Steady state pharmacokinetic profile of indomethacin in elderly patients and young volunteers

The steady-state pharmacokinetic profile of indomethacin was examined in twelve healthy volunteers (4 m, 8 f; 20-34 y) and in 12 elderly subjects (7 m, 5 f; 70-88 y). Two formulations of indomethacin were examined, providing duplicate data for each subject group. The subjects received each formulation of indomethacin (25 mg tid) for 6 days in a single blind crossover fashion. On day 7, after an overnight fast, a final 25 mg dose of indomethacin was given and plasma concentrations measured over the following 12 h. Kinetic parameters Cpmin, Tmax and AUC (0-12 h) were determined. There were no differences in the pharmacokinetic parameters between young and elderly subjects or between data for the two formulations of indomethacin. AUC values (micrograms.ml-1.h), for example, for the two formulations in the young subjects were 5.85 and 6.85 while the values for the elderly subjects were 6.55 and 6.50 respectively. When each treatment period was considered independently there was a significant difference between young and elderly subjects with regard to compliance. The rates of non compliance (over and under compliance) using a capsule count technique were, however, low with a mean maximum value of 5.8% being recorded for the elderly subjects.

Randomised controlled trial of ranitidine versus omeprazole in combination with antibiotics for eradication of Helicobacter pylori

This study compared high dose ranitidine versus low dose omeprazole with antibiotics for the eradication of H pylori. 80 patients (mean age 48 years, range 18-75) who had H pylori infection were randomised in an investigator-blind manner to either a two-week regime of omeprazole 20 mg daily, amoxycillin 500 mg tid and metronidazole 400 mg tid (OAM), or ranitidine 600 mg bd, amoxycillin 500 mg tid and metronidazole 400 mg tid (RAM), or omeprazole 20 mg daily and clarithromycin 500 mg tid (OC), or omeprazole 20 mg daily and placebo (OP). H pylori was eradicated in 6 of 19 patients in the OAM group (32%); 8 of 18 in the RAM group (44%), 4 of 15 in the OC group (27%); none of 18 in the OP group (0%). [<P0.005 for OAM, RAM, OC vs OP; P = N.S. between OAM, RAM, OC]. Overall metronidazole resistance was unexpectedly high at 58%. Eradication rates in metronidazole sensitive patients were 71% (5/7) and 100% (3/3) for OAM and RAM respectively. In conclusion, H pylori eradication rates using high dose ranitidine plus amoxycillin and metronidazole may be similar to that of low dose omeprazole in combination with the same antibiotics for omeprazole with clarithromycin. Overall eradication rates were low due to a high incidence of metronidazole resistance but were higher in metronidazole-sensitive patients. Even high dose ranitidine with two antibiotics achieves a relatively low eradication rate. These metronidazole-based regimens cannot be recommended in areas with a high incidence of metronidazole resistance.