Steady-state pharmacokinetics of metronidazole in Crohn's disease
โ Scribed by Okponanabofa Eradiri; Fakhreddin Jamali; Alan B. R. Thomson
- Publisher
- John Wiley and Sons
- Year
- 1987
- Tongue
- English
- Weight
- 505 KB
- Volume
- 8
- Category
- Article
- ISSN
- 0142-2782
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โฆ Synopsis
The pharmacokinetics of metronidazole (MTZ) were studied in six Crohn's disease patients after multiple oral daily doses of 250, 500, 750, and 1OOOmg day-'. Pharmacokinetic indices were found to be independent of the dose administered. The half-life, volume of distribution and oral clearance of metronidazole were 9-5 * 2-1 h, 0.732 k 0.094 1 kg-' and 0.921 ? 0.175 (ml min-') kg-' (mean ? SD), respectively. A strong linear correlation ( r = 0.95) was found between the volume of distribution of MTZ and the patients' total body weight. The percentage of dose of metronidazole excreted in urine as the intact drug and metabolites as well as glucuronic acid conjugates ranged from 34.7 k 7.4 to 58.9 k 5.2. Both plasma and urine data exhibited very large inter-patient variations. However, intra-patient variations were negligible. Strong positive linear correlations were observed between the dose and the areas under the plasma concentration versus time curves, peak plasma concentrations as well as cumulative urinary excretion of the drug and its metabolites. It is concluded that in Crohn's disease, the pharmacokinetics of MTZ and its metabolites are linear and that the drug concentrations are dependent on the total body weight.
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Ten children with rheumatoid arthritis, aged 7-16 y and weighing 20-63 kg, were treated with piroxicam mean dose 0.4 mg.kg-1 once daily for 2 weeks. On Day 15, blood was sampled from 2-120 h after the last dose. The Cmax for piroxicam ranged from 3.6 to 9.8 (mean 6.6) mg.l-1 and its half-life by log