Role of doxycycline in the treatment of dengue infection: An open-label, randomized, controlled, pilot trial

Objective:To measure the effect of doxycycline on inflammatory marker[IL-6,TNF-α,ferritin and C reactive protein(CRP)]levels in patients with dengue infection.Methods:A single-centre,open-label,parallel-group randomized controlled trial was done in PGIMER Chandigarh from June 2021 to October 2022.Patients were randomized using a simple randomization process into two groups:the doxycycline treatment group(n=35)and the control group(n=34).Patients in the treatment group were given oral doxycycline 100 mg twice daily for five days along with standard treatment,whereas patients in the control group received only standard treatment.The objective was to measure the effect of doxycycline on inflammatory markers in dengue infection.Results:On comparative analysis at day 5,there was a statistically significant reduction in the median values of ferritin and CRP in cases compared to the control group(ferritin:P=0.006 and CRP:P=0.006).No significant reduction was noted in the levels of IL-6 and TNF-α.Conclusions:Doxycycline treatment led to a reduction of inflammatory markers in dengue infection.

Bullous Pemphigoid Induced by Doxycycline: Case Report and Literature Review

Bullous pemphigoid (BP) is the most prevalent autoimmune sub-epidermal blistering disease that affects mainly the elderly and could lead to serious morbidity. It has numerous risk factors and triggers, including an aging population with several comorbidities and drug exposure. In the published paper, we reported a case about a 32 years old male patient with unknown medical conditions who presented with erythematous patches and plaques on the scalp, face, and trunk with scattered blisters two weeks after initiating doxycycline treatment for folliculitis. The exact pathogenesis of the drug-reaction in drug- associated bullous pemphigoid (DABP) remains controversial. In conclusion, it is crucial for clinicians to be aware of DABP when prescribing doxycycline. The purpose of this case report is to raise awareness of the possible association between bullous pemphigoid and doxycycline.

The dose regimen formulation of doxycycline hydrochloride and florfenicol injection based on ex vivo pharmacokinetic-pharmacodynamic modeling against the Actinobacillus pleuropneumoniae in pigs

Doxycycline hydrochloride and florfenicol combination(DoxHcl&FF)is an effective treatment for respiratory diseases.In the study,our objective Was to evaluate the activity of DoxHcl&FF against Actinobacillus pleuropneumoniae(APP)in porcine pulmonary epithelial lining fluid(PELF)and the optimal dosage scheme to avoid the development of resistance.The DoxHcl&FF Was administered intramuscularly(IM)at 20mg/kg,and the PELF was collected at differ-ent time points.The minimum inhibitory concentration(MIC)and time-mortality curves were also included in the study.Based on the sigmoid Emax equation and dose equations,the study integrated the in vivo pharmacokinetic data of infected pigs and ex vivo pharmacodynamic data to obtain the area under concentration time curve(AUCo-24h)MIC values in PELF and achieve bacteriostatic activity,bactericidal activity and the virtual eradication of bacteria.The study showed that the combination of DoxHcl and FF caused no significant changes in PK parameters.The peak concentration(Cmax)of FF in healthy and diseased pigs was 8.87±0.08 and 8.67±0.07μg/mL,the_AUCo-24h were.172.75±2.52 and 18022±3.13 h-μg/mL,the Cmax of DoxHcl was 7.91±0.09 and 7.99±0.05μg/mL,and the AUCo-24h was 129.96±3.70 h-μg/mL and 169.82±4.38 h-μg/mL.DoxHcl&FF showed strong concentra-tion-dependent tendencies.The bacteriostatic,bactericidal,and elimination activity were calculated as 5.61,18.83 and 32.68 h,and the doses were 1.37(bacteriostatic),4.59(bactericidal)and 7.99(elimination)mg/kg.These findings indicated that the calculated recommended dose could assist in achieving more precise administration,increasing the effectiveness of DoxHcl&FF treatment for APP infections.

Fixed-Dose Combination (FDC) Formulation of Quinine Sulphate-Doxycycline (Qidox) for Malaria Therapy

Background: One of the deadliest parasite infections is malaria. A combination of quinine sulphate and doxycycline is another therapeutic option for malaria that is resistant to chloroquine and is anticipated to be able to both combat the issue of anti-malarial medication resistance as well as the compliance to malaria therapy that is still raging in certain locations of Indonesia. Aim: This study will focus on evaluating the possibility of interaction between quinine sulphate and doxycycline followed by formulating the fixed-dose combination of both active pharmaceutical ingredients. Method: The study was designed as a laboratory experiment and applied some examinations. The examination from the organoleptic test of active pharmaceutical ingredients powder, crystallography analysis, and physical analysis of fixed-dose tablet including hardness, friability, and disintegration time testing. Result: The crystallography study reported there was no physical interaction found between quinine sulphate and doxycycline. The formula found excellent tablet printability with a composition of Quinine sulphate and doxycycline (Qidox). Conclusion: quinine sulphate with doxycycline can be combined into one tablet as Fixed-Dose Combination (FDC).

A Comparative Evaluation of Polystyrene Divinylbenzene Copolymer HPLC Columns on the Chromatographic Performance of the Compendial Method for Doxycycline Hyclate Capsules: Implications for Method Implementation of a Medical Countermeasure Medication

The purpose of this study was to evaluate the impact of polystyrene divinylbenzene copolymer HPLC columns on the chromatographic performance of the USP compendial method for doxycycline hyclate. The compendial method was implemented based on the assessment of the chromatographic performance of six USP defined L21 polystyrene divinylbenzene HPLC columns. Modifications to the method were based on USP for chromatography. The method was validated for the determination of doxycycline hyclate and its impurities in commercially available drug products. A number of different polystyrene-divinylbenzene columns were tested and failed to provide selectivity for the resolution of doxycycline and its impurities. Separation was optimally achieved on an Agilent PLPR-S column (250 × 4.6 mm, 8 μm) by using an Agilent 1260 series HPLC system. Doxycycline hyclate and its impurities were eluted isocratically at a flow rate of 1 mL/min with mobile phase and detected at 270 nm. The column temperature was maintained at 60oC. The method was validated according to USP category I requirements for Assay. Validation acceptance criteria were met in all cases. The analytical range for doxycycline hyclate was 50 - 250 μg/mL and the linearity was r2 > 0.999 over three days. The method was determined to be specific. Both accuracy (95.1% - 102.4%) and precision (0.50% - 4.8%) were established across the analytical range for low, intermediate and high QC concentrations. Method applicability was demonstrated by analyzing marketed products of doxycycline hyclate, in which results showed potency meeting USP acceptance criteria. In conclusion, this study described the remarkable differences in selectivity that were encountered during the implementation phase for the compendial methods for doxycycline and its impurities in marketed products and it could be used in the future to assss the product quality of doxycycline hyclate capsules stored in the National stockpiles.

Doxycycline抑制大肠癌LS174T细胞侵袭的体外实验研究

目的:观察多西环素(Doxycycline)在体外对LS174T侵袭能力的抑制作用,并尝试探讨该抑制作用的分子机制。方法:1)MTT法观察Doxycycline对LS174T细胞粘附力的影响;Transwell小室法检测不同浓度Doxycycline对细胞侵袭和运动能力的抑制作用;2)RT-PCR法检测不同浓度Doxycycline作用48h后,MMP2的mRNA表达情况,同时明胶酶谱法检测MMP2分泌。结果:1)Doxycycline能够以剂量依赖方式抑制大肠癌LS174T细胞的体外运动和侵袭能力,但不影响其粘附能力;2)Doxycycline能够抑制LS174T细胞MMP2的mRNA表达。结论:Doxycycline在体外能够有效地抑制大肠癌LS174T细胞的侵袭、转移,其中MMP2是抑制大肠癌细胞LS174T的一个有效靶点。

Doxycycline抑制人肝癌细胞系HepG_2生长的实验研究

目的:观察多西环素(Doxycycline)对人肝细胞性肝癌细胞系HepG2生长抑制和凋亡的作用,并初步探讨其作用机制。方法:不同浓度的Doxycycline(5、10、20、30和50mg/L)对体外培养人肝癌细胞系HepG2进行不同的时间干预(24、48和72h),MTT法测定细胞生长抑制率,TUNEL法检测细胞凋亡率,免疫细胞化学检测Fas、FasL及MMP-2蛋白表达的变化。结果:Doxycycline作用HepG2细胞48h和72h后,细胞生长被明显抑制,与无药对照组比较差异有统计学意义(P<0.001),且呈时间、浓度依赖趋势。其细胞凋亡率较无药对照组也明显升高(P<0.01);20mg/L Doxycycline作用于癌细胞48h后,实验组FasL蛋白阳性表达较无药对照组明显升高,MMP-2蛋白阳性表达较无药对照组明显降低,两组差异均有统计学意义(P<0.01),而Fas蛋白表达则差异无统计学意义(P>0.05)。结论:Doxycycline对人肝癌细胞系HepG2具有明显的生长抑制和促凋亡作用,其机制可能与下调MMP-2、上调FasL从而启动Fas/FasL膜受体途径有关。

Low efficacy of levofloxacin-doxycycline-based third-line triple therapy for Helicobacter pylori eradication in Italy

AIM:To evaluate a levofloxacin-doxycycline-based triple therapy with or without a susceptibility culture test in non-responders to Helicobacter pylori(H.pylori) eradication.METHODS:A total of 142(99 women,43 men; mean 53.0 ± 12.7 years) non-responders to more than two H.pylori eradication therapies underwent susceptibility culture tests or were treated with a seven-day triple therapy consisting of esomeprazole,20 mg b.i.d.,levofloxacin,500 mg b.i.d.,and doxycycline,100 mg b.i.d.,randomly associated with(n = 71) or without(n = 71) Lactobacillus casei DG.H.pylori status was checked in all patients at enrollment and at least 8 wk after the end of therapy.Compliance and tolerability of regimens were also assessed.RESULTS:H.pylori eradication was achieved in < 50% of patients [per prototol(PP) = 49%; intention to treat(ITT) = 46%].Eradication rate was higher in patients administered probiotics than in those without(PP = 55% vs 43%; ITT = 54% vs 40%).Estimated primary resistance to levofloxacin was 18% and multiple resistance was 31%.Therapy was well tolerated,and side effects were generally mild,with only one patient experiencing severe effects.CONCLUSION:Third-line levofloxacin-doxycycline triple therapy had a low H.pylori eradication efficacy,though the success and tolerability of this treatment may be enhanced with probiotics.

Treatment of ocular rosacea: comparative study of topical cyclosporine and oral doxycycline

AIM: To compare the effectiveness of topical cyclosporine A emulsion with that of oral doxycycline for rosacea associated ocular changes and dry eye complaints.METHODS: One hundred and ten patients with rosacea were screened. Thirty-eight patients having rosacea associated eyelid and ocular surface changes and dry eye complaints were included in the study. Patients were randomly divided into two groups: nineteen patients were given topical cyclosporine twice daily and nineteen patients were given oral doxycycline 100 mg twice daily for the first month and once daily for the following two months. Symptom and sign scores, ocular surface disease index questionnarie and tear function tests were evaluated at baseline and monthly for 3mo. Three months after results were compared with that of baseline.RESULTS: Mean values of symptom, eyelid sign and corneal/conjunctival sign scores of each treatment group at baseline and 3mo after treatments were compared and both drugs were found to be effective on rosacea associated ocular changes(P 【0.001). Cyclosporine was more effective in symptomatic relief and in the treatment of eyelid signs(P =0.01). There was statistically significant increase in the mean Schirmer score with anesthesia and tear break up time scores in the cyclosporine treatment group compared to the doxycycline treatment group(P 【0.05).CONCLUSION: Cyclosporine as a topical drug can be used in the treatment of rosacea associated ocular complications because it is more effective than doxycycline. In addition ocular rosacea as a chronic disease requires long term treatment and doxycycline has various side effects limiting its long term usage.

Establishment of an artificial β-cell line expressing insulin under the control of doxycycline

AIM: Artificial beta-cell lines may offer an abundant source of cells for the treatment of type I diabetes, but insulin secretion in beta-cells is tightly regulated in physiological conditions. The Tet-On system is a &quot;gene switch&quot; system, which can induce gene expression by administration of tetracycline (Tet) derivatives such as doxcycline (Dox). Using this system, we established 293 cells to an artificial cell line secreting insulin in response to stimulation by Dox. METHODS: The mutated proinsulin cDNA was obtained from plasmid pcDNA3.1/C-mINS by the polymerase chain reaction (PCR), and was inserted downstream from the promoter on the expression vector pTRE2, to construct a recombined expression vector pTRE2mINS. The promoter on pTRE2 consists of the tetracycline-response element and the CMV minimal promoter and is thus activated by the reverse tetracycline-controlled transactivator (rtTA) when Dox is administrated. pTRE2mINS and plasmid pTK-Hyg encoding hygromycin were co-transfected in the tet293 cells, which express rtTA stably. Following hygromycin screening, the survived cells expressing insulin were selected and enriched. Dox was used to control the expression of insulin in these cells. At the levels of mRNA and protein, the regulating effect of Dox in culture medium on the expression of proinsulin gene was estimated respectively with Northern blot, RT-PCR, and radioimmunoassay. RESULTS: From the 28 hygromycin-resistant cell strains, we selected one cell strain (tet293/Ins6) secreting insulin not only automatically, but in response to stimulation by Dox. The amount on insulin secretion was dependent on the Dox dose (0,10,100,200,400,800 and 1000 microg.L(-1)), the level of insulin secreted by the cells treated with Dox (1000 microg.L(-1)) was 241.0pU.d(-1).cell(-1) , which was 25-fold that of 9.7pU.d(-1).cell(-1) without Dox treatment. Northern blot analyses and RT-PCR further confirmed that the transcription of insulin gene had already been up-regulated after exposing tet293/Ins6 cells to Dox for 15 minutes, and was also induced in a dose-dependent manner. However, the concentration of insulin in the media did not increase significantly until 5 hours following the addition of Dox. CONCLUSION: Human proinsulin gene was transfected successfully and expressed efficiently in 293 cells, and the expression was modulated by tetracycline and its derivatives, improving the accuracy, safety, and reliability of gene therapy, suggesting that conditional establishment of artificial beta-cells may be a useful approach to develop cellular therapy for diabetes mellitus.

Doxycycline blocks gastric ulcer by regulating matrix metalloproteinase-2 activity and oxidative stress

AIM: To examine the effect of doxycycline on the activity of matrix metalloproteinases (MMPs) and oxidative stress in gastric tissues of rats following gastric injury.METHODS: Gastric ulcers were generated in rats by administration of 70% ethanol,and activity of doxycycline was tested by administration 30 min prior to ethanol.Similarly,the effect of doxycycline was tested in an indomethacin-induced gastric ulcer model.The activities and expression of MMPs were examined by zymography and Western blot analysis.RESULTS: Gastric injury in rats as judged by elevated ulcer indices following exposure to ulcerogen,either indomethacin or ethanol,was reversed significantly by doxycycline.Indomethacin-induced ulcerated gastric tissues exhibited about 12-fold higher proMMP-9 activity and about 5-fold higher proMMP-3 activity as compared to control tissues.Similarly,ethanol induced about 22-fold and about 6-fold higher proMMP-9 and proMMP-3 activities,respectively,in rat gastric tissues.Both proMMP-9 and MMP-3 activities were markedly decreased by doxycycline in ulcerogen treated rat gastric tissues.In contrast,the reduced MMP-2 activity in ulcerated tissues was increased by doxycycline during ulcer prevention.On the other hand,doxycycline inhibited significantly proMMP-9,-2 and -3 activities in vitro.In addition,doxycycline reduced oxidative load in gastric tissues and scavenged H2O2 in vitro.Our results suggest a novel regulatory role of doxycycline on MMP-2 activity in addition to inhibitory action on MMP-9 and MMP-3 during prevention of gastric ulcers.CONCLUSION: This is the first demonstration of dual action of doxycycline,that is,regulation of MMP activity and reduction of oxidative stress in arresting gastric injury.

Esophageal ulceration complicating doxycycline therapy

AIM;TO report present state of iatrogenic drug-induced esophageal injury(DIEI)induced by medications in a private clinic. METHODS:Iatrogenic drug-induced esophageal injury (DIEI)induced by medications has been more frequently reported.In a private clinic we encountered 36 cases of esophageal ulcerations complicating doxycycline therapy in a mainly younger Saudi population(median age 29 years). RESULTS:The most frequent presenting symptoms were odynophagia,retrosternal burning pain and dysphagia(94 %, 75 % and 56 %,respectively).The diagnosis was according to medical history and confirmed by endoscopy in all patients. Beside withdrawal of doxycycline,when feasible,all patients were treated with a proton-pump inhibitor(PPI)and a prokinetic.Thirty patients who reported to the clinic after treatment were improved within 1-7(median 1.7)days. CONCLUSION:Esophageal ulceration has to be suspected in younger patients with odynophagia,retrosternal burning pain and/or dysphagia during the treatment with doxycycline.

Doxycycline induces bone repair and changes in Wnt signalling

Doxycycline （DOX） exhibits anti-inflammatory and MMP inhibitory properties. The objectives of this study were to evaluate the effects of DOX on alveolar bone repair. Controls （CTL） and DOX-treated （10 and 25 mg. kg- 1） molars were extracted, and rats were killed 7 or 14 days later. The maxillae were processed and subjected to histological and immunohistochemical assays. Hematoxylin-eosin staining （7th day） revealed inflammation in the CTL group that was partly reversed after DOX treatment. On the 14th day, the CTL group exhibited bone neoformation, conjunctive tissue, re-epithelization and the absence of inflammatory infiltrate. DOX-treated groups exhibited complete re-epithelization, tissue remodelling and almost no inflammation. Picrosirius red staining in the DOXlO group （7th and 14th days） revealed an increased percentage of type I and III collagen fibres compared with the CTL and DOX25 groups. The DOXlO and DOX25 groups exhibited increases in osteoblasts on the 7th and 14th days. However, there were fewer osteoclasts in the DOXlO and DOX25 groups on the 7th and 14th days. Wnt-lOb- immunopositive cells increased by 130% and 150% on the 7th and 14th days, respectively, in DOX-treated groups compared with the CTL group. On the 7th day, Dickkopf （Dkk）-I immunostaining was decreased by 63% and 46% in the DOXlO and DOX25 groups, respectively. On the 14th day, 69% and 42% decreases in immunopositive cells were observed in the DOXlO and DOX25 groups, respectively, compared with the CTL group. By increasing osteoblasts, decreasing osteoclasts, activating Wnt lOb and neutralising Dkk, DOX is a potential candidate for bone repair in periodontal diseases.

Role of clove oil in solvent exchange-induced doxycycline hyclate-loaded Eudragit RS in situ forming gel

Solvent exchange induced in situ forming gel(ISG) is the promising drug delivery system for periodontitis treatment owing to the prospect of maintaining an effective high drug level in the gingival crevicular fluid. In the present study, the influence of clove oil(CO) on the characteristics of doxycycline hyclate(DH)-loaded ISG comprising Eudragit RS(ERS) was investigated including viscosity/rheology, syringeability, in vitro gel formation/drug release, matrix formation/solvent diffusion and antimicrobial activities. CO could dissolve ERS and increase the viscosity of ISG and its hydrophobicity could also retard the diffusion of solvent and hinder the drug diffusion; thus, the minimization of burst effect and sustained drug release were achieved effectively. All the prepared ISGs comprising CO could expel through the 27-gauge needle for administration by injection and transform into matrix depot after exposure to the simulated gingival crevicular fluid. The antimicrobial activities against Staphylococcus aureus, Escherichia coli, Streptococcus mutans and Porphyromonas gingivalis were increased when the ratio of CO and N-methyl pyrrolidone(NMP) was decreased from 1:1 to 1:10 owing to higher diffusion of DH except that for C. albicans was increased as CO amount was higher.Therefore, CO could minimize the burst while prolonging the drug release of DH-loaded ERS ISG for use as a local drug delivery system for periodontitis treatment.

Comparison of therapeutic effects of topical azithromycin solution and systemic doxycycline on posterior blepharitis

AIM：To compare the effect of azithromycin drop and doxycyciine capsule on treatment of posterior blepharitis.METHODS：Fifty patients（100 eyes） with moderate posterior blepharitis,randomly divided into two therapeutic groups;all the patients got warm eyelid compress and massage three times a day for 3wk.In addition the first group got azithromycin 1% drop,twice daily for 1wk and then one drop daily for 2wk.The second group got oral doxycyciine 100 mg daily for 3wk.At the end of the research,patients＇ signs and symptoms were compared together.ANOVA,Chi-square and MannWhitney tests were used for statistical analysis.RESULTS：Topical therapy with azithromycin and oral therapy with doxycyciine relieved signs and symptoms after 3wk.There were no significant differences between symptoms healing rate and foreign body sensation healing in these two groups（P〉0.05）.However,azithromycin drop was more effective in reduction of eye redness and doxycyciine was more effective in meibomian glands plugging healing and reducing the corneal staining.CONCLUSION：Topical azithromycin could have similar effects as oral doxycyciine on posterior blepharitis in improving subjective symptoms.However,doxycyciine can reduce objective signs such as ocular surface staining and meibomian gland plugging more than azithromycin.

Postoperative multidrug-resistant Acinetobacter baumannii meningitis successfully treated with intravenous doxycycline and intraventricular gentamicin: A case report

BACKGROUND Multidrug-resistant Acinetobacter baumannii(MDRAB) has emerged as an increasingly important pathogen that causes nosocomial meningitis. However,MDRAB-associated nosocomial meningitis is rarely reported in children.CASE SUMMARY We report the case of a 1-year-old girl with a choroid plexus papilloma, who developed postoperative nosocomial meningitis due to MDRAB. The bacterial strain was sensitive only to tigecycline and colistin, and showed varying degrees of resistance to penicillin, amikacin, ceftriaxone, cefixime, cefotaxime,ciprofloxacin, levofloxacin, gentamicin, meropenem, imipenem, and tobramycin.She was cured with intravenous doxycycline and intraventricular gentamicin treatment.CONCLUSION Doxycycline and gentamicin were shown to be effective and safe in the treatment of a pediatric case of MDRAB meningitis.

Determination of Doxycycline by Europium Ion Fluorescence Probe Sensitized by Surfactant

The fluorescence property of europium(Ⅲ)-doxycycline(DC) complex and the effect of reaction condition were studied. It is found that in the buffer solution of Na_2B_4O_7-NaOH at pH 9.63 europium can react with doxycycline to form a complex. After intramolecular energy transfer, the system shows the characteristic fluorescence of Eu 3+. The fluorescence intensity can be enhanced again in addition of non-ionic surfactant Triton X-100 with λ_ ex=375 nm, λ_ em=617 nm. Based on this, a new method using europium ion as fluorescent probe for the determination of trace doxycycline was proposed. The fluorescence intensity is linearly related to the doxycycline concentration in the range of 2.8×10 -6～2.46×10 -5 mol·L -1 with correlation coefficient 0.9973. The detection limit was 1.35×10 -8 mol·L -1. It is applied to the determination of doxycycline in pharmaceutical preparations and in serum satisfactorily. The recovery is within the range of 93%～103%.

STUDIES ON FLUORESCENCE ENHANCING EFFECT AND ALKALINE DEGRADATION MECHANISM OF DOXYCYCLINE AND METHACYCLINE

Degradation reaction of doxycycline or methacycline was carried out in KOH solution and intense fluorescence was obtained.A degradation mechanism of doxycycline or methacycline was suggested.

Bioequivalence Study of Two Oral Doxycycline Formulations (Doxysol^®and Doxymed^®) in Healthy Broiler Chickens

Aims: The present study was designed to assess the comparative bio-equivalence of Doxysol&reg and Doxymed&reg in healthy broiler chickens after oral administration of both products in a dose of 20 mg doxycycline/kg.b.wt. Materials and Methods: Twenty broiler chickens were divided into two groups. The first group was designed to study the pharmacokinetics of Doxysol, while the 2nd group was designed to study the pharmacokinetics of Doxymed. Each broiler chickens in both groups were injected intravenously with 20 mg doxycycline/kg.b.wt. Blood samples were obtained from the wing vein and collected immediately before and at 5, 15, 30 minute, 1, 2, 4, 6, 8, 12 and 24 hours after a single intravenous or oral administration. Results: Doxycycline in both products obeyed a two compartments open model following I.V. injection in a dose of 20 mg/kg.b.wt. The disposition kinetics of Doxysol&reg and Doxymed&reg following oral administration of 20 mg doxycycline base/kg.b.wt. revealed that the maximum blood concentration [Cmax.] were 4.70 and 4.65 μg/ml and attained at [tmax.] of 1.30 and 1.40 hours, respectively. Doxycycline in Doxysol&reg and Doxymed&reg was eliminated with half-lives [t0.5(β)] equal to 1.98 and 2.31 hours, respectively. The mean systemic bioavailability of doxycycline in Doxysol&reg and Doxymed&reg after oral administration in healthy chickens was 92.57 and 88.21%, respectively. Conclusion: Doxymed&reg is bioequivalent to Doxysol&reg since Cmax test/Cmax reference and AUCtest/AUCreference ratios were 99% and 90%, respectively.

Doxycycline Ameliorates Schizophrenia-Like Behaviors in Experimental Models in Mice by Targeting Underlying Oxidative Stress

Current evidences support the inhibition of oxidative and inflammatory signaling mechanisms in the treatment of schizophrenia;as cure for this disease still remains limited. Doxycycline is a tetracycline antibiotic (a minocycline congener) with strong antioxidant and anti-inflammatory properties, and better pharmacokinetic profiles. Preclinical evidence indicates that minocycline possesses antipsychotic properties. This present study was designed to evaluate the effect of doxycycline on schizophrenia-like behaviors, as well as biomarkers of oxidative stress in mice brains. Novelty-induced rearing (NIR) behavior was used to evaluate the tranquilizing effect of doxycycline (25 - 200 mg/kg). The acute antipsychotic effects of doxycycline were assessed using apomorphine-induced stereotypy, ketamine-induced stereotypy, hyperlocomotion and enhanced immobility in forced swim test (FST). Catalepsy test was also employed to evaluate the extrapyramidal adverse effect of doxycycline in mice. The chronic antipsychotic effect of doxycycline was evaluated following oral administration of doxycycline in combination with ketamine (100 mg/kg) intraperitoneally for 10 days. Twenty four hours after the last administration, positive (locomotor activity), cognitive (Y-maze) and negative (FST) symptoms were assessed. Thereafter, levels of biomarkers of oxidative stress were evaluated in mice brains. Doxycycline significantly (P P P < 0.05) prevented the decrease in glutathione, and increased activities of superoxide dismutase and catalase in brain tissues. The results from this study suggest that doxycycline ameliorated schizophrenic-like behaviors via mechanisms related to attenuation of oxidative stress in mouse brain.