Ornidazole induced Stevens-Johnson syndrome without body surface involved: A case report.

RATIONALE: Ornidazole is a synthetic nitroimidazole derivative that is commonly prescribed for antiparasitic or anti-anaerobic infections. It is generally well tolerated, with known side effects including gastrointestinal tract, anaphylaxis, and central nervous system reactions. Ornidazole-induced binocular reactive keratitis and several mucocutaneous lesions have been rarely reported. PATIENT CONCERNS: A 52-year-old woman who suffered from vaginitis and received an ornidazole vaginal plug (0.5 g). Approximately 20 minutes after the suppository was inserted into the vagina, her lips were swollen and valva and labia were burning. Her eyes were red, sore, and watery. DIAGNOSIS: She was diagnosed as Steven-Johnson syndrome by the ophthalmologist. According to the Naranjo scale, the adverse drug reaction was evaluated to be probable and severe. INTERVENTIONS: Dexamethasone was intravenous administrated as anti-inflammatory therapy for 10 days. Eye drops were locally given to relieve edema and promote healing of the epithelium. The symptoms of her eyes, lips, vulva and crissum were soon relieved. OUTCOMES: The patient was discharge from hospital with improved symptoms. LESSONS: In order to avoid severe adverse effect, the patient should not use metronidazole ether orally or vaginally. The case emphasized the importance of rapid and accurate diagnosis of Steven-Johnson syndrome induced by ornidazole vaginal plug, especially when the eye symptoms were the chief complaint without body skin involved.

Pharmacokinetics and safety of injected ornidazole compared to its enantiomer levornidazole in healthy Chinese subjects.

OBJECTIVE: To compare the pharmacokinetics of levornidazole and ornidazole in healthy Chinese subjects after a single intravenous injection, and to determine whether the chiral inversion of levornidazole occurs in vivo. MATERIALS AND METHODS: The study was a randomized, open-label, two-period crossover, single-dose design. A total of 12 subjects were enrolled in this study. Subjects received an intravenous injection of either levornidazole sodium chloride injection (200 mL: 0.5 g) or ornidazole sodium chloride injection (200 mL: 0.5 g) once per period. The plasma concentrations of levornidazole, ornidazole, and their metabolites were measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. Phenix WinNolin software (version 6.4) was used to calculate the pharmacokinetic parameters of levornidazole, ornidazole, and their metabolites. RESULTS: Dexornidazole was not detected in the plasma or urine. After a single intravenous injection of levornidazole or ornidazole, there was no significant difference in Cmax between the two drugs (p < 0.05). The AUC0-∞ and AUC0-t of levornidazole were slightly lower than those of ornidazole. Metabolites M1 and M4 were detected in the plasma of both drugs, and their pharmacokinetic parameters were similar. Metabolites M1, M2, and M4 were present in urine. The average cumulative urinary excretion rates of levornidazole and its metabolites M1 and M4 were: during 0 - 24 hours (8.14 ± 0.80%, 0.560 ± 0.072%, and 1.42 ± 0.19%) and 0 - 60 hours (10.5 ± 1.0%, 0.960 ± 0.084%, and 2.52 ± 0.20%), the average cumulative urinary excretion rates of ornidazole and its metabolites M1 and M4 were: 0 - 24 hours (8.64 ± 0.98%, 0.486 ± 0.074%, and 1.46 ± 0.21%), 0 - 60 hours (11.8 ± 1.0%, 0.888 ± 0.070%, and 2.76 ± 0.20%). The incidence of adverse reactions was similar between the two drugs. CONCLUSION: No chiral inversion of levornidazole occurred in vivo after intravenous administration of levornidazole. The pharmacokinetic parameters and cumulative excretion rates of levornidazole and ornidazole were similar. The safety results were basically consistent between the two drugs.

Effect of moxa smoke on sperm parameters and oxidative stress in rats with asthenozoospermia.

Asthenozoospermia is a leading cause of male infertility, characterized by reduced sperm motility. In this study, we determined sperm motility and the activities of antioxidant enzymes and oxidation products in the testis of rats with ornidazole (ORN)-induced asthenozoospermia and further examined and compared the differential effects of moxa smoke (MS) and cigarette smoke (CS) on sperm motility and oxidative stress (OS) of asthenozoospermic rats. The smoke intervention was initiated 11 days after intragastric administration of ORN, followed by the examination of testis index, sperm parameters, OS-related gene levels, and testicular histopathology. Sperm motility and antioxidant enzyme activities, as well as oxidation products significantly decreased in ORN-induced rats compared with MS-treated rats (p < .05-.001). MS treatment restored the reduced sperm motility and activities of glutathione peroxidase, superoxide dismutase, and catalase, but increased the malondialdehyde and nitric oxide synthetase levels in ORN-induced rats (p < .05-.001). Also, the histopathological changes in the testis of ORN-induced rats were improved by MS treatment. The study highlighted that MS was an effective factor in moxibustion therapy, which notably improved the sperm motility of asthenozoospermic rats by inhibiting OS in the reproductive system.

Clinical Symptoms and Quality of Life Improvement Value of Ornidazole Mixture in Auxiliary Filling Treatment of Patients with Endodontic Disease.

To evaluate the clinical effect of ornidazole mixture in auxiliary filling of patients with endodontic disease. A total of 124 patients with endodontic diseases admitted to our hospital from January 2020 to December 2021 were included and divided into two groups according to the random number table. The observation group (n = 62) was given ornidazole mixture-assisted filling, while the control group (n = 62) was given pulp mummification filling to evaluate its application effect. Compared with the control group, the disappearance time of tooth hyperesthesia, gingival redness, and pain symptoms in the observation group were significantly shorter and the difference had statistical significance (P < 0.05); the excellent and good rate of the observation group was 96.77% and 85.48%, respectively, and the difference had statistical significance (P < 0.05); the masticatory efficiency, occlusal force, and oral health-related quality of life scores in the observation group were higher than those in the control group after treatment, and the difference had statistical significance (P < 0.05). Ornidazole mixture can promote the curative effect, shorten the time of symptom disappearance, and effectively improve the masticatory function and quality of life in patients with endodontic diseases.

Runjing extract promotes spermatogenesis in rats with ornidazole-induced oligoasthenoteratozoospermia through extracellular signal-regulated kinase signalling, and regulating vimentin expression.

OBJECTIVE: To investigate the efficacy of Runjing (RJ) extract on oligoasthenoteratozoospermia (OAT) induced by ornidazole (ORN) in rats, and to study the underlying mechanism. METHODS: Twenty-four adult male Sprague-Dawley rats were treated with normal saline (control), ORN (OAT model), ORN + 4.725 g·kg－1·d－1 RJ extract (low-dose) and ORN+ 18.9 g·kg－1·d－1 RJ extract (high-dose) for 4 weeks. The rats were then euthanized and sperm and testis samples were collected for analysis. Sperm count, motility and morphology were calculated by sperm suspension from cauda epididymis. Testicular histopathological changes were analyzed by hematoxylin and eosin staining and TdT mediated dUTP nick end labelling. Moreover, the expression of vimentin and extracellular signal-regulated kinase (ERK) were examined through Western blot, and the distribution of vimentin was detected via immunohistochemistry. RESULTS: ORN successfully induces seminiferous epithelium injury, cellular apoptosis, and finally OAT (P < 0.05). However, both low-dose and highdose RJ extract partially rescues the phenotypes (P < 0.05). Moreover, the expressions of vimentin and ERK were significantly altered in ORN testes (all P < 0.001), while RJ extract partially reversed these effects (P < 0.01 or P < 0.001). CONCLUSION: RJ extract can help maintain spermatogenesis through ERK signalling, and regulating vimentin expression.

Design and Evaluation of Sustained Release of Ornidazole by Dental Inserts.

Aim & Background: Ornidazole is an antimicrobial drug used to treat certain types of vaginal, urinary tract, and interstitial infections. The study aims to formulate and evaluate the dental inserts by using a drug candidate to sustained drug release to improve patient compliance, reduce dosing frequency, reduce the risk of dose dumping, and avoid the first-pass metabolism. They have better therapeutic efficacy and fewer side effects. METHODS: The dental inserts were prepared using various polymers alone and in combination with the different ratios of polymers. The evaluation parameters like thickness, drug content, content uniformity, moisture reuptake, weight variation, swelling studies, and erosion studies of the optimized inserts were studied. The in-vivo studies were conducted to determine the reduction of pocket depth in human volunteers. RESULTS: The system containing ethylcellulose and hydroxyl methyl propyl cellulose K100M (4:1) formulation F6 was optimized because drug release was sustained up to 120 hrs concerning other formulations. Optimized formulation followed first-order kinetics and Peppas release kinetics via fickian diffusion. There was no swelling, itching, irritation, and no reduction in the pocket depth in in-vivo studies. CONCLUSION: The study concluded that dental inserts could extend the release of Ornidazole for many hours and also enhance bioavailability. Furthermore, they also help in avoiding the first-pass effect. In vivo studies' observations showed no itching, irritation, swelling, and pocket-depth reduction.

Diagnostic workup including CD203c-based basophil activation test in immediate hypersensitivity due to metronidazole and ornidazole and evaluation of cross-reactivity in between.

BACKGROUND: Little is known about the diagnostic approaches for immediate hypersensitivity reactions (IHRs) due to 5-nitroimidazole antibiotics. The aim was to evaluate the usefulness of in vivo tests and basophil activation test (BAT) for the diagnosis of IHRs due to metronidazole and ornidazole and to determine possible cross-reactivity in between. METHODS: Forty-nine patients with a clear history of IHRs due to these drugs and 20 healthy subjects who were known to tolerate these drugs were included. Skin tests (STs) and single-blind placebo-controlled drug provocation tests (SBPCDPTs) were performed with both drugs whereas BAT was applied only with the culprit drug. RESULTS: The most and least common reaction types were urticaria/angioedema (34.7%) and anaphylaxis (14.3%), respectively. SBPCDPTs were positive in 15 out of 47 patients, and only 7 had positive STs. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of STs for metronidazole/ornidazole were 33.3%/16.6%, 94.2%/97.3%, 60%/50%, and 84.6%/88.1%, respectively. BAT was positive in 12 out of 15 patients and negative in 10 control subjects, giving a sensitivity rate of 71.4% (CI, 29.0%-96.3%) for metronidazole and 83.3% (CI, 35.8%-99.5%) for ornidazole. The optimal concentration of both drugs for BAT was determined as 5 mg/mL. No cross-reactivity among two drugs was observed according to in vivo tests. CONCLUSIONS: Our study showed that SBPCDPT and BAT are both useful diagnostic tools for IHRs due to 5-nitroimidazole antibiotics and can be used as supplementary to each other. No cross-reactivity between metronidazole and ornidazole in IHRs exists.

Analysis of Ornidazole Injection in Clinical Use at Post-marketing Stage by Centralized Hospital Monitoring System.

This study aims to analyze the clinical use of ornidazole injection at the post-marketing stage by centralized hospital monitoring system method, and investigate its widespread use in patients, in order to regulate and guide the rational drug use, improve the drug specificity and provide a basis for drug therapy. The study adopts a prospective, multi-center, large sample size, centralized hospital monitoring system. We selected five leading hospitals in Hubei province, and observed the inpatients who received the ornidazole injection from July 1, 2015 to October 31, 2015. The basic information of patients was recorded, as well as the drug use and adverse events. The statistical analysis was performed based on these data. A total of 4396 individuals were enrolled in this study, most of them were middle-aged female patients and the ornidazole injection was mainly used as prophylactic prior to surgery to prevent the infections, and surgical treatment of anaerobic infections, abdominal infections and pelvic infections. The irrational drug use existed mainly in the prescribing and administration process, including unreasonable dosing frequency, rapid intravenous drip speed and extended duration of drug use. Eleven cases of adverse reactions were collected during the monitoring, incidence rate of adverse reactions was 2.5‰; adverse drug reactions occurred within 30 min. The study results fully reflected the usage of ornidazole injection in the real world. Based on the study, we calculated the adverse reaction incidence of ornidazole and identified the risk factors which may affect the safety of ornidazole injection. Study results strongly recommend that the manufacturers should publish standards for inpatient use and doctors should prescribe with caution accordingly.

Taurine Increases Spermatozoa Quality and Function in Asthenospermia Rats Impaired by Ornidazole.

Asthenospermia has been considered as one of the crucial causes of male infertility, which was closely related to epididymal dysfunction. Lots of documents have revealed that taurine palys an important role in male reproduction, including antioxidation, membrane stabilization, stimulation of sexual hormone secretion and elevation of sperm quality. The objective of this study was to expose the effect of taurine on spermatozoa quality and function in ornidazole-induced asthenospermia rats. We found that taurine treatment could obviously recover the decline of cauda epididymal sperm count, viability and motility, and the elevation of sperm abnormality in asthenospermia animals. Spermatozoa acrosin, LDH-X, SDH and CCO activities of model rats also were notably increased by taurine administration. The present data indicated that taurine could raise spermatozoa quality and function by elevating mitochondrial energy metabolism. Notably, taurine supplementation markedly raised serum GnRH, LH and T levels in asthenospermia rays, suggesting taurine rescued asthenosperm by means of stimulating hypothalamic-pituitary-testicular axis secretion. We also found that concentrations of asthenospermia epididymal carnitine, SA, α-Glu and ACP, and mRNA expression levels of MMP7 and IDO2 were significantly rised by taurine administration, indicating taurine may protect epididymal epithelium structure, improve secretion activity, and maintain intraluminal microenvironment homeostasis. Finally, the present results showed taurine effectively increased cauda epididymal SOD, GSH and γ-GT levels in model rats, reduced ROS and MDA production, suggesting epididymal antioxidant ability of asthenospermia rats could be elevated by taurine treatment. To sum up, our results indicated that taurine can promote spermatozoa quality and function in ornidazole-induced asthenospermia rats by facilitating epididymal epithelium secretion and luminal microenvironment homeostasis.

Efficacy and safety of morinidazole in pelvic inflammatory disease: results of a multicenter, double-blind, randomized trial.

This multicenter, double-blind, randomized, parallel-group, non-inferiority study compared the efficacy and safety of morinidazole with those of ornidazole in women with pelvic inflammatory disease. Women from 18 hospitals in China received a 14-day course of either intravenous morinidazole, 500 mg twice daily (n = 168), or intravenous ornidazole, 500 mg twice daily (n = 170). A total of 312 of 338 patients in the full analysis set (FAS) (92.3%) were included in the per protocol set (PPS) analyses, 61 (19.6%) of whom were included in the microbiologically valid (MBV) population. The clinical resolution rates in the PPS population at the test of cure (TOC, primary efficacy end point, 7-30 days post-therapy) visit were 96.86% (154/159) for morinidazole and 96.73% (148/153) for ornidazole (95% CI: -3.79% to 4.03%). The bacteriological success rates in the MBV population at the TOC visit were 100% (32/32) for morinidazole and 89.66% (26/29) for ornidazole (95% CI: -16.15% to 11.21%). Drug-related adverse events occurred less frequently with morinidazole (32.74%, 55/168) than with ornidazole (47.06%, 80/170) (p < 0.01). For women with pelvic inflammatory disease, twice-daily morinidazole for 14 days was clinically and bacteriologically as efficacious as twice-daily ornidazole for 14 days, while the former was associated with fewer drug-related adverse events than the latter.

Ornidazole-induced fixed drug reaction on sole: case report and review of the literature.

BACKGROUND: Fixed drug eruption (FDE) is a special variant of drug reaction seen on skin or mucous membrane, and typically recurs at the same location. Ornidazole-induced FDE cases have been reported extremely rare. CASE: The 48-year-old female patient was diagnosed for ornidazole-induced fixed drug reaction on the sole. The patient's history revealed that the lesion occurred for the third time in the last 6 months and she was administered ornidazole tablet 3 times by the gynecologist for genitourinary tract infection. CONCLUSION: This report presents a case of fixed drug reaction located at the sole induced by ornidazole use and a literature review.

Improved pharmacokinetic profile of levornidazole following intravenous infusion of 750mg every 24h compared with 500mg every 12h in healthy Chinese volunteers.

Levornidazole is the levo-isomer of ornidazole with similar anti-anaerobic activity and lower central neurotoxicity compared with ornidazole. This open-label, parallel, randomised, multidose trial was conducted to compare the pharmacokinetics and safety of levornidazole following intravenous (i.v.) infusion 750mg every 24h (q24h) (test group, 12 subjects) versus 500mg every 12h (q12h) (reference group, 12 subjects) for 7 days in healthy Chinese volunteers. Following i.v. infusion for 7 days, the test group showed a 33.8% lower accumulation ratio (AR) and a 45.0% higher volume of distribution of levornidazole than the reference group. The cumulative urinary excretion rate of levornidazole during the 0-72h period (Ae0-72) was 16.6±20.9% in the test group and 24.2±5.7% in the reference group. The metabolite M1/parent and M4/parent ratios were, respectively, 2.18±0.77% and 2.94±0.37% in test group and 3.15±1.09% and 3.18±0.34% in the reference group. The Ae0-72 of M1, M2 and M4 were all <10% in both groups. Both regimens were well tolerated. Drug-related adverse events were generally transient and were mild or moderate in severity. These findings support the recommendation of i.v. infusion of levornidazole 750mg q24h in clinical practice, which shows a lower AR and similar safety compared with the conventional 500mg q12h regimen. [Chinese Clinical Trial Registry identifier: ChiCTR-IPR-14005574.].

Evaluation of efficacy and tolerability of fixed dose combination of ofloxacin with ornidazole infusion (infusion O2) in the management of diarrhoea and dysentery.

Acute diarrhoea in adults is one of the most commonly encountered medical emergency in general practice and is responsible for considerable morbidity around the world. To evaluate the efficacy and tolerability of fixed dose combination of ofloxacin with ornidazole infusion (infusion O2) in the management of diarrhoea and dysentery, a study was carried out among 290 patients, age group from 18 to 65 years suffering from diarrhoea, dysentery, gastro-enteritis. Study drug infusion O2, (Medley Pharmaceutical, Mumbai) containing ofloxacin 200 mg + ornidazole 500 mg was administrated twice daily for a duration of 5 days. Number of soft or watery stool, body temperature, nausea, abdominal pain, gas and flatulence were recorded at baseline and at the end of the study. Tolerability and efficacy was evaluated based on the global assessment by the investigator based on a 3-point scale marked as excellent/good/poor. Two hundred and fifty-six-patients (160 male and 96 female) were included for final analysis, 34 patients lost to follow-up. Mean number of watery stool per day was reduced from 9.273 +/- 0.4537 to 1.375 +/- 0.07001 (p < 0.0001) by infusion O2. Body temperature was significantly reduced from 38.055 +/- 0.045 degrees C to 36.778 +/- 0.016 degrees C (p < 0.0001) at the end of the study. Pretreatment symptom nausea was significantly reduced in 90.34% of patients. Improvement in vomiting symptoms was reported in 72.35% of patients after administration of anti-emetic drug; 96.84% and 77.25% of patients reported improvement in abdominal pain and gas/flatulence respectively at the end of the trial by infusion O2. As per investigators' assessment about efficacy of trial drug, 98.43% of patients reported good to excellent and 1.56% reported poor efficacy. As per investigators' assessment about tolerability 98.43% of patients reported good to excellent and 1.17% reported poor tolerability. Minor incidences of nausea, gastritis, metallic taste were reported in 7.42%, 7.14%, and 5.85% of patients respectively. No serious adverse events were reported which led to withdrawal of patient from the study. Result of this study shows that, combination of ofloxacin with ornidazole infusion (infusion O2) significantly reduces number of watery stool and associated symptoms like nausea, abdominal pain, flatulence/gas with excellent tolerability.

Systemic ornidazole as an adjunct to non-surgical periodontal therapy in the treatment of chronic periodontitis: a randomized, double-masked, placebo-controlled clinical trial.

BACKGROUND: The purpose of this clinical trial is to evaluate the adjunctive clinical effects of the systemic administration of ornidazole (ORN) in the full-mouth scaling and root planing (SRP) of individuals with moderate-to-advanced chronic periodontitis. METHODS: Fifty-eight individuals presenting ≥12 teeth with probing depth (PD) ≥4 mm were selected. All participants were instructed on strict oral hygiene measures and were advised to use 0.2% chlorhexidine mouthwash for 1 week before being allocated to two groups. Thirty participants were randomly assigned to full-mouth SRP + placebo (control group), and 28 participants were assigned to full-mouth SRP + ORN (test group). The clinical outcomes evaluated were plaque index, gingival index, clinical attachment level (CAL), and PD. RESULTS: Fifty participants could be evaluated by ≤6 months. At 6 months, the test group had greater mean reduction (2.84 mm) in PD compared to the control group (0.84 mm) (P <0.05), and there was also a greater mean CAL reduction (2.92 mm) in the test group compared to the control group (0.92 mm) (P <0.05). CONCLUSION: The systemic use of ORN, when used in conjunction with initial periodontal treatment consisting of SRP in adults with periodontitis, achieves significantly better clinical results than initial periodontal treatment alone.