Absorption and Excretion of Metronidazole. Part I: Serum Concentration and Urinary Excretion after Oral Administration

Kane, P. O.; McFadzean, James A.; Squires, S.; King, A. J.; Nicol, C. S.

doi:10.1136/sti.37.4.273

Cited by 32 publications

(22 citation statements)

References 1 publication

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In general, peak blood levels as determined by bioassay with single 250-and 500-mg doses are in the same range as those reported previously with chemical methods (5,16,17), i.e., 5 to 6 jg/ml and 10 to 12 ,g/ml, respectively. As in most previous studies, the rate of absorption was quite variable in our volunteers, with high blood levels occurring in some within 15 min after ingestion, and peaks as late as 2 to 4 h in others.…”

Section: Discussionsupporting

confidence: 67%

“…Metronidazole [1-(,-hydroxyethyl)-2-methyl-5-nitroimidazole], which has been used effectively for many years against certain protozoal infections, has been shown to be active against most anaerobic bacteria in vitro, and to be promising clinically in treating anaerobic infections (13). Except for one recent report (6), previous studies of blood and urine levels have relied upon nonbiological assay methods in which metronidazole and its metabolites are measured without regard to their antibacterial action (5,14,16). The present study was designed to measure biologically active metronidazole in the serum and urine after single and multiple doses and to determine its pharmacokinetics.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Pharmacokinetics of Metronidazole as Determined by Bioassay

Ralph

Clarke

Libke

et al. 1974

Antimicrob Agents Chemother

View full text Add to dashboard Cite

The pharmacokinetics of metronidazole, a drug effective in vitro against most anaerobic bacteria and promising in treating anaerobic infections, are described. Serum and urine levels after single and multiple doses in 10 adult male volunteers were measured by an agar well diffusion bioassay using clostridial species as the test organisms under anaerobic conditions. Peak serum levels averaged 11.5 ,ug/ml and 6.2 ug/ml after single 500-mg and 250-mg doses, respectively. Renal clearance was only 10.2 ml/min per 1.73 M2, and less than 20% of the administered dose was recovered in the urine as active drug in 24 h. The average serum half-life was 8.7 h, and there was no protein binding as determined by an ultrafiltration method. With multiple doses of metronidazole (500 mg four times a day and 250 mg three times a day), blood levels increased progressively for the first few doses and then leveled off, with no significant accumulation occurring between 3 and 7 days. On 250 mg three times a day, serum levels just before the 8 a.m. dose (12 h after the preceding dose) on the third day averaged 3.9 Mg/ml, and before the 8 p.m. dose, 5.7 Mg/ml. For the higher, 500-mg dose (four times a day) regimen, the corresponding minimum serum levels were 13.1 Mig/ml at 8 a.m. and 21.3 Mg/ml at 8 p.m. Peak levels would have been about 10 ,g/ml higher, and since the minimum inhibitory concentrations of most anaerobes including Bacteroides fragilis are less than 6 Mg/ ml, these concentrations should be highly effective therapeutically, even for severe infections.With the increasing awareness of the pathogenicity of anaerobic bacteria, antimicrobial agents which were effective against these organisms are receiving greater attention. Metronidazole [1-(,-hydroxyethyl)-2-methyl-5-nitroimidazole], which has been used effectively for many years against certain protozoal infec-

show abstract

Section: Discussionsupporting

confidence: 67%

mentioning

confidence: 99%

Pharmacokinetics of Metronidazole as Determined by Bioassay

Ralph

Clarke

Libke

et al. 1974

Antimicrob Agents Chemother

View full text Add to dashboard Cite

show abstract

“…(6) = Six on 2 g. stat (TW"oodcock, 1972) (4) = Four on 400 mg. four times a day (Fig. 1) (2) = Two on 200 mg. three times a day (8 a.m. specimens) (Kane, McFadzean, Squires, King, and Nicol, 1961) (1) = One of the two above (12-hourly specimens) METRONIDAZOLE AND TETRACYCLINE Whilst the trial was being planned, Szanto (1971) suggested a possible antagonism between oxytetracycline and metronidazole. Four of the trial patients who were also taking tetracycline 500 mg. four times daily had blood specimens taken 36 hours after starting treatment.…”

Section: Resultsmentioning

confidence: 99%

Two-day treatment with metronidazole in vaginal trichomoniasis.

Woodcock¹

1972

Sexually Transmitted Infections

View full text Add to dashboard Cite

Recent studies have demonstrated that the traditional 7-day course of metronidazole at a dosage of 200 mg. three times a day is not the only schedule effective in trichomoniasis (McClean, 1971;Csonka, 1971;Woodcock, 1972). It was decided to assess the efficacy of metronidazole 400 mg. four times a day for 2 days; this dosage would facilitate its administration with tetracycline 500 mg. four times a day, a schedule sometimes used as an alternative to penicillin in the treatment of gonorrhoea. MethodsThe patients taking part in the trial were attending the St. Mary's Hospital Special Clinic, and were diagnosed by routine darkfield microscopy of the vaginal secretion as having vaginal trichomoniasis. When cervical cytology was investigated this often confirmed the diagnosis, but it was not used as a diagnostic criterion nor as a test of cure. Cultural methods were not used because previous experience of their use in this clinic had shown them to be not substantially more reliable than simple microscopy; nor was any attempt made to diagnose trichomoniasis in the male consorts, many of whom were routinely Received for publication April 14, 1972 treated with metronidazole 200 mg. three times a day for 1 week.Patients were included in the trial whenever the diagnosis was made while the doctor conducting the trial was on duty. The only patients excluded were those who had already been treated for a trichomonal infection in the previous 3 months. The patients were asked to return in 1 week and again after 1 month for repeat tests; further visits were made at the discretion of the patient, but an interval of at least 3 months elapsed before the results for each patient were reviewed.The criteria for diagnosis and assessment of cure, although satisfactory for routine clinical work, might be judged inadequate for a scientific study. It was therefore decided to establish a control group of patients by the same criteria, and to treat them with the standard course of metronidazole 200 mg. three times a day for 7 days. The use of a control group made the difficult task of distinguishing between treatment failure and re-infection of less importance, as the results were to be judged relatively rather than in terms of absolute success or failure. The controls were patients in whom the diagnosis was made when the doctor conducting the trial was not on duty. MaterialThe preliminary data are shown in Tables I and II.

show abstract

“…Metronidazole is well absorbed from the gastrointestinal tract and ser.um levels up to 72.0 Ag/ml have been achieved with oral therapy (6,9). The compound diffuses into all tissues with therapeutic levels achieved in abscesses, bile, (17).…”

Section: Resultsmentioning

confidence: 99%

Treatment of Anaerobic Infections with Metronidazole

Tally

Sutter²,

Finegold³

1975

Antimicrob Agents Chemother

122

View full text Add to dashboard Cite

The results of treatment of 10 patients with anaerobic infections with metronidazole are presented. Six patients were cured, three showed initial good response but circumstances required a change to another drug, and one patient did not respond. The unique spectrum of the drug, its pharmacology, and limitations are discussed. The results indicate that further clinical trials to determine the efficacy of metronidazole in the treatment of anerobic infections are indicated.

show abstract

Absorption and Excretion of Metronidazole. Part I: Serum Concentration and Urinary Excretion after Oral Administration

Cited by 32 publications

References 1 publication

Pharmacokinetics of Metronidazole as Determined by Bioassay

Pharmacokinetics of Metronidazole as Determined by Bioassay

Two-day treatment with metronidazole in vaginal trichomoniasis.

Treatment of Anaerobic Infections with Metronidazole

Contact Info

Product

Resources

About