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.

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.

Double blind, placebo controlled trial on the cytoprotective effect of misoprostol in subjects with rheumatoid arthritis, osteoarthritis and seronegative spondarthropathy on NSAIDs.

Ninety arthritic patients were randomly allotted to receive misoprostol 200 micrograms thrice daily or placebo, for 4 weeks, while they were started on various NSAIDs. While upper gastrointestinal symptoms occurred equally in both groups, patients on placebo had significantly more post-therapy abnormal endoscopy findings. Misoprostol was well tolerated without any adverse side effects; it did not interfere with the therapeutic efficacy of the NSAIDs. Arthritic patients requiring long term NSAID therapy appear to benefit from misoprostol because of its cytoprotective effect on the gastrointestinal mucosa.

Evaluation of the efficacy and safety of azathioprine (Azoran), in fresh cases of renal homotransplantation.

In a randomised, controlled study, the efficacy and safety of an indigenously developed azathioprine formulation, Azoran/1000 (Searle), was compared with an imported formulation Imuran, as an immunosuppressive agent in fresh cases of renal transplantation. All 14 patients enrolled into the trial completed the study period were analysed. There were 8 episodes of rejection, 4 in each group. All these cases responded to pulse steroids. There was no instance of severe bone marrow suppression or hepatitis in either group and none of the patients had any drug related adverse effects. The results of this study show that Azoran is equiefficacious and safe as an immunosuppressive drug in renal transplants and compares satisfactorily in all respects with the imported formulation Imuran and has the added advantage of being easily available and less costly.

Susceptibility pattern of bacterial isolates to lomefloxacin.

The in vitro susceptibility pattern with respect to lomefloxacin was determined in case of 1009 bacterial isolates from clinical specimens with varying susceptibility to commonly used antimicrobial agents. The MIC50 and MIC90 values of lomefloxacin for the Gram negative bacilli showed susceptibility value ranging between 0.12 to 4.0 micrograms/ml, while 90 per cent of the streptococci tested were inhibited only at 16 micrograms/ml. Lomefloxacin was comparable in activity to enoxacin and ciprofloxacin but it was more active than norfloxacin and nalidixic acid.