-
Scientific Reports Mar 2022The main objective of this study was to determine the cellular and molecular effects of doxycycline on the blood-brain barrier (BBB) and protection against secondary...
The main objective of this study was to determine the cellular and molecular effects of doxycycline on the blood-brain barrier (BBB) and protection against secondary injuries following traumatic brain injury (TBI). Microvascular hyperpermeability and cerebral edema resulting from BBB dysfunction after TBI leads to elevation of intracranial pressure, secondary brain ischemia, herniation, and brain death. There are currently no effective therapies to modulate the underlying pathophysiology responsible for TBI-induced BBB dysfunction and hyperpermeability. The loss of BBB integrity by the proteolytic enzyme matrix metalloproteinase-9 (MMP-9) is critical to TBI-induced BBB hyperpermeability, and doxycycline possesses anti-MMP-9 effect. In this study, the effect of doxycycline on BBB hyperpermeability was studied utilizing molecular modeling (using Glide) in silico, cell culture-based models in vitro, and a mouse model of TBI in vivo. Brain microvascular endothelial cell assays of tight junction protein immunofluorescence and barrier permeability were performed. Adult C57BL/6 mice were subjected to sham versus TBI with or without doxycycline treatment and immediate intravital microscopic analysis for evaluating BBB integrity. Postmortem mouse brain tissue was collected to measure MMP-9 enzyme activity. It was found that doxycycline binding to the MMP-9 active sites have binding affinity of -7.07 kcal/mol. Doxycycline treated cell monolayers were protected from microvascular hyperpermeability and retained tight junction integrity (p < 0.05). Doxycycline treatment decreased BBB hyperpermeability following TBI in mice by 25% (p < 0.05). MMP-9 enzyme activity in brain tissue decreased with doxycycline treatment following TBI (p < 0.05). Doxycycline preserves BBB tight junction integrity following TBI via inhibiting MMP-9 activity. When established in human subjects, doxycycline, may provide readily accessible medical treatment after TBI to attenuate secondary injury.
Topics: Animals; Blood-Brain Barrier; Brain; Brain Injuries, Traumatic; Doxycycline; Humans; Mice; Mice, Inbred C57BL
PubMed: 35354869
DOI: 10.1038/s41598-022-09394-4 -
The Veterinary Quarterly Mar 1993The bioavailability and pharmacokinetics of doxycycline hyclate were determined in calves with immature rumen function. The bioavailability of doxycycline after oral... (Comparative Study)
Comparative Study
The bioavailability and pharmacokinetics of doxycycline hyclate were determined in calves with immature rumen function. The bioavailability of doxycycline after oral administration in a milk replacer was approximately 70%. The elimination half-life of doxycycline was found to be 9.5 +/- 3.0 h. after intravenous administration, and 12.6 +/- 5.0 h. after single oral administration. Plasma concentrations were determined after repeated oral administration of doxycycline dissolved in a milk replacer, at a dose of 5 mg per kg body weight, twice daily. During the period of administration, the plasma concentrations varied between Cmin of 1.0 +/- 0.19 mg/L and Cmax of 2.3 +/- 0.19 mg/L.
Topics: Administration, Oral; Animals; Biological Availability; Cattle; Doxycycline; Half-Life; Injections, Intravenous; Male; Pharmaceutical Vehicles; Rumen
PubMed: 8498009
DOI: 10.1080/01652176.1993.9694358 -
Drugs of Today (Barcelona, Spain : 1998) Jan 2007Approximately 13 million individuals in the United Sates suffer from rosacea, a recurrent disease that may require long-term therapy. Topical and oral antibiotics have... (Review)
Review
Approximately 13 million individuals in the United Sates suffer from rosacea, a recurrent disease that may require long-term therapy. Topical and oral antibiotics have been used to treat rosacea; however, high-dose antibiotics or long-term, low-dose antibiotics commonly used for the treatment of rosacea flares or for rosacea maintenance therapy, respectively, can lead to the development of antibiotic-resistant organisms. The first oral medication approved by the U.S. Food and Drug Administration for the treatment of rosacea in the United States is Oracea (CollaGenex Pharmaceuticals Inc., Newtown, PA, USA). Oracea is a 40 mg capsule of doxycycline monohydrate, containing 30 mg immediate-release and 10 mg delayed-release doxycycline beads ("anti-inflammatory-dose doxycycline"). Anti-inflammatory-dose doxycycline is not an antibiotic and does not lead to the development of antibiotic-resistant organisms. Each capsule of anti-inflammatory-dose doxycycline contains a total of 40 mg of anhydrous doxycycline as 30 mg of immediate-release and 10 mg of delayed-release beads. In contrast to other oral therapies, anti-inflammatory-dose doxycycline is taken once daily, which may increase treatment compliance. The results of two phase III trials have been encouraging, leading to the recent release (summer 2006) of Oracea for the treatment of rosacea in the United States. Anti-inflammatory-dose doxycycline should not be used by individuals with known hypersensitivity to tetracyclines or increased photosensitivity, or by pregnant or nursing women (anti-inflammatory-dose doxycycline is a pregnancy category-D medication). The risk of permanent teeth discoloration and decreased bone growth rate make anti-inflammatory-dose doxycycline contraindicated in infants and children. However, when used appropriately in patients with rosacea, anti-inflammatory-dose doxycycline may help prolong the effectiveness and life span of our most precious antibiotics.
Topics: Anti-Bacterial Agents; Doxycycline; Drug Resistance; Female; Humans; Male; Patient Compliance; Rosacea; Skin
PubMed: 17315050
DOI: 10.1358/dot.2007.43.1.1025697 -
European Journal of Pharmacology Feb 2022Colorectal cancer (CRC) is considered the second most frequent cancer globally and one of the deadliest malignancies in humans. On the other hand, over time and facing... (Review)
Review
Colorectal cancer (CRC) is considered the second most frequent cancer globally and one of the deadliest malignancies in humans. On the other hand, over time and facing the challenges of cancer treatment, several therapeutic approaches, including surgery, radiotherapy, chemotherapy, and immunotherapy, are being developed. Evidence showed that combination therapies had given relatively satisfactory clinical outcomes in inhibiting tumor progression and increasing patient survival compared with monotherapy. Among the available compounds and drugs used in chemotherapy, doxycycline, an antimicrobial drug, has been suitable for treating several malignancies such as CRC. It has been revealed that doxycycline has anti-tumor properties and can help control tumor growth in various mechanisms, such as inhibiting anti-apoptotic and angiogenic proteins. In addition, studies have shown that combination therapy with doxycycline and other anti-tumor drugs, such as doxorubicin, anti-angiogenic factors, and anti-check-point blockers, can inhibit tumor progression. Therefore, this review summarized the anti-tumor mechanisms of doxycycline in CRC treatment and related combination therapies.
Topics: Antineoplastic Agents; Colorectal Neoplasms; Combined Modality Therapy; Doxycycline; Humans; Immunotherapy
PubMed: 34973952
DOI: 10.1016/j.ejphar.2021.174593 -
The Journal of Antimicrobial... Oct 2017The use of doxycycline has been avoided before 8 years of age due to known dental staining caused by tetracyclines, although doxycycline differs from classical...
BACKGROUND
The use of doxycycline has been avoided before 8 years of age due to known dental staining caused by tetracyclines, although doxycycline differs from classical tetracyclines in many ways. Doxycycline is still an important antimicrobial agent, but its dental safety is not well studied.
OBJECTIVES
To examine the state of permanent teeth after doxycycline exposure in children <8 years of age.
METHODS
Details of doxycycline treatment were collected from medical records. After the eruption of permanent teeth the dental status was examined by an experienced paediatric dentist for detection of dental staining and enamel hypoplasia. The resulting dental photographs were evaluated by a second independent experienced paediatric dentist.
RESULTS
The mean age of 38 study subjects at the time of doxycycline treatment was 4.7 years (range 0.6-7.9 years, SD 2.3). The doxycycline dose was 10 mg/kg/day (varying from 8 to 10 mg/kg/day) for the first 2-3 days and 5 mg/kg/day (varying from 2.5 to 10 mg/kg/day) thereafter. The mean length of the treatment was 12.5 days (SD 6.0) and ranged from 2 to 28 days. Tetracycline-like staining or enamel hypoplasia of developing teeth was detected in none of the subjects.
CONCLUSIONS
Doxycycline treatment of small children does not seem to induce permanent tooth staining.
Topics: Anti-Bacterial Agents; Child; Child, Preschool; Doxycycline; Female; Humans; Infant; Male; Medical Records; Tooth; Tooth Discoloration
PubMed: 29091225
DOI: 10.1093/jac/dkx245 -
AAPS PharmSciTech Feb 2024This study explores a novel approach to address the challenges of delivering highly water-soluble drug molecules by employing hydrophobic ion-pairing (HIP) complexes...
This study explores a novel approach to address the challenges of delivering highly water-soluble drug molecules by employing hydrophobic ion-pairing (HIP) complexes within poly (lactic-co-glycolic acid) (PLGA) microspheres. The HIP complex, formed between doxycycline hyclate (DH) and docusate sodium (DS), renders the drug hydrophobic. The development of the microspheres was done using the QbD approach, namely, Box-Behnken Design (BBD). A comprehensive characterization of the HIP complex confirmed the successful conversion of DH. DH and the HIP complex were effectively loaded into PLGA microspheres using the oil-in-water (O/W) emulsion solvent evaporation method. Results demonstrated significant improvements in percentage entrapment efficiency (% EE) and drug loading (% DL) for DH within the HIP complex-loaded PLGA microspheres compared to DH-loaded microspheres alone. Additionally, the initial burst release of DH reduced to 3% within the initial 15 min, followed by sustained drug release over 8 days. The modified HIP complex strategy offers a promising platform for improving the delivery of highly water-soluble small molecules. It provides high % EE, % DL, minimal initial burst release, and sustained release, thus having the potential to enhance patient compliance and drug delivery efficiency.
Topics: Humans; Polylactic Acid-Polyglycolic Acid Copolymer; Polyglycolic Acid; Drug Liberation; Lactic Acid; Doxycycline; Microspheres; Water; Emulsions; Particle Size
PubMed: 38424393
DOI: 10.1208/s12249-024-02760-7 -
European Journal of Pharmaceutical... Dec 2015Doxycicline is used in dogs as treatment of several bacterial infections, mycoplasma, chlamydia and rickettsial diseases. However, it requires long treatments and... (Comparative Study)
Comparative Study Randomized Controlled Trial
Doxycicline is used in dogs as treatment of several bacterial infections, mycoplasma, chlamydia and rickettsial diseases. However, it requires long treatments and several doses to be effective. The aim of this study was to determine the pharmacokinetics of four formulations of doxycycline hyclate, administered orally, with different proportions of excipients, acrylic acid-polymethacrylate-based matrices, to obtain longer therapeutic levels than conventional formulation. Forty-eight dogs were randomly assigned in five groups to receive a single oral dose (20mg/kg) of doxycycline hyclate without excipients (control) or a long-acting formulation containing doxycycline, acrylic acid polymer, and polymethacrylate in one of the following four proportions: DOX1(1:0.25:0.0035), DOX2(1:0.5:0.0075), DOX3 (1:1:0.015), or DOX4(1:2:0.0225). Temporal profiles of serum concentrations were obtained at several intervals after each treatment. Therapeutic concentrations were observed for 60h for DOX1 and DOX4, 48h for DOX2 and DOX3 and only 24h for DOX-C. None of the pharmacokinetic parameter differed significantly between DOX1 and DOX2 or between DOX3 and DOX4; however, the findings for the control treatment were significantly different compared to all four long-acting formulations. Results indicated that DOX1 had the most adequate pharmacokinetic-pharmacodynamic relationships for a time-dependent drug and had longer release times than did doxycycline alone. However, all four formulations can be effective depend on the minimum effective serum doxycycline concentration of the microorganism being treated. These results suggest that the use of any of these formulations can reduce the frequency of administration, the patient's stress, occurrence of adverse effects and the cost of treatment.
Topics: Administration, Oral; Animals; Anti-Bacterial Agents; Cross-Over Studies; Delayed-Action Preparations; Dogs; Doxycycline; Female; Male
PubMed: 26393684
DOI: 10.1016/j.ejps.2015.09.012 -
Journal of the American Veterinary... Feb 2019OBJECTIVE To compare improvements in values for periodontal disease indices in dogs following treatment with closed root planing (CRP) alone, CRP with concurrent 8.5%...
Comparison of closed root planing with versus without concurrent doxycycline hyclate or clindamycin hydrochloride gel application for the treatment of periodontal disease in dogs.
OBJECTIVE To compare improvements in values for periodontal disease indices in dogs following treatment with closed root planing (CRP) alone, CRP with concurrent 8.5% doxycycline hyclate gel application, and CRP with concurrent 2% clindamycin hydrochloride reverse-polymer hydrogel application. DESIGN Randomized, blinded, controlled clinical trial. ANIMALS 34 client-owned dogs with periodontal pockets measuring 3.5 to 5.5 mm deep. PROCEDURES Dogs were randomly assigned to receive 1 of 3 treatments: CRP alone (n = 10) or CRP plus 8.5% doxycycline hyclate (12) or 2% clindamycin hydrochloride (12) gel applied within the periodontal pockets. Indices of periodontal disease severity were recorded before and 12 weeks after treatment, and outcomes were compared among treatment groups. RESULTS Except for gingivitis index, no significant differences were identified among the 3 treatment groups in the amount of improvement observed in values for periodontal disease indices following treatment. A minor but clinically unimportant improvement in mean gingivitis index values was identified for dogs treated with CRP plus doxycycline gel, which differed significantly from improvements in the other 2 groups. Teeth that were initially more severely affected (pocket depths, 5.0 to 5.5 mm) had the greatest amount of improvement, whereas teeth with only mildly high initial pocket depths (3.5 to 4.0 mm) had less improvement. CONCLUSIONS AND CLINICAL RELEVANCE Overall, addition of doxycycline or clindamycin gel application to CRP for the treatment of periodontal disease in dogs yielded no clinically relevant benefit over CRP during the 12-week follow-up period.
Topics: Administration, Topical; Animals; Anti-Bacterial Agents; Clindamycin; Dog Diseases; Dogs; Doxycycline; Periodontal Diseases; Root Planing; Treatment Outcome
PubMed: 30668243
DOI: 10.2460/javma.254.3.373 -
Canadian Journal of Veterinary Research... Jan 1988Six adult dogs were given doxycycline hyclate at a dosage of 5 mg/kg of body weight intravenously so that pharmacokinetic parameters could be evaluated. Serum...
Six adult dogs were given doxycycline hyclate at a dosage of 5 mg/kg of body weight intravenously so that pharmacokinetic parameters could be evaluated. Serum doxycycline concentrations were determined over a 48 h period using a modified agar well bioassay. Compartmental pharmacokinetic evaluation of the serum concentration time data indicated that doxycycline has a half-life of 10.36 h, a body clearance of 1.68 +/- 0.44 mL/min/kg, and a volume of distribution at steady state of 1.468 +/- 0.237 L/kg. Doxycycline pharmacokinetics are favorable for therapeutic use in the dog.
Topics: Animals; Dogs; Doxycycline; Female; Injections, Intravenous; Male; Microcomputers; Software
PubMed: 3349389
DOI: No ID Found -
Cornea Sep 1993We examined the effects of doxycycline hyclate on epithelial healing in vivo in the rabbit alkali-burn model. Twelve 2-3-kg Dutch belted rabbits were divided into three...
We examined the effects of doxycycline hyclate on epithelial healing in vivo in the rabbit alkali-burn model. Twelve 2-3-kg Dutch belted rabbits were divided into three groups and received standard bilateral alkali burns (1 N sodium hydroxide for 30 s in an 11-mm circular plastic well). In group 1, two rabbits (four eyes) served as untreated controls. In group 2, five rabbits (10 eyes) received doxycycline hyclate (1.5 mg/kg) orally daily for 14 days. In group 3, five rabbits (10 eyes) received doxycycline hyclate (5 mg/kg) orally daily for 14 days. The epithelial defects were drawn and photographed on alternate days, after fluorescein staining. At conclusion, extracts of the corneas were evaluated for collagenase activity. At 14 days, the mean percentage of epithelial defects results in groups 1-3 were 50.0, 50.7, and 7.1%, respectively. Using the Wilcoxon rank sum test (two tailed), the differences were found to be statistically significant (p = 0.0015). Preliminary data indicated that oral doxycycline administration also decreased the collagenase activity in corneas obtained from these animals. Our preliminary findings indicated that systematically administered doxycycline hyclate, 5 mg/kg/day, promotes corneal reepithelialization in the rabbit alkali-burn model, a result, perhaps, of the drug's ability to inhibit excessive collagenase activity.
Topics: Administration, Oral; Animals; Burns, Chemical; Cell Division; Collagenases; Cornea; Corneal Injuries; Disease Models, Animal; Doxycycline; Epithelium; Eye Burns; Female; Male; Rabbits; Sodium Hydroxide; Wound Healing
PubMed: 8306657
DOI: 10.1097/00003226-199309000-00002