Evaluation of clinical efficacy and safety of once daily topical administration of 1% oxiconazole cream and lotion in dermatophytosis : an open label, non comparative multicentre study.

The clinical efficacy and safety of once daily topical administration of 1% oxiconazole cream and lotion was assessed in an open label, non comparative trial in tinea cruris, tinea corporis and tinea pedis patients. In treated patients, severity scores of erythema, pruritus, scaling, vesicles, papules and burning showed a progressive fall over a period of 4 weeks at all the study centres. With lotion, mean percentage improvement of symptoms varied from 35% (week 1) to 87.6 - 98.7% (week 4). With cream, it varied from 35% (week 1) to 82.5 - 99.5% (week 4). Overall global evaluation response showed clear, excellent and good response in 60%, 21% and 17% of the patients treated with lotion respectively. With cream, excellent and good response was observed in 71%, 10% and 16% of the patients respectively. In T. pedis patients, clear, excellent and good response was observed in 4/8, 2/8 and 1/8 patients respectively with lotion. Cream showed clear (8/15), excellent (4/15) and good (1/15) in these patients. None of the patients out of 178 enrolled, reported any side effect during the trial.

Phase I pharmacokinetic study of a new 3-azinomethyl-rifamycin (rifametane) as compared to rifampicin.

An open randomized cross-over study was conducted in 8 healthy male volunteers to study the pharmacokinetic pattern and the safety of a 300-mg single oral dose of a new 3-azinomethyl-rifamycin (USAN rifametane, SPA-S-565) compared with 300 mg of conventional rifampicin. The pharmacokinetic profiles of rifametane were significantly more favorable than those of rifampicin. The serum peak value was 7.82 microg/ml for rifametane and 4.04 microg/ml for rifampicin (p < 0.001); the elimination half-life was 10.58 h for rifametane and 1.89 h for rifampicin (p < 0.001); area under the serum concentration curve from 0 to infinity was 142.3 microg.h/ml for rifametane and 19.9 microg.h/ml for rifampicin (p < 0.001); the mean residence time was 18.05 h for rifametane and 3.93 h for rifampicin (p < 0.001). Rifametane showed a good safety profile after the 300-mg single oral dose. Three volunteers developed a mild headache, metallic taste and slightly elevated temperature for 3-4 h, which subsided without medication. Clinically or statistically significant changes in laboratory parameters were not found between baseline and posttreatment values.

Pharmacokinetic profile of a new 3-azinomethyl rifamycin (SPA-S-565) in volunteers as compared with conventional rifampicin.

The pharmacokinetics and tolerance of a single oral dose (150 mg) of a new 3-azinomethyl rifamycin (SPA-S-565, USAN rifametane) was compared with 150 mg of conventional rifampicin in six healthy volunteers. The mean maximum concentration (Cmax) of SPA-S-565 was 3.94 +/- 0.26 micrograms/ml, and resulted significantly higher as compared with the Cmax after rifampicin, which was 2.89 +/- 0.20 micrograms/ml. The mean maximum time (tmax) for SPA-S-565 was 2.1 +/- 0.3 h as compared with that of rifampicin, which was 1.6 +/- 0.3 h, the difference between these values not being statistically significant. The elimination half-life (t1/2) of SPA-S-565 was 17.5 +/- 2.6 h in contrast to the half-life of 2.8 +/- 0.26 h seen with rifampicin; the difference was found to be highly significant. The mean area under the serum concentration curve from 0 to the last detectable concentration (AUC0-t) and the mean area under the serum concentration-versus-time curve from 0 to infinity (AUC0-infinity) of SPA-S-565 were almost six times than those obtained with conventional rifampicin. The differences between the two compounds were highly significant. In all cases except one volunteer all the biochemical parameters remained within normal range following single oral dose administration of SPA-S-565. In one volunteer, although there was a slight rise in serum alkaline phosphatase above the normal range, the original value itself was at the very upper limit of the normal range (i.e., 80 IU/L). Although there was a significant increase in the levels of serum alkaline phosphatase, serum gamma-glutamyl transpeptidase (GGTP) and serum amylase levels, 24 h following the administration of SPA-S-565 these levels remained within the normal range.

Comparative biorelease study of fluticasone in combination with antibacterial (Neomycin) and or antifungal (coltrimazol, miconazole) agents by histamine percutaneous reaction method in healthy volunteers.

Fluticasone propionate is a novel, potent and topically active synthetic corticosteroid preparation with a much reduced potential, in relation to its anti-inflammatory potency, for unwanted systemic side effects. It is indicated for the treatment of eczema, dermatitis etc. The objective of the present study was to evaluate and compare the biorelease of fluticassone with placebo (base formulation); its combination with antifungal (miconazole, clotrimazole) and / or antibacterial agents based on the attenuation of histamine induced wheal and flare reaction and flare intensity (on visual analouge scale) by McNemar test. In the present study, fluticasone alone and in combination with clotrimazole, miconazole and neomycin significantly reduced the wheal and flare response of histamine prick test. The flare intensity response was also significantly inhibited by these treatments. Furthermore, there was no difference in the anti-inflammatory activity of various treatment groups. It may, therefore, be concluded that antibacterial (neomycin) and / or antifungal (miconazole, clotrimazole) agents in combination with steroid (fluticasone) do not alter the pharmacodynamic response of the latter.

Cefuroxime axetil in the treatment of Salmonella typhi infection (enteric fever) in adults.

A study to evaluate the efficacy and safety of Cefuroxime Axetil in enteric fever was carried out in 30 adult hospitalised patients of either sex. A positive blood culture for S. typhi and sensitivity to cefuroxime axetil were confirmed prior to treatment. On admission, the baseline signs and symptoms were recorded and treatment initiated with cefuroxime axetil in a dose of 500 mg bd; which was continued for 7 days after normalization of temperature. The various clinical parameters were followed up daily during the treatment period and discharge permitted on normalization of temperature. Blood culture for S. typhi was repeated 3 days after stopping treatment. Follow-up Widal, stool and urine cultures were done wherever possible to check for relapse or carrier state. All the patients responded clinically to treatment and had bacteriologically negative blood cultures by the end of 14 days treatment. 87% of the patients responded within 7 days of treatment of which 60% were graded as Excellent responders as they responded within 4 days itself; while 13% took a longer time to respond. There were no relapses or carrier state as indicated by negative follow-up stool cultures. Only one patient reported a side-effect of mild headache confirming the safety of the drug. We conclude that Cefuroxime axetil in a dose of 500 mg bd is an effective and safe drug in the treatment of multi drug resistant enteric fever.

Comparative evaluation of the clinical efficacy and safety of ondansetron and metoclopramide in the prophylaxis of emesis induced by cancer chemotherapy regimens including cisplatin.

The efficacy and safety of ondansetron was evaluated and compared with metoclopramide in 93 patients receiving cisplatin containing cancer chemotherapy in a randomized, parallel group study. 8 mg Ondansetron i.v. was administered prior to chemotherapy followed by two further doses of 8 mg i.v. over the first 24 hours. Ondansetron 8 mg b.d. was then administered orally for the next 5 days. The metoclopramide dosage was 20 mg i.v. prior to chemotherapy followed by 2 i.v. doses of 10 mg each, 4 hours apart. For the next 5 days, an oral dose of 20 mg metoclopramide was administered. The anti-emetic efficacy of ondansetron as a prophylactic treatment was found to be significantly more effective than metoclopramide both during the acute and delayed phase of nausea and vomiting. Both treatments were well tolerated with no reported side-effects.

Response to single dose of tetanus vaccine in subjects with naturally acquired tetanus antitoxin.

Tests among 410 Indians not artificially immunised against tetanus showed that 80% had measurable antitoxin. Single doses (100 Lf or 250 Lf) of a potent tetanus toxoid were given to such individuals with naturally acquired antitoxin. The 100 Lf dose produced on average a ten-fold rise in antibody level, and the 250 Lf dose a twenty-fold rise. In adults who had been artificially immunised, a 5 Lf dose produced a four-fold to ten-fold rise in antibody level. In infants three doses of triple vaccine produced satisfactory antitoxin concentrations. The levels of antibody achieved after a single 250 Lf dose should protect for 5 years. Single-dose vaccination may be better than the conventional three-dose scheme for a population that is unlikely to comply with a three-dose regimen and in whom naturally acquired antitoxin is associated with partial tolerance to tetanus toxoid. Naturally acquired antitoxin in Indians is probably the result of chronic clostridial contamination of the small bowel. This contamination can induce immune tolerance in the gut and systemically and may be the reason for the poor responses to vaccination in all except infants.