The pharmacokinetics of oral and intravenous metronidazole in man

The pharmacokinetics of metronidazole were studied after oral and intravenous administration to seven patients with Crohn's disease and five patients with ulcerative colitis. The oral/intravenous availability ratio was 0.97 +/‐ 0.2 in the Crohn's patients and 0.90 +/‐ 0.1 in the colitics (mean +/‐ s.e. mean). Plasma clearance was 3.24 +/‐ 0.2 l h‐1 and 4.1 +/‐ 0.5 l h‐1, respectively. These differences were not statistically significant. Ten of the patients on long term sulphasalazine were studied to observe the effect of 2 weeks metronidazole therapy on plasma sulphapyridine concentration. The sulphapyridine concentration changed from 22.1 +/‐ 2.0 micrograms ml‐1 to 15.95 +/‐ 4.5 micrograms ml‐1 in the Crohn's patients and 26.0 +/‐ 6.0 micrograms ml‐1 to 36.4 +/‐ 8.5 micrograms ml‐1 in the colitis group, pre‐ and post‐metronidazole. These differences were not statistically significant. These results suggest that metronidazole does not interfere with diazo‐link splitting of sulphasalazine and that patients with Crohn's disease handle metronidazole in a similar manner to patients with colitis.

Section: Sulphapyridinesupporting

confidence: 91%

Disposition of metronidazole and its effects on sulphasalazine metabolism in patients with inflammatory bowel disease.

Shaffer¹,

Kershaw²,

Houston³

1986

“…W. During repeated dosing of healthy subjects accumulation of metronidazole occurs and steady-state plasma metronidazole concentrations rise to about twice the concentrations observed after a single dose (Houghton et al, 1979b). The results of this study suggest that in patients with renal insufficiency, no further accumulation of metronidazole will occur.…”

Section: Discussionmentioning

confidence: 57%

“…The sex or age of subjects has been shown not to markedly alter the pharmacokinetics of intravenous metronidazole (Houghton et al, 1979b). Weight differences may be expected to proportionately alter AUC and volume of distribution parameters in Table 1 (Gulaid et al, 1978).…”

Section: Introduction Proceduresmentioning

confidence: 98%

“…Urinary excretion of metabolite I was similar in healthy volunteers to that in patients with moderate renal insufficiency, but was reduced in patients with severe renal insufficiency to only 25% of that observed in healthy volunteers (Table 2). This hydroxy metabolite is eliminated by both renal and hepatic routes (Houghton et al, 1979b), so that any decrease in the urinary excretion which is not compensated by an increase in hepatic elimination will extend the half-life of metabolite I.…”

Section: Introduction Proceduresmentioning

confidence: 99%

See 1 more Smart Citation

Pharmacokinetics of metronidazole in patients with varying degrees of renal failure.

Houghton¹,

Dennis²,

Gabriel³

1985

1 Twenty-nine patients with varying degrees of renal insufficiency were given a single intravenous dose of metronidazole (500 mg). Plasma and urinary concentrations of metronidazole and two major metabolites were determined using a specific high performance liquid chromatographic assay. 2 The pharmacokinetic parameters of metronidazole elimination half-life, area under the metronidazole concentration against time curve, apparent volume of distribution, metronidazole clearance and predicted degree of accumulation of metronidazole on repeated dosing were not statistically significantly affected by renal inadequacy of any degree. 3 The urinary excretion of metronidazole in patients with moderate or severe renal insufficiency was approximately half the value in healthy volunteers. The renal clearance of metronidazole was significantly greater in healthy volunteers compared to renally insufficient patients, but accounted for less than 10% of the total metronidazole clearance in all groups. 4 The elimination half-life and predicted accumulation (on three times daily dosing) of metabolite I [1-(2-hydroxyethyl)-2-hydroxymethyl-5-nitroimidazole] were significantly increased with decreasing renal function from 9.2 h and 2.3, respectively, in healthy volunteers to 34 h and 6.7, respectively, in patients with total renal failure. The degree of accumulation of this metabolite on repeated dosing is probably of limited clinical significance in all patients except those with severe or total renal failure for reasons detailed in the text. 5 The elimination half-life and predicted accumulation on three times daily dosing of metabolite II, [2-methyl-5-nitroimidazole-l-acetic acid] increased rapidly with decreasing renal function. The average steady-state concentrations predicted for a dosing regimen of metronidazole (500 mg) every 8 h were 0.83 ,ug/ml and 17 ,ug/ml in patients with moderate and severe renal insufficiency, respectively. 6 In patients with creatinine clearances greater than 10 ml/min, the accumulation of metronidazole or its two major oxidative metabolites is unlikely to have any toxicological implications. Patients with creatinine clearances of less than 10 ml/min and not receiving dialysis will show marked accumulation of both metabolites on repeated dosing. Removal of these metabolites is achieved during haemodialysis.

“…It has been assumed that this advantage is caused by the high lipid/water partition coefficient and the long elimination half-life of tinidazole (Charuel et al, 1981;Houghton et al, 1982). Here the serum concentrations of either drug were equal to concentrations previously reported (Jokipii et al, 1977;Charuel et al, 1981;Houghton et (Amon & Amon, 1980). Exact comparisons are nevertheless difficult because of differences in drug dosage, route of administration and analytical method.…”

Section: Discussionmentioning

confidence: 87%

Placental transfer of metronidazole and tinidazole in early human pregnancy after a single infusion.

Karhunen¹

1984

1Concentrations of metronidazole and tinidazole were analysed in mother's serum, placental tissue and foetal tissue after a single intravenous infusion of 500 mg of either drug in 21 patients who underwent a first trimester legal abortion. 2 At the time of the evacuation (60 min from the start of the infusion) the concentrations of metronidazole and tinidazole in serum were 13.6 + 0.6 jxg/ml and 13.2 + 0.4 ,ug/ml, respectively. 3 In foetal tissue the concentrations of metronidazole and tinidazole reached 66% and 58%, and in placental tissue 26% and 37%, of the respective serum values.