PPD IgG antibody and PPD-induced delayed type hypersensitivity in anterior uveitis patients.

Present study relates to the results of anti-PPD IgG, anti-A60 and antinuclear antibodies and PPD-induced delayed type hypersensitivity (DTH) in 17 anterior uveitis, (AU) patients. Results of anti-PPD IgG assay revealed detection of higher mean antibody level (O.D. 0.11 +/- 0.06) compared to healthy controls (O.D. 0.04 +/- 0.03), other eye disease controls (O.D. 0.05 +/- 0.003) and leprosy controls (O.D. 0.03 +/- 0.03). Anti-A60 IgM antibody assay revealed insignificant differences in mean antibody levels between various groups. Four of 17(23.5%) AU patients and 1(5.8%) subject each, belonging to other eye disease and healthy control groups had raised anti-nuclear antibody index. Findings of PPD skin test revealed detection of moderate to strong (2 to 4+) reactivity in 14 (82%). AU patients. Conversely, 13(76%) healthy controls and 8(47%) other eye disease controls gave mild (1+) reactivity. Results of this study suggested possible role of hypersensitivity to mycobacterial antigens in pathogenesis of anterior uveitis.

Clinical pharmacological studies on centpropazine--a new antidepressant compound.

Single oral doses of 10 to 160 mg centpropazine, a new antidepressant (synthesized by CDRI, Lucknow, India) were administered to groups of 4-5 male volunteers, each dose being interspersed with placebo in a double blind, non-crossover study by random distribution. The drug was well tolerated. Drowsiness, heaviness, weakness and/or headache were reported only at doses of 120 mg and above. No adverse effect was noted in various laboratory tests, ECG or vital parameters. In a multiple dose study, volunteers received 40 or 80 mg centpropazine daily for 4 wk. Mild restlessness and insomnia were observed in some subjects receiving 80 mg dose. In this study also no effect was observed in various laboratory tests, ECG or vital parameters.

Clinical trials with gugulipid. A new hypolipidaemic agent.

Multicentric clinical trials of the efficacy of gugulipid conducted at Bombay, Bangalore, Delhi, Jaipur, Lucknow, Nagpur and Varanasi have been reported. Two hundred and five patients completed 12 week open trial with gugulipid in a dose of 500 mg tds after 8 week diet and placebo therapy. One patient showed gastrointestinal symptoms which did not necessitate withdrawal of the drug. A significant lowering of serum cholesterol (av. 23.6%) and serum triglycerides (av. 22.6%) was observed in 70-80% patients Double-blind, crossover study was completed in 125 patients with gugulipid therapy and in 108 patients with clofibrate therapy. Two patients had flu-like syndrome with clofibrate and opted out from the study. With gugulipid the average fall in serum cholesterol and triglycerides was 11 and 16.8% respectively and with clofibrate 10 and 21.6% respectively. The lipid lowering effect of both drugs became evident 3-4 week after starting the drug and had no relationship with age, sex, and concomitant drug intake. Hypercholesterolaemic patients responded better to gugulipid therapy than hypertriglyceridaemic patients who responded better to clofibrate therapy. In mixed hyperlipidaemic patients response to both drugs was comparable. HDL-cholesterol was increased in 60% cases who responded to gugulipid therapy. Clofibrate had no effect on HDL-cholesterol. A significant decrease in LDL-cholesterol was observed in the responder group to both drugs.