Download secnidazole

SECNIDAZOLE
DRUGDEX® Evaluations
OVERVIEW
1) Class
a) This drug is a member of the following class(es):
Nitroimidazole
2) Contraindications
a) Hypersensitivity to secnidazole
DOSING INFORMATION
Drug Properties
A) Information on specific products and dosage forms can be obtained by referring to the
Tradename List (Product Index)
B) Synonyms
Secnidazole
Adult Dosage
Normal Dosage
Oral route
1) The optimal dose of secnidazole in INTESTINAL AMEBIASIS, GIARDIASIS,
VAGINAL TRICHOMONIASIS, and BACTERIAL VAGINOSIS appears to be 2
grams orally as a single administration
[1]
[6]
[4]
.
2) All family and institutional contacts of patients with giardiasis should also be
treated, as should male partners of women with vaginal trichomoniasis
[1]
.
3) Optimal doses of secnidazole in HEPATIC AMEBIASIS are unclear. However,
a dose of 1.5 gram orally as a single daily dose for 5 days has been
recommended
[1]
.
4) Gastrointestinal adverse effects were less when secnidazole was taken in the
evening compared to in the morning in vaginal trichomoniasis patients in one
study
[1]
.
5) Alcohol should be avoided for at least 24 hours after treatment with single
doses of secnidazole to avoid a disulfiram-like reaction
[1]
.
Pediatric Dosage
Normal Dosage
Oral route
1) The optimal dose of secnidazole in INTESTINAL AMEBIASIS and GIARDIASIS
in children appears to be 30 milligrams/kilogram orally as a single administration
[1]
[9]
[5]
. All family and institutional contacts of children with giardiasis should also be
treated
[1]
.
2) In children with established HEPATIC AMEBIASIS, secnidazole 30
milligrams/kilogram as a single daily dose for 5 days is recommended
[1]
.
PHARMACOKINETICS
Drug Concentration Levels
A) Time to Peak Concentration
1) Oral: 1.5 to 3 hours
[17]
[18]
a) Following single oral doses of secnidazole 2 g to healthy subjects, peak plasma
concentrations ranged from 36 to 46 mcg/mL
[17]
[18]
.
b) After 2-g oral doses, plasma secnidazole concentrations fall slowly, reaching approximately
10 mcg/mL in 48 hours and 4 mcg/mL in 72 hours
[18]
.
ADME
Absorption
A) Bioavailability
1) Near 100%
[17]
a) Secnidazole is well-absorbed after oral doses in healthy subjects
[17]
. However, absorption characteristics have not been studied in patients with diarrhea
(eg, intestinal amebiasis).
Distribution
A) Distribution Sites
1) Protein Binding
a) 15%
[17]
2) OTHER DISTRIBUTION SITES
a) Gingival crevicular fluid, good
1) Secnidazole achieves high concentrations in gingival crevicular fluid (only slightly
lower than corresponding plasma levels)
[18]
.
B) Distribution Kinetics
1) Volume of Distribution
a) 50 L
[17]
Metabolism
A) Metabolism Sites and Kinetics
1) Liver
a) Similar to metronidazole, secnidazole is metabolized in the liver, primarily via
oxidation. The drug does not induce or inhibit cytochrome P 450 isoenzymes
[17]
.
B) Metabolites
1) RP-35843, inactive
[17]
a) This major metabolite is formed via oxidation of secnidazole
[17]
.
2) Hydroxymethyl metabolites
[17]
Excretion
A) Kidney
1) Renal Excretion (%)
a) 10% to 50%, unchanged compound and metabolites
[17]
1) This suggests significant nonrenal clearance (eg, bile). Urinary excretion rates have
been higher in women.
B) Total Body Clearance
1) 1.7 L/hour
[17]
Elimination Half-life
A) Parent Compound
1) ELIMINATION HALF-LIFE
a) 17 to 29 hours (men)
[17]
[18]
[19]
[20]
; 14 hours (women)
[17]
1) These values are longer than those reported for metronidazole, tinidazole, and
ornidazole
[17]
[21]
[20]
.
2) The half-life of secnidazole has tended to be shorter in women than in men, due to
more rapid excretion in women
[17]
[20]
. In one study, plasma half-lives were 14 hours and 20 hours in women and men,
respectively (mean, 17 hours)
[17]
. However, this alteration does not necessitate dosage adjustment.
CAUTIONS
Contraindications
A) Hypersensitivity to secnidazole
Precautions
A) Hypersensitivity phenomena during therapy with other 5-nitroimidazole compounds, such as
ornidazole, metronidazole, or tinidazole (potential for cross-sensitivity)
B) Central nervous system disorders (dizziness/vertigo and ataxia have been observed with
secnidazole)
C) Renal or hepatic impairment (secnidazole has caused elevations in urea nitrogen; the
pharmacokinetics of the drug in these patients, and potential need for dose adjustment, have
not been studied)
D) Blood dyscrasias (potential for hematologic abnormalities during secnidazole therapy,
similar to metronidazole; however, these have been minimal in available secnidazole studies)
E) Concurrent use with warfarin (hypoprothrombinemic effects may be potentiated by
secnidazole (Gillis & Wiseman, 1996))
F) Concurrent use with alcohol (potential for disulfiram-like reaction, similar to metronidazole;
consumption of alcohol should be avoided for at least 24 hours posttreatment with single doses
(Gillis & Wiseman, 1996))
G) Concurrent use with disulfiram (Antabuse(R)) (potential for delirium or confusion (Gillis &
Wiseman, 1996))
Adverse Reactions
Dermatologic Effects
Dermatological finding
1) Erythema, PRURITUS, BLEPHAREDEMA, and URTICARIAL RASHES are
uncommon adverse effects that have been associated with oral secnidazole
[11]
.
Gastrointestinal Effects
Gastrointestinal tract finding
1) NAUSEA, VOMITING, EPIGASTRIC PAIN, ANOREXIA, metallic or bitter taste,
and glossitis are relatively frequent adverse effects of secnidazole, occurring in 2
to 29% of adults or children after single oral doses
[12]
[14]
[11]
[15]
. These effects are usually mild, not requiring drug discontinuation; however,
withdrawal of therapy has been required in some patients due to nausea,
anorexia, or a bitter taste
[11]
.
2) Secnidazole was better tolerated when taken in the evening compared to in the
morning in vaginal trichomoniasis patients in one study
[11]
.
3) The incidence and severity of gastrointestinal effects with secnidazole have
been generally similar to that reported for oral metronidazole and oral tinidazole in
comparative studies
[15]
[11]
.
Hematologic Effects
Hematology finding
1) EOSINOPHILIA and LEUKOCYTOSIS have occurred occasionally in patients
treated with oral secnidazole
[11]
. These changes do not appear to be clinically significant. LEUKOPENIA has not
been reported in available studies.
Neurologic Effects
Central nervous system finding
1) HEADACHE, DIZZINESS and VERTIGO have occurred in 2 to 12% in patients
treated with secnidazole
[12]
[13]
[11]
. Rarely, PARESTHESIAS and ATAXIA have been observed
[11]
. The incidence of these effects is similar to those reported for metronidazole and
tinidazole
[11]
.
Renal Effects
Urogenital finding
1) Significant elevations of blood urea nitrogen (BUN) have been described
occasionally in chronic amebiasis patients treated with secnidazole
[16]
. Changes in serum creatinine have not been reported, and it is unclear if BUN
alterations are related to fluid balance (ie, dehydration) or secnidazole.
CLINICAL APPLICATIONS
Monitoring Parameters
A) Therapeutic
1) Laboratory Parameters
a) Amebiasis or giardiasis: detection of E histolytica or G lamblia (trophozoites or cyst forms)
via endoscopy or by fecal samples during and after treatment
b) Urogenital trichomoniasis: microbiological analysis of vaginal secretions (T vaginalis)
c) Bacterial vaginosis: presence of clue cells in vaginal smear; potassium hydroxide (10%)
testing (amine odor in addition to vaginal discharge)
2) Physical Findings
a) Resolution of clinical signs/symptoms (eg, diarrhea, cramping, and flatulence in giardiasis
and intestinal amebiasis; dysuria, pain, and vaginal discharge in trichomoniasis)
B) Toxic
1) Laboratory Parameters
a) Laboratory monitoring is not required for the majority of patients treated
b) Complete blood counts are suggested in patients with prior hematologic disorders, and urea
nitrogen/serum creatinine in those with preexisting renal impairment
2) Physical Findings
a) Signs or symptoms of adverse effects, such as rash, dizziness, persistent nausea
Place In Therapy
A) The longer elimination half-life of secnidazole is the only apparent advantage of this agent
over other 5-nitroimidazole derivatives used in protozoal and bacterial infections, such as
metronidazole, tinidazole, and ornidazole. As secnidazole is primarily indicated for single-dose
administration, its place in therapy should be evaluated in this context. As such, available
clinical data suggest that the main place of one-dose secnidazole is as an alternative to
multiple-dose metronidazole for treatment of mild or moderate intestinal amebiasis, particularly
in rural endemic regions lacking extensive medical facilities and follow-up capability. However,
single-dose metronidazole has shown some degree of efficacy in this setting, and if welldesigned/controlled comparisons with single-dose secnidazole suggest comparable efficacy of
these regimens, metronidazole may be preferred based on cost
[22]
.
B) For other infections in which secnidazole has shown efficacy, the drug does not appear to
offer a significant advantage over single-dose regimens of other 5-nitroimidazoles, and may be
more costly. Specifically, single-dose tinidazole or metronidazole are highly effective in
giardiasis, urogenital trichomoniasis, and bacterial vaginosis; these regimens are considered
therapy of choice by most infectious disease specialists, and data are insufficient at present to
suggest a preference for secnidazole. However, direct comparisons are limited.
C) In the treatment of hepatic amebiasis, data are too limited to recommend secnidazole over
multiple-dose regimens of metronidazole or tinidazole, which are agents of choice.
D) Secnidazole has not been evaluated in the treatment of systemic anaerobic infections.
Mechanism of Action / Pharmacology
A) MECHANISM OF ACTION
1) Secnidazole is a 5-nitroimidazole antiprotozoal/antimicrobial agent structurally similar to
metronidazole and with similar actions and uses
[21]
[19]
. Secnidazole has a significantly longer elimination half-life (at least 20 hours) than
metronidazole (about 8 hours)
[17]
, which may constitute its primary clinical difference.
2) The in vitro antiprotozoal spectrum of secnidazole is generally comparable to that of
metronidazole, and includes Trichomonas vaginalis, T foetus, Entamoeba histolytica, and
Giardia lamblia (G duodenalis, G intestinalis)
[21]
[17]
. Activity in terms of minimum inhibitory concentration (MIC) is similar to that of metronidazole
for T vaginalis (0.7 mcg/mL); against E histolytica, minimum amebostatic concentrations of
these agents have also been similar (6 mcg/mL)
[17]
[20]
. Significantly lower concentrations of secnidazole (0.2 mcg/mL) have been required to inhibit G
duodenalis (G lamblia) compared to metronidazole (1.2 mcg/mL)
[17]
, although this is of questionable clinical relevance.
3) Like metronidazole, secnidazole demonstrates in vitro activity against anaerobes, including
Bacteroides fragilis and other Bacteroides spp, Clostridium spp, Peptococcus spp, and
Peptostreptococcus spp
[21]
. In vitro MIC values against B fragilis are nearly identical for secnidazole and metronidazole
(0.4 to 1 mcg/mL), whereas another 5-nitroimidazole, tinidazole, has been more active (0.1
mcg/mL)
[19]
[17]
.
B) REVIEW ARTICLES
1) The pharmacology, pharmacokinetics, adverse effects, and therapeutic use of secnidazole in
protozoal infections and bacterial vaginitis have been reviewed
[17]
.
Therapeutic Uses
Amebic infection
1) Overview
FDA Approval: Adult, no; Pediatric, no
Efficacy: Adult, Evidence favors efficacy
Recommendation: Adult, Class IIb
Strength of Evidence: Adult, Category B
See Drug Consult reference:
RECOMMENDATION AND EVIDENCE RATINGS
2) Summary:
Single oral doses effective
Similar efficacy in adults and children
3) Adult:
a) Single oral doses of secnidazole have produced clinical cure and parasitological
eradication in 80 to 100% of adults and children with INTESTINAL AMEBIASIS, mostly
of mild or moderate severity
[1]
[2]
[3]
[4]
[5]
[6]
. Effective doses in these studies were 2 grams in adults and 30 milligrams/kilogram in
children, and a decrease in symptoms with eradication of E histolytica was observed in
most patients within one week of treatment.
b) The efficacy of secnidazole has been similar in children and adults
[1]
and in chronic versus acute amebiasis
[1]
[4]
[7]
. The drug has compared well with single-dose or multiple-dose regimens of
metronidazole
[1]
[5]
.
c) Secnidazole 1.5 or 2 grams daily for up to one week appeared effective in patients
with HEPATIC AMEBIASIS, although confirmation of parasitological cure was not
provided
[1]
.
Bacterial vaginosis
1) Overview
FDA Approval: Adult, no; Pediatric, no
Efficacy: Adult, Evidence favors efficacy
Recommendation: Adult, Class IIb
Strength of Evidence: Adult, Category B
See Drug Consult reference:
RECOMMENDATION AND EVIDENCE RATINGS
2) Summary:
Not the agent of choice
3) Adult:
a) Bacterial vaginosis is usually a polymicrobial infection, associated with the presence
of Gardnerella vaginalis, anaerobes, and Mobiluncus spp. The current agent is choice is
metronidazole, even though this agent may not be active against G vaginalis in vitro.
Oral clindamycin has also been effective
[8]
[1]
.
b) Oral secnidazole in 2-gram single doses has produced clinical cure or improvement in
approximately 80% of bacterial vaginosis patients (range, 70 to 90%), with
microbiological cure (based primarily on potassium hydroxide testing and absence of
clue cells on vaginal smears) occurring in 81 to 93%. Clinical relapse has been reported
in about 5% of patients
[1]
.
c) In direct comparisons with 7-day courses of metronidazole (800 milligrams daily),
single-dose secnidazole has been at least as effective
[1]
. In other studies, single-dose metronidazole has also proven efficacious, with overall
cure rates similar those of single-dose secnidazole (about 85%)
[1]
.
Giardiasis
1) Overview
FDA Approval: Adult, no; Pediatric, no
Efficacy: Adult, Evidence favors efficacy; Pediatric, Evidence favors efficacy
Recommendation: Adult, Class IIb; Pediatric, Class IIb
Strength of Evidence: Adult, Category B; Pediatric, Category B
See Drug Consult reference:
RECOMMENDATION AND EVIDENCE RATINGS
2) Summary:
Similar to metronidazole in efficacy
3) Adult:
a) One day of treatment with secnidazole (either 30 milligrams/kilogram as a single dose
or in two divided doses on the same day) has demonstrated efficacy in the therapy of
giardiasis in adults and children. Parasitological and clinical cure rates of 92 to 100%
and 86 to 100%, respectively, have been reported
[1]
[9]
.
b) Clinical/parasitological cure rates have not differed significantly between single-dose
secnidazole and 5-, 7-, or 10-day courses of metronidazole in these patients
[1]
[9]
.
4) Pediatric:
a) A single dose of secnidazole provided effective parasite eradication coupled with a
significant improvement in serum hemoglobin levels, in an open-labeled, controlled
clinical study of children with giardiasis. Fifty-seven children with depressed hemoglobin
levels (below 12 grams/deciliter (g/dL)) related to Giardia intestinalis infection received a
single oral dose of secnidazole suspension 30 milligrams/kilogram. Parasitological
clearance occurred in 95% of treated patients. Children exhibiting abnormally low serum
hemoglobin (mean of 11.6 g/dL) exhibited a significant increase in hemoglobin
concentration 15 days after treatment, to a mean of 12.4 g/dL (p less than 0.05). There
were no adverse events observed
[10]
.
Trichomoniasis
1) Overview
FDA Approval: Adult, no; Pediatric, no
Efficacy: Adult, Evidence favors efficacy
Recommendation: Adult, Class IIb
Strength of Evidence: Adult, Category B
See Drug Consult reference:
RECOMMENDATION AND EVIDENCE RATINGS
2) Summary:
Up to 100% parasitological cure has been seen 3 weeks posttreatment, and clinical
relapse has been rare
3) Adult:
a) Oral secnidazole in single 2-gram doses has produced parasitological eradication in
approximately 95% of men and women with UROGENITAL TRICHOMONIASIS, with
most patients achieving this endpoint within 3 days of treatment. Rates of clinical cure
(eg, resolution of vaginal/urethral discharge, dysuria) have been approximately 95% in
women and ranged from 60 to 100% in men (Gillis & Wiseman, 1996; Ozbilgin et al,
1994.
b) A secnidazole regimen of 0.5 gram twice daily for 4 days (total, 4 grams) offered no
advantage over a single 2-gram dose in one trial
[1]
.
c) Cross-comparisons of studies using single-dose metronidazole (2 grams) or tinidazole
(2 grams) in urogenital trichomoniasis
[1]
reveal response rates similar to those observed with 2-gram single doses of
secnidazole. However, direct comparisons are lacking.
Comparative Efficacy / Evaluation With Other Therapies
Metronidazole
Amebic infection
a) A single dose of secnidazole 30 mg/kg has been comparable in efficacy to
single-dose metronidazole 50 mg/kg in children with intestinal amebiasis
[24]
. Clinical and parasitological cure was achieved in over 95% of patients. However,
this study was small (n=28), and results were reported only on the basis of
nutritional status. Further comparisons of these single-dose regimens are needed.
Bacterial vaginosis
a) Single doses of secnidazole 2 g have produced parasitological/clinical
response rates similar to or greater than those observed with 7-day courses of
metronidazole (800 mg daily) in direct (nonblinded) comparisons in bacterial
vaginitis patients
[25]
.
b) Any combination of orally plus vaginally administered treatment was more
effective than any single agent given orally alone or vaginally alone when
ornidazole, secnidazole, and metronidazole were compared in an open trial
involving 152 Turkish women with non-specific vaginitis. Eight different treatment
regimens were compared: -1- Ornidazole oral 2x500-mg daily for 5 days -2Ornidazole vaginal 500-mg daily for 5 days -3- Ornidazole oral plus vaginal -4Secnidazole oral 4x500-mg single dose -5- Secnidazole oral (single dose) plus
ornidazole vaginal 500-mg daily for 5 days -6- Secnidazole oral (single dose) plus
metronidazole vaginal 2x500-mg daily for 7 days -7- Ornidazole oral plus
metronidazole vaginal -8- Metronidazole vaginal Partners were not treated.
Patients were free from trichomoniasis or candidiasis. Follow-up was scheduled
for between 30 to 40 days following treatment. Cure was defined as freedom from
symptoms and vaginal discharge, and negative clue cells. Results were
summarized Saracoglu et al, 1998):
TREATMENT
GROUP
Patients
(number)
Cure
Recurrence
n
(%)
n
(%)
1
34
32
94%
2
6%
2
21
16
76%
5
24%
3**
14
14
100%
4
29
21
72%
8
28%
5**
10
9
90%
1
10%
6**
11
11
100%
7**
10
9
90%
1
10%
8
23
20
87%
3
13%
** = regimens with both oral plus vaginal dosing
Giardiasis
a) In children with giardiasis, clinical/parasitological cure rates have not differed
significantly between single-dose secnidazole 30 mg/kg (one dose or two divided
doses) and a 7- or 10-day course of metronidazole 20 mg/kg/day
[26]
[25]
. Similarly, a single dose of secnidazole (30 mg/kg, approximately 2 g) produced
parasitological/clinical cure rates comparable to metronidazole 0.5 g daily for 5
days in adult patients
[25]
; a trend toward the superiority of secnidazole for clinical cure was observed (86%
versus 73%).
Ornidazole
Amebic infection
a) Secnidazole 30 milligrams (mg)/kilogram (kg) daily for 3 days was slightly less
effective than ornidazole 15 mg/kg twice daily for 10 days in the treatment of
children with symptomatic intestinal amebiasis in one poorly designed study
[27]
.
Bacterial vaginosis
a) Any combination of orally plus vaginally administered treatment was more
effective than any single agent given orally alone or vaginally alone when
ornidazole, secnidazole, and metronidazole were compared in an open trial
involving 152 Turkish women with non-specific vaginitis. Eight different treatment
regimens were compared: -1- Ornidazole oral 2x500-mg daily for 5 days -2Ornidazole vaginal 500-mg daily for 5 days -3- Ornidazole oral plus vaginal -4Secnidazole oral 4x500-mg single dose -5- Secnidazole oral (single dose) plus
ornidazole vaginal 500-mg daily for 5 days -6- Secnidazole oral (single dose) plus
metronidazole vaginal 2x500-mg daily for 7 days -7- Ornidazole oral plus
metronidazole vaginal -8- Metronidazole vaginal Partners were not treated.
Patients were free from trichomoniasis or candidiasis. Follow-up was scheduled
for between 30 to 40 days following treatment. Cure was defined as freedom from
symptoms and vaginal discharge, and negative clue cells. Results were
summarized Saracoglu et al, 1998):
TREATMENT
GROUP
Patients
(number)
Cure
Recurrence
n
(%)
n
(%)
1
34
32
94%
2
6%
2
21
16
76%
5
24%
3**
14
14
100%
4
29
21
72%
8
28%
5**
10
9
90%
1
10%
6**
11
11
100%
7**
10
9
90%
1
10%
8
23
20
87%
3
13%
** = regimens with both oral plus vaginal dosing
Tetracycline
Amebic infection
a) A 5-day regimen of oral tetracycline plus clioquinol has been inferior to single
doses of oral secnidazole (2 g) in treating intestinal amebiasis. Clinical cure rates
were lower with the tetracycline regimen, and occurred significantly later
compared to secnidazole. In one study, cure rates on day 4 were 7% and 80% in
patients treated with tetracycline/clioquinol and secnidazole, respectively
[23]
.
Tinidazole
Amebic infection
a) Single-dose secnidazole (2 grams (g)) and a 2-day course of tinidazole (2
g/day) were equally effective in the treatment of intestinal amebiasis in one trial
[28]
.
Bacterial vaginosis
a) Tinidazole and secnidazole, each in 2-gram single oral doses, produced nearly
identical clinical cure/improvement rates (88% and 90%, respectively) and
microbiological cure rates (about 80%) in a double-blind study involving women
with bacterial vaginitis
[28]
.
REFERENCES
1. Gillis JC & Wiseman LR: Secnidazole: a review of its antimicrobial activity, pharmacokinetic
properties and therapeutic use in the management of protozoal infections and bacterial vaginosis.
Drugs 1996; 51:621-638.
2. Omrani G, Rastegar-Lari A, & Khamseh M: Effect of single dose of secnidazole in treatment of
intestinal amoebiasis. J Pakistan Medical Association 1995; 45:159.
3. Qureshi H, Baqai R, Zuberi SJ, et al: Efficacy of secnidazole in the treatment of intestinal
amoebiasis. J Pakistan Medical Association 1994; 44:93-94.
4. Latonio AA: Efficacy of a single dose of secnidazole in the treatment of acute and chronic
amoebiasis. J Trop Med Hygiene 1988; 91:202-204.
5. Sinuhaji AB, Lubis CP, Daulay HRM, et al: A double blind trial between metronidazole and
secnidazole in acute amebic dysentery in children (preliminary report). Paediatrica Indonesiana 1986;
26:9-14.
6. Soedin K, Syukran OKA, Fadillah A, et al: Comparison between the efficacy of a single dose of
secnidazole with a 5-day course of tetracycline and clioquinol in the treatment of acute intestinal
amoebiasis. Pharmatherapeutica 1985; 4:251-254.
7. Rossignol JF, Maisonneuve H, & Cho YW: Nitroimidazoles in the treatment of trichomoniasis,
giardiasis, and amebiasis. Int J Clin Pharmacol Ther Toxicol 1984; 22:63-72.
8. Anon: The choice of antibacterial drugs. Med Lett Drug Ther 1996; 38:25-33.
9. Rastegar-Lari A & Salek-Moghaddam A: Single-dose secnidazole versus 10-day metronidazole
therapy of giardiasis in Iranian children. J Tropical Pediatrics 1996; 42:184.
10. Jimenez JC, Rodriguez N, Di Prisco MC, et al: Haemoglobin concentrations and infection by
Giardia intestinalis in children: effect of treatment with secnidazole. Ann Trop Med Parasitol 1999;
93(8):823-827.
11. Gillis JC & Wiseman LR: Secnidazole: a review of its antimicrobial activity, pharmacokinetic
properties and therapeutic use in the management of protozoal infections and bacterial vaginosis.
Drugs 1996; 51:621-638.
12. Rossignol JF, Maisonneuve H, & Cho YW: Nitroimidazoles in the treatment of trichomoniasis,
giardiasis, and amebiasis. Int J Clin Pharmacol Ther Toxicol 1984; 22:63-72.
13. Qureshi H, Baqai R, Zuberi SJ, et al: Efficacy of secnidazole in the treatment of intestinal
amoebiasis. J Pakistan Medical Association 1994; 44:93-94.
14. Videau D, Niel G, Siboulet A, et al: Secnidazole: a 5-nitroimidazole derivative with a long half-life.
Br J Venereal Diseases 1978; 54:77-80.
15. Rastegar-Lari A & Salek-Moghaddam A: Single-dose secnidazole versus 10-day metronidazole
therapy of giardiasis in Iranian children. J Tropical Pediatrics 1996; 42:184.
16. Latonio AA: Efficacy of a single dose of secnidazole in the treatment of acute and chronic
amoebiasis. J Trop Med Hygiene 1988; 91:202-204.
17. Gillis JC & Wiseman LR: Secnidazole: a review of its antimicrobial activity, pharmacokinetic
properties and therapeutic use in the management of protozoal infections and bacterial vaginosis.
Drugs 1996; 51:621-638.
18. Tenenbaum H, Cuisinier FHG, Le Liboux, et al: Secnidazole concentrations in plasma and
crevicular fluid after a single oral dose. J Clin Periodontol 1993; 20:505-508.
19. Symonds J: Secnidazole - a nitroimidazole with a prolonged serum half-life. J Antimicrob
Chemother 1979; 5:484-486.
20. Videau D, Niel G, Siboulet A, et al: Secnidazole: a 5-nitroimidazole derivative with a long half-life.
Br J Venereal Diseases 1978; 54:77-80.
21. Rossignol JF, Maisonneuve H, & Cho YW: Nitroimidazoles in the treatment of trichomoniasis,
giardiasis, and amebiasis. Int J Clin Pharmacol Ther Toxicol 1984; 22:63-72.
22. Toppare MF, Kitapci F, Senses DA, et al: Ornidazole and secnidazole in the treatment of
symptomatic intestinal amoebiasis in childhood. Tropical Doctor 1994; 24:183-184.
23. Gillis JC & Wiseman LR: Secnidazole: a review of its antimicrobial activity, pharmacokinetic
properties and therapeutic use in the management of protozoal infections and bacterial vaginosis.
Drugs 1996; 51:621-638.
24. Sinuhaji AB, Lubis CP, Daulay HRM, et al: A double blind trial between metronidazole and
secnidazole in acute amebic dysentery in children (preliminary report). Paediatrica Indonesiana 1986;
26:9-14.
25. Gillis JC & Wiseman LR: Secnidazole: a review of its antimicrobial activity, pharmacokinetic
properties and therapeutic use in the management of protozoal infections and bacterial vaginosis.
Drugs 1996; 51:621-638.
26. Rastegar-Lari A & Salek-Moghaddam A: Single-dose secnidazole versus 10-day metronidazole
therapy of giardiasis in Iranian children. J Trop Pediatr 1996; 42:184-185.
27. Toppare MF, Kitapci F, Senses DA, et al: Ornidazole and secnidazole in the treatment of
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