Evaluation of Ornidazole Tablets Bioequivalence in Chinese Healthy Participants Under Fasted and Fed Conditions Using Pharmacokinetic Parameters.

BACKGROUND AND OBJECTIVE: Ornidazole, the third generation of nitroimidazole derivatives after metronidazole and tinidazole, it exerts both bactericidal and antiprotozoal effects. The purpose of this study was to evaluate the pharmacokinetic and bioequivalence of two ornidazole tablets manufactured by two different manufacturers based on their pharmacokinetic parameters. PATIENTS AND METHODS: Fasted and fed healthy Chinese volunteers participated in a randomized sequence, single-dose, open-label, two-period crossover trial. There were 24 participants in both the fed study and the fasted study. Following a 7-day washout period before receiving the alternative formulation, eligible research participants were randomly assigned (1:1) to receive a single dosage of either the reference formulation or the test formulation. Following tablet administration, plasma samples were obtained over 72 h and analyzed using liquid chromatography tandem mass spectrometry (LC-MS/MS) to evaluate ornidazole contents. maximum plasma concentration (Cmax), time to Cmax (Tmax), the area under the curve (AUC) from t = 0 to infinity (AUC0-∞), AUC from t = 0 to the last quantifiable concentration (AUC0-t), half-life (t1/2), and terminal elimination rate constant (z) were evaluated as pharmacokinetic (PK) parameters. The safety evaluation involved adverse events (AEs) incidence and alterations in laboratory tests (hepatic function, blood biochemistry, hematology, and urinalysis) or vital signs (temperature, pulse, and blood pressure). RESULTS: For the bioequivalence assessment in the fast trial, the prime PK parameters comparison between the reference and test formulation revealed that the GMR (90% CI) values for AUC0-t, Cmax, and AUC0-∞ were 100.97% (99.12-102.85%), 99.88% (90.63-110.08%), and 101.12% (99.17-103.11%), respectively. For the bioequivalence assessment in the fed trial, the key PK parameters comparison between the reference and test formulations revealed that the GMR (90% CI) values for AUC0-t, Cmax, and AUC0-∞ were 103.00% (100.94-105.11%), 101.90% (99.63-104.22%), and 102.99% (100.87-105.16%), respectively. The geometric mean ratios (GMRs) for the primary pharmacokinetic parameters (Cmax, AUC0-72, and AUC0-∞) between the two formulations and the corresponding 90% confidence intervals (CIs) were all within the range of 80.00-125.00% for both the fasting and fed states. Both treatments have comparable safety profiles. CONCLUSION: The bioequivalence and tolerability of ornidazole tablet reference and test formulations were evaluated among healthy Chinese participants under both fasting and fed conditions. The results indicated that both formulations were bioequivalent and generally well tolerated; besides, the interaction between food and drug may affect drug pharmacokinetics. TRIAL REGISTRATION: CTR20212873, registered on 15 November 2021; ChiCTR2300069098, registered on 7 March 2023.

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.

Demodex-induced Lupus miliaris disseminatus faciei: A case report.

RATIONALE: Lupus miliaris disseminatus faciei (LMDF) is an inflammatory granulomatous skin disease without a clear etiology that frequently involves the middle area of the face and the upper eyelids. Pathological features of the disease include caseation necrosis and epithelioid granuloma. Consensus treatment for LMDF is currently unavailable. PATIENT CONCERNS: A 47-year-old Chinese female patient who presented with facial pruritic, erythematous papules 8 months before this study. She was diagnosed with skin tuberculosis at another hospital and given antituberculosis medication. However, the treatment was not efficacious. DIAGNOSES: In this study, the diagnosis of Demodex-induced LMDF was made by a dermatologist according to physical examination, skin biopsy pathology, and microscopic examination. INTERVENTIONS: The patient was given ornidazole tablets (500 mg twice a day) and recombinant bovine basic fibroblast growth factor gel (0.2 g/cm twice a day) for an 8-week period. OUTCOMES: Eight weeks after the treatment, the facial erythematous papules were improved, and no new skin lesions were observed. The patient showed no signs of recurrence during the 6-month follow-up. LESSONS SUBSECTIONS: This case showed that ornidazole combined with recombinant bovine basic fibroblast growth factor gel might be useful in treatment of Demodex-induced LMDF. In addition, the results suggested that pathological caseation necrosis was caused by a series of inflammatory and immune responses to Demodex infection.

Acute prostatitis after prostate biopsy under ciprofloxacin prophylaxis with or without ornidazole and pre-biopsy enema: analysis of 3. 479 prostate biopsy cases

ABSTRACT Objectives: To investigate the characteristics of cases of NIH category I acute prostatitis developed after transrectal prostate biopsy and clarifiy the risk factors and preventive factors. Materials and Methods: We retrospectively reviewed the medical records of 3.479 cases of transrectal ultrasound-guided needle biopsies performed with different prophylactic antibiotherapy regimens at two different institutions between January 2011 and February 2016. The patients of Group I have received ciprofl oxacin (n=1.523, 500mg twice daily) and the patients of Group II have received ciprofl oxacin plus ornidazole (n=1.956, 500mg twice daily) and cleansing enema combination as prophylactic antibiotherapy. The incidence, clinical features and other related microbiological and clinical data, were evaluated. Results: Mean age was 62.38±7.30 (47-75), and the mean prostate volume was 43.17±15.20 (21-100) mL. Of the 3.479 patients, 39 (1.1%) developed acute prostatitis after the prostate biopsy procedure. Of the 39 cases of acute prostatitis, 28/3.042 occurred after the first biopsy and 11/437 occurred after repeat biopsy (p=0.038). In Group I, 22 of 1.523 (1.4%) patients developed acute prostatitis. In Group II, 17 of 1.959 (0.8%) patients developed acute prostatitis. There was no statistical difference between the two groups according to acute prostatitis rates (X2=2.56, P=0.11). Further, hypertension or DM were not related to the development of acute prostatitis (P=0.76, X2=0.096 and P=0.83, X2=0.046, respectively). Conclusions: Repeat biopsy seems to increase the risk of acute prostatitis, while the use of antibiotics effective for anaerobic pathogens seems not to be essential yet.

Acute prostatitis after prostate biopsy under ciprofloxacin prophylaxis with or without ornidazole and pre-biopsy enema: analysis of 3.479 prostate biopsy cases.

OBJECTIVES: To investigate the characteristics of cases of NIH category I acute prostatitis developed after transrectal prostate biopsy and clarifiy the risk factors and preventive factors. MATERIALS AND METHODS: We retrospectively reviewed the medical records of 3.479 cases of transrectal ultrasound-guided needle biopsies performed with different prophylactic antibiotherapy regimens at two different institutions between January 2011 and February 2016. The patients of Group I have received ciprofloxacin (n=1.523, 500mg twice daily) and the patients of Group II have received ciprofloxacin plus ornidazole (n=1.956, 500mg twice daily) and cleansing enema combination as prophylactic antibiotherapy. The incidence, clinical features and other related microbiological and clinical data, were evaluated. RESULTS: Mean age was 62.38 ± 7.30 (47-75), and the mean prostate volume was 43.17 ± 15.20 (21-100) mL. Of the 3.479 patients, 39 (1.1%) developed acute prostatitis after the prostate biopsy procedure. Of the 39 cases of acute prostatitis, 28/3.042 occurred after the fi rst biopsy and 11/437 occurred after repeat biopsy (p=0.038). In Group I, 22 of 1.523 (1.4%) patients developed acute prostatitis. In Group II, 17 of 1.959 (0.8%) patients developed acute prostatitis. There was no statistical difference between the two groups according to acute prostatitis rates (X2=2.56, P=0.11). Further, hypertension or DM were not related to the development of acute prostatitis (P=0.76, X2=0.096 and P=0.83, X2=0.046, respectively). CONCLUSIONS: Repeat biopsy seems to increase the risk of acute prostatitis, while the use of antibiotics effective for anaerobic pathogens seems not to be essential yet.

Development and characterization of rapid dissolving ornidazole loaded PVP electrospun fibers.

Gingivitis is a common and mild form of periodontal disease and can be described as a limited inflammation of the gingiva. This study aims to develop and characterize rapid releasing mucoadhesive fibers containing ornidazole with electrospinning process for the treatment of gingivitis. Polyvinylpyrrolidone (PVP) was chosen as a polymer and used at different concentrations of 10%, 12.5%, and 15%. Scanning electron microscopy images showed that fiber diameters increased with increasing polymer concentrations. Tensile strength and elongation at break values of fibers increased with increasing PVP amount, whereas the loading of ornidazole into the fibers decreased these parameters. The contact angle values of all fibers were found to be 0° due to the hydrophilic nature of PVP. Ornidazole was released within 5 min and diffused from all of the fibers faster than that of gel and solution formulations. Electrospun ornidazole fibers were found efficient against Porphyromonas gingivalis in antimicrobial activity studies. The results demonstrated that ornidazole loaded fibers could be a potential drug delivery system for the treatment of gingivitis.

Alterations in intestinal microbiota of colorectal cancer patients receiving radical surgery combined with adjuvant CapeOx therapy.

An intricate relationship exists and interactions occur between gut microbiota and colorectal cancer (CRC). Radical surgery combined with adjuvant chemotherapy (AC) serves as the mainstream therapeutic scheme for most CRC patients. The current research was conducted to assess the effect of surgery or chemotherapy on gut microbiota. Forty-three CRC patients who received radical surgery and AC were enrolled. Fecal samples were collected preoperatively, postoperatively, and after the first to fifth cycles of postoperative chemotherapy. The microbial community of each sample was analyzed using high throughput 16S rRNA amplicon sequencing. Compared with preoperative samples, fecal samples collected postoperatively exhibited a significant decrease of obligate anaerobes, tumor-related bacteria, and butyric acid-producing bacteria. However, a significant increase of some conditional pathogens was observed. In addition, the AC regimen (CapeOx) was found to alter intestinal microbiota dramatically. In particular, several changes were observed after chemotherapy including an increase of pathogenic bacteria, the "rebound effect" of chemotherapy-adapted bacteria, the shift of lactate-utilizing microbiota from Veillonella to Butyricimonas and Butyricicoccus, as well as the decrease of probiotics. Both radical surgery and CapeOx chemotherapy exert a non-negligible effect on the gut microbiota of CRC patients. Microbiota-based intervention may be beneficial for patients during postoperative clinical management.

Mucoadhesive buccal film containing ornidazole and dexamethasone for oral ulcers: in vitro and in vivo studies.

A bilayered mucoadhesive buccal film containing a combination of ornidazole (OD) and dexamethasone sodium phosphate (DEX) was prepared using solvent casting to treat oral ulcers. Films were systematically evaluated in vitro to obtain the optimum formulation. The therapeutic effects of these films were investigated in the rabbit oral ulcer model and the in vivo release of OD and DEX in the human oral cavity was also evaluated. The backing layer contained ethyl cellulose and an optimal mucoadhesive layer containing both OD and DEX was produced. Films from the optimum formulation were 0.427 ± 0.015 mm thick, weighed 55.89 ± 0.79 mg, and had a surface pH of 6.34 ± 0.01. The drug content of the optimum formulation approximated the theoretical value with good uniformity (2.959 ± 0.106 mg/cm2 for OD and 0.877 ± 0.031 mg/cm2 for DEX). The formulation showed favorable swelling characteristics and both drugs were released at >95% after 4 h. Moreover, the compound film had a statistically significant effect on mucosal repair and reduced ulcer inflammation without stimulating the human oral mucosa. Cmax of OD in saliva was 37.04 µg/ml and that of DEX was 9.737 µg/ml. Given promising therapeutic effects, the compound film developed here could become a local drug delivery device for treating oral ulcers.

Comparison of intravenous versus combined oral and intravenous antimicrobial prophylaxis (COMBINE) for the prevention of surgical site infection in elective colorectal surgery: study protocol for a multicentre, double-blind, randomised controlled clinical trial.

INTRODUCTION: Surgical site infections (SSIs) account for 30% of all healthcare-associated infections, with reported rates ranging from 8% and 30% after colorectal surgery and are associated with increased morbidity and mortality rates, length of hospital stay and costs in healthcare. Administration of systemic antimicrobial prophylaxis before surgery is recommended to reduce the risk of SSI, but the optimal regimen remains unclear. We aim to evaluate whether a combined oral and intravenous antimicrobial prophylaxis could be more effective to reduce the incidence of SSI after colorectal surgery, as compared with the standard practice of intravenous antimicrobial prophylaxis alone. METHODS AND ANALYSIS: Comparison of intravenous versus combined oral and intravenous antimicrobial prophylaxis (COMBINE) trial is a randomised, placebo-controlled, parallel, double-blind, multicentre study of 960 patients undergoing elective colorectal surgery. Patients will be randomly allocated in a 1:1 ratio to receive either combined oral and intravenous antimicrobial prophylaxis or intravenous antibiotic prophylaxis alone, stratified by centre, the surgical procedure (laparoscopic or open surgery) and according to the surgical skin antisepsis (chlorexidine-alcohol or povidione-iodine alcoholic solution). The primary endpoint is the rate of SSI by day 30 following surgery, with SSI defined by the criteria developed by the Centers for Disease Control and Prevention. Data will be analysed on the intention-to-treat principle and a per-protocol basis. ETHICS AND DISSEMINATION: COMBINE trial has been approved by an independent ethics committee for all study centres. Participant recruitment began in May 2016. Results will be published in international peer-reviewed medical journals. TRIAL REGISTRATION NUMBER: EudraCT 2015-002559-84; NCT02618720.

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.

Preparation, in Vitro and in Vivo Evaluations of Compound Calculus Bovis Sativus and Ornidazole Film.

The aim of this study was to develop and to investigate a film of compound Calculus Bovis Sativus (CBS) and ornidazole film. A uniform mucoadhesive film was herein successfully obtained by a film-forming solusion containing insoluable drug. This film, as a valid adjunct for the treatment of oral mucosal ulcer, consisted of two main drugs (CBS, ornidazole) and three polymers (hydroxypropyl methyl cellulose, chitosan, poly(vinyl alcohol) (PVA)). The film was prepared with the film-forming suspension, using casting-solvent evaporation technique. The drug content, release behavior, swelling index and mucoadhesive properties of the film were detected. Then the effects of the prepared film on a glacial acetic acid-induced oral mucosal ulceration model of rabbits were evaluated. Moreover, the in vivo release of bilirubin and ornidazole in saliva were also detected in the oral mucosae of healthy volunteers. The films showed favorable in vitro drug release behaviors and swelling properties. Mucosal wounds in the animals were significantly relieved. With the films well tolerated, the salivary concentrations of ornidazole were maintained above the minimum inhibitory concentration against CBS for about 2 h. The compound CBS and ornidazole film functioned better than the film only containing CBS and ornidazole did. Therefore, it is a potentially efficient drug delivery system for the treatment of oral ulcers.

Treatment of mites folliculitis with an ornidazole-based sequential therapy: A randomized trial.

OBJECTIVE: Treatment of Demodex infestations is often inadequate and associated with low effective rate. We sought to evaluate the efficacy of an ornidazole-based sequential therapy for mites folliculitis treatment. METHODS: Two-hundred patients with mites folliculitis were sequentially treated with either an ornidazole- or metronidazole-based regimen. Sebum cutaneum was extruded from the sebaceous glands of each patient's nose and the presence of Demodex mites were examined by light microscopy. The clinical manifestations of relapse of mites folliculitis were recorded and the subjects were followed up at 2, 4, 8, and 12 weeks post-treatment. RESULTS: Patients treated with the ornidazole-based regimen showed an overall effective rate of 94.0%. Additionally, at the 2, 4, 8, and 12-week follow-up, these patients had significantly lower rates of Demodex mite relapse and new lesion occurrence compared with patients treated with the metronidazole-based regimen (P < 0.05). CONCLUSION: Sequential therapy using ornidazole, betamethasone, and recombinant bovine basic fibroblast growth factor (rbFGF) gel is highly effective for treating mites folliculitis.

In vitro simulation of in vivo pharmacokinetic model with intravenous administration via flow rate modulation.

The aim of this paper was to propose a method of flow rate modulation for simulation of in vivo pharmacokinetic (PK) model with intravenous injection based on a basic in vitro PK model. According to the rule of same relative change rate of concentration per unit time in vivo and in vitro, the equations for flow rate modulation were derived using equation method. Four examples from literature were given to show the application of flow rate modulation in the simulation of PK model of antimicrobial agents in vitro. Then an experiment was performed to confirm the feasibility of flow rate modulation method using levo-ornidazole as an example. The accuracy and precision of PK simulations were evaluated using average relative deviation (ARD), mean error and root mean squared error. In vitro model with constant flow rate could mimic one-compartment model, while the in vitro model with decreasing flow rate could simulate the linear mammillary model with multiple compartments. Zero-order model could be simulated using the in vitro model with elevating flow rate. In vitro PK model with gradually decreasing flow rate reproduced the two-compartment kinetics of levo-ornidazole quite well. The ARD was 0.925 % between in vitro PK parameters and in vivo values. Results suggest that various types of PK model could be simulated using flow rate modulation method without modifying the structure. The method provides uniform settings for the simulation of linear mammillary model and zero-order model based on in vitro one-compartment model, and brings convenience to the pharmacodynamic study.

Clinical and diagnostic features and treatment of giardiasis.

Giardia is the most common causes of protozoan diarrhea that lead to significant morbidity and mortality worldwide. Giardiasis can be cause of disturbance of host immune response. The treatment of Giardiasis is unsuccessful in some cases. The purpose of this study was to determine the clinical features and the content of secretory immunoglobulin A (sIgA) among adults and to evaluate efficiency of new plant preparation "Sausalin". The clinical studies were conducted in Karaganda Regional Infection Hospital (Kazakhstan). 250 patients with giardiasis were randomly assigned to receive sausalin at a dose 720 mg/day or ornidazole at 1500 mg/day. Clinical symptoms of giardisis and efficiency of treatment were evaluated. Protozoal clearance rate and clinical symptoms were assessed. Stool samples were collected from 40 patients and examined the content of sIgA. Our study found the prevalence of abdominal pain, dyspeptic syndrome and the symptoms of intoxication in patients with giardiasis. The increase the level of sIgA was detected, especially in females (88 mg/l). Sausalin was more effectiveness than ornidazole. After the treatment, the clearance rate of giardia (85.71% vs. 42.19%; P<0.05) and the clinical efficacy were significantly higher in the sausalin-treated group than in the ornidazole-treated group. The features of clinic manifestations of giardiasis were identified in population of Kazakhstan. Our data suggest the higher level of sIgA was significantly associated with features of clinic manifestations that the participant had. Treatment with sausalin was more effective than treatment with ornidazole. Further research is needed to explain the existence relationship between Giardia infection and host immune response.

Enantioselective determination of ornidazole in human plasma by liquid chromatography-tandem mass spectrometry on a Chiral-AGP column.

A rapid, sensitive, and enantioselective method was developed and validated for determination of ornidazole enantiomers in human plasma by liquid chromatography-tandem mass spectrometry. Ornidazole enantiomers were extracted from 100µl of plasma using ethyl acetate. Baseline chiral separation (Rs=2.0) was obtained within 7.5min on a Chiral-AGP column (150mm×4.0mm, 5µm) using an isocratic mobile phase of 10mM ammonium acetate/acetic acid (100/0.01, v/v). Stable isotopically labeled R-(+)-d5-ornidazole and S-(-)-d5-ornidazole were synthesized as internal standards. Acquisition of mass spectrometric data was performed in multiple reaction monitoring mode via positive electrospray ionization, using the transitions of m/z 220→128 for ornidazole enantiomers, and m/z 225→128 for d5-ornidazole enantiomers. The method was linear in the concentration range of 0.030-10.0µg/ml for each enantiomer. The lower limit of quantification for each enantiomer was 0.030µg/ml. The relative standard deviation values of intra- and inter-day precision were 1.8-6.2% and 1.5-10.2% for R-(+)-ornidazole and S-(-)-ornidazole, respectively. The relative error values of accuracy ranged from -4.5% to 1.2% for R-(+)-ornidazole and from -5.4% to -0.8% for S-(-)-ornidazole. The validated method was successfully applied to a stereoselective pharmacokinetic study of ornidazole after oral administration of 1000mg racemic ornidazole.

Formulation and development of oral dry suspension using taste masked Ornidazole particles prepared using Kollicoat(®) Smartseal 30 D.

The purpose of this work was to taste mask highly bitter active, Ornidazole by means of particle coating. The aim of the work was further extended into formulating these coated particles into an acceptable oral dosage form such as dry suspension. Ornidazole drug particles were coated using Kollicoat(®) Smartseal 30 D as a taste masking polymer. Kollicoat(®) Smartseal 30 D is a methyl methacrylate - diethylaminoethyl methacrylate copolymer (6:4). Successful taste masking was achieved for Ornidazole with both top spray and bottom spray techniques using fluid bed processor. Effective taste masking was achieved at a weight gain of 50% w/w and 40% w/w for bottom and top spray techniques respectively without having a significant effect on the release pattern. A taste masked dry suspension was prepared with around 80% w/w coated Ornidazole particles and pH was maintained around 7-8. The suspension prepared with these coated Ornidazole particles, which were maintained in the alkaline pH was found to be stable for 7 days without affecting the taste. The bitter taste intensity was evaluated using volunteers by comparison of test samples with standard solutions containing Ornidazole at various concentrations. Thus, Kollicoat(®) Smartseal 30 D was found to be an effective polymer for taste masking of a bitter active like Ornidazole. The formulation development of taste masked dry suspensions was only possible due to unique properties possessed by Kollicoat(®) Smartseal 30 D.

Investigation of chiral inversion and pharmacokinetics of laevo-ornidazole by high-performance liquid chromatography.

WHAT IS KNOWN AND OBJECTIVE: Laevo-ornidazole is an enantiomer of ornidazole, a 5-nitroimidazole antimicrobial agent. It is not known whether chiral inversion of laevo-ornidazole occurs in humans. The objective of this study was to investigate the possible chiral inversion and pharmacokinetics of the drug in vivo. METHODS: We developed a stereo-specific high-performance liquid chromatographic method for investigating chiral inversion of the drug and a standard high-performance liquid chromatography (HPLC) for the routine assay of the drug in pharmacokinetic studies. We report on the pharmacokinetics of the drug following single dose and multiple doses and investigate the effect of food in healthy volunteers. RESULTS AND DISCUSSION: There was no chiral inversion of laevo-ornidazole in vivo. In the pharmacokinetic study of the drug in healthy Chinese volunteers, food intake affected the absorption rate of laevo-ornidazole but not the extent. WHAT IS NEW AND CONCLUSION: We present the first reported method for the chiral separation of ornidazole in human plasma. We demonstrate the absence of chiral inversion of laevo-ornidazole in vivo. Given the absence on in vivo chiral inversion, we also report and validate a simplified non-chiral method for the determination of laevo-ornidazole. We show that although food can affect the absorption rate of laevo-ornidazole, the extent was unaffected.

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.

Microbiological outcomes of systemic ornidazole use in chronic periodontitis. Part II.

OBJECTIVE: Antimicrobials are increasingly being used as adjuncts to non-surgical or surgical periodontal therapy. The main purpose of the present analysis was to evaluate the effect of systemic ornidazole (ORN) on total anaerobic microbial counts of subjects with moderate to advanced chronic periodontitis (CP). METHODS: This was a single-center, double-blinded, placebo-controlled, randomized clinical trial of six months duration. Fifty-eight subjects presenting with at least 12 teeth with probing depth (PD) > or = 4 mm were selected. Thirty subjects received full-mouth scaling and root planing (SRP) + placebo (control group) and 28 subjects received full-mouth SRP + ORN (test group). The total anaerobic counts were analyzed by collecting subgingival plaque from deepest pockets at baseline (B/L), 1 week, 1 month, 3 months and 6 months. RESULTS: Paired and unpaired t-tests were used to determine the inter- and intra-group differences. Fifty subjects were evaluated up to six months. There was a significant difference in the number of anaerobes in the two groups at all the intervals except B/L (p<0.05). CONCLUSION: The systemic use of ORN very efficiently reduced the microbial load in the group that received antibiotics.