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Metronidazole kinetics in patients with acute renal failure on dialysis: a cumulative study
Abstract:
Nine patients with acute renal failure who were undergoing dialysis at intervals depending on clinical state were injected with metronidazole, 7.5 mg . kg-1 iv every 8 hr. Plasma samples were drawn during the 8 hr after the first infusion, during the first dialysis session, and during the course of the fourth infusion after the first three dialysis sessions. Metronidazole and its two main metabolites (alcohol [M1] and acid [M2]) were assayed by HPLC. The plasma t 1/2 of metronidazole (6.8 hr) is of the same order as that in healthy subjects. M1 and M2 plasma levels increased continuously until the next infusion. Dialysis clearances of metronidazole and its metabolites were about 60 ml . min-1; 25% of metronidazole in the body at the beginning of hemodialysis was eliminated. The corresponding apparent t 1/2 s are 3.3 hr (metronidazole), 8.0 hr (M1), and 7.9 hr (M2). In patients with acute renal disease under hemodialysis, there was no cumulation of metronidazole and its metabolites; hence there is no need for change in dosage regimen.
Insights
Metronidazole dosing in acute renal failure patients undergoing hemodialysis does not require adjustment. Studies show no accumulation of metronidazole or its metabolites during dialysis, supporting the standard regimen.
Area of Science:
- Pharmacokinetics
- Nephrology
- Infectious Diseases
Background:
- Metronidazole is commonly prescribed for anaerobic infections.
- Acute renal failure (ARF) and its treatment with hemodialysis can alter drug pharmacokinetics.
- The impact of hemodialysis on metronidazole and its metabolite clearance in ARF patients is not well-established.
Purpose of the Study:
- To investigate the pharmacokinetics of metronidazole and its metabolites in patients with acute renal failure undergoing hemodialysis.
- To determine if metronidazole or its metabolites accumulate during standard hemodialysis regimens.
- To assess the need for dosage adjustments in this patient population.
Main Methods:
- Nine patients with ARF undergoing intermittent hemodialysis received intravenous metronidazole (7.5 mg/kg) every 8 hours.
- Plasma samples were collected at various time points, including pre- and post-dialysis.
- Metronidazole and its primary metabolites (M1 and M2) were quantified using High-Performance Liquid Chromatography (HPLC).
Main Results:
- The plasma half-life (t 1/2) of metronidazole in ARF patients was comparable to healthy individuals (6.8 hours).
- Metabolite levels (M1 and M2) increased between doses but did not accumulate significantly.
- Hemodialysis effectively cleared metronidazole and its metabolites, with an estimated clearance of 60 ml/min, reducing the body burden by 25%.
Conclusions:
- Metronidazole and its metabolites do not accumulate in patients with acute renal failure undergoing hemodialysis.
- The standard metronidazole dosage regimen can be safely used in ARF patients on hemodialysis.
- No modification of the metronidazole dosing schedule is necessary for this patient group.