Oral doxycycline pharmacokinetics: Lambs in comparison with sheep.

The pharmacokinetics of doxycycline was investigated in lactating sheep and lambs after oral administration at a dose of 10 mg/kg. Concentrations in plasma and milk were assayed with HPLC-PDA analysis. Doxycycline penetrates into the milk, and levels (0.38 ± 0.21 µg/ml) were found 0.5 hr after the treatment. The results suggest that the lambs can be exposed to doxycycline by suckling milk from their treated mothers. Population pharmacokinetic analysis showed a positive relationship between age, which reflects the stage of development of rumen function, and clearance. Possible explanations for the observed differences include the undeveloped rumen in lambs, the differences in the feed and liver function as evidenced by the blood biochemical parameters aspartate aminotransferase (AST) and alanine aminotransferase (ALT), which were significantly lower in lambs (62.67 ± 27.83 U/L and 8.50 ± 6.80 U/L) than in sheep (114.33 ± 20.77 U/L and 18.00 ± 3.16 U/L).

Colorimetric detection of serum doxycycline with d-histidine-functionalized gold nanoclusters as nanozymes.

Gold nanoclusters (AuNCs) have emerged as a new generation of "nanozymes" based on their intrinsic catalytic activity. However, highly selective and colorimetric detection of drugs is still far from adequately developed due to the lack of means of regulating the catalytic activity of nanozymes. Herein, d-histidine stabilized AuNCs (d-His@AuNCs) were synthesized and their nanozyme ability was demonstrated in the catalytic oxidation of the peroxidase substrate, 3,3',5,5'-tetramethylbenzidine, for the promotion of hydrogen peroxide. Copper ions led to the aggregation of d-His@AuNCs and inhibited their peroxidase-like activity. The addition of doxycycline restored the enzyme-mimicking catalytic activity of d-His@AuNCs, which was based on the strong coordination interaction between copper ions and doxycycline. A highly sensitive and colorimetric assay for determining the amount of doxycycline was developed at a detection wavelength of 650 nm. The color intensity and ultraviolet-visible absorbance intensity of the testing assay displayed a good linear relationship in the doxycycline concentration range of 5.0-12.5 µM, with a limit of detection of 1.0 µM. Moreover, the metabolic process of doxycycline in serum was further investigated with the proposed monitoring system after the drug was abdominally injected into rats. Notably, the tunable catalytic activity performance of the nanozymes indicates their significant potential in clinical application.

Tissue residue depletion kinetics and withdrawal time estimation of doxycycline in grass carp, Ctenopharyngodon idella, following multiple oral administrations.

This study aimed to determine the plasma and tissue residue depletion kinetics of doxycycline (DC) in grass carp (Ctenopharyngodon idella) after daily oral administrations at 20 mg/kg for 3 days, and to calculate the corresponding withdrawal times. Following drug administrations, samples of plasma, liver, kidney, gill and muscle + skin were collected at predetermined time points (0.25, 0.5, 1, 3, 5, 7, 14, 21, 28, 35, 42, 49 and 56 days) and analyzed for concentrations of DC using a LC-MS/MS method. The results showed that liver had the highest concentrations and the slowest depletion compared to other tissues, with detectable DC up to 49 days (58.9 ± 12.8 µg/kg). The WT 1.4 software and "reschem" package were used to calculate withdrawal times, and the results were similar. The results suggest a withdrawal time of 41 days for Europe and China and 50 days for Japan is needed for DC in grass carp after 3 daily oral administrations at 20 mg/kg. Overall, this study improves our understanding of the tissue residue depletion kinetics of DC in fish, and the results may help regulatory agencies to determine proper withdrawal periods based on different regulatory standards in different countries to ensure safety of aquatic food products.

Toxicity and Safety Study of D-PLEX100 in a Sternal Surgical Defect in New Zealand White Rabbits.

Bacterial infections are a common complication after surgical procedures. Therefore, local delivery of antibiotics has been developed, including the use of biodegradable polymers. A newly developed product for prevention of surgical site infections is a polymer-lipid encapsulation matrix loaded with doxycycline, named D-PLEX100 (D-PLEX). We evaluated the toxicity and safety of D-PLEX using a sternal surgical defect model in rabbits. D-PLEX was tested with three different concentrations of doxycycline in comparison to sham-operated control after administration into the sternal surgical defect and on the ventral side of the sternum in New Zealand White (NZW) rabbits, following 15 months of exposure. No mortality or abnormal clinical findings were attributed to D-PLEX, and clinical pathology assays were normal. Histological examinations revealed no treatment-related adverse findings in any of the examined tissues, including the osseous and surrounding soft tissues. It has been shown that D-PLEX gradually degraded until complete disappearance after 9 months, and mainly during the first 3 months, in parallel to normal bone formation. In addition, the administration of D-PLEX did not affect sternal bone strength. This study adds to the growing data on preclinical safety studies utilizing biodegradable materials and provides information on the expected normal reaction to biodegradable materials in the sternum of NZW rabbits.

New HPLC-MS method for rapid and simultaneous quantification of doxycycline, diethylcarbamazine and albendazole metabolites in rat plasma and organs after concomitant oral administration.

A sensitive and relatively fast, cost-effective high-performance liquid chromatographic method coupled with mass spectrometer (HPLC-MS) is herein reported for the first time for a simultaneous quantification of plasma and organs concentration of three therapeutic agents that are widely used in treatment of lymphatic filariasis (LF), namely, doxycycline (DOX), diethylcarbamazine (DEC) and albendazole (ABZ) metabolites. The method was developed and validated as per ICH and FDA guidelines and successfully employed to quantify DOX, DEC and ABZ metabolites (albendazole sulfoxide (ABZ-OX) and albendazole sulfone (ABZ-ON)) in the plasma and organs of Sprague Dawley rats after oral concomitant administration of the above mentioned therapeutic agents. Importantly, a simple, one-step protein precipitation and extraction method was used to extract the four compounds efficiently with a recovery in the range of 79.88 ± 5.02%-90.71 ± 5.13%, 85.72 ± 7.22%-93.17 ± 5.55%, 94.38 ± 7.35%-101.00 ± 8.88% and 94.38 ± 7.35%-99.87 ± 10.22% in plasma and organs for DOX, DEC, ABZ-OZ and ABZ-ON, respectively. Separation of all analytes was performed on a Xselect CSH™ C18 HPLC column (Waters, 3.0 x 150 mm, 3.5 µm particle size) with gradient elution employing a mobile phase consisting of 0.1% v/v formic acid in water and methanol with a run time of 20 min. Quantification was carried out employing a single, quadruple MS detector operated with single ion monitoring (SIM) mode and the ion transitions at m/z of 445.4, 200.2, 282.3 and 298.3 for DOX, DEC, ABZ-OX and ABZ-ON respectively. The MS response for plasma samples was linear across the concentration range of 2.5-2500 ng/mL for DOX, 0.5-500 ng/mL for DEC, 1-1000 ng/mL for ABZ-OX and ABZ-ON with a correlation coefficient (r2) ≥ 0.998. The method was selective, precise and accurate. This method allowed us to get an insight into the pharmacokinetics and biodistribution of the three therapeutic agents after simultaneous oral administration to Sprague Dawley rats. This bioanalytical method could provide a reliable, reproducible and excellent tool for routine therapeutic drug monitoring of the above mentioned therapeutic agents and also support other clinical pharmacokinetic-based studies.

Plasma and Brain Concentrations of Doxycycline after Single and Repeated Doses in Wild-Type and APP23 Mice.

Repurposing doxycycline for the treatment of amyloidosis has recently been put forward because of the antiaggregating and anti-inflammatory properties of the drug. Most of the investigations of the therapeutic potential of doxycycline for neurodegenerative amyloidosis, e.g., prion and Alzheimer disease (AD), have been carried out in mouse models, but surprisingly no data are available regarding the concentrations reached in the brain after systemic administration. We filled this gap by analyzing the pharmacokinetic profile of doxycycline in plasma and brain after single and repeated intraperitoneal injections of 10 and 100 mg/kg, in wild-type mice and the APP23 mouse model of AD. The main outcomes of our study are: 1) Peak plasma concentrations ranged from 2 to10 µg/ml, superimposable to those in humans; 2) brain-to-plasma ratio was ∼0.2, comparable to the cerebrospinal fluid/serum ratios in humans; 3) brain Cmax 4-6 hours after a single dose was ∼0.5 (10 mg/kg) and ∼5 µM (100 mg/kg). Notably, these concentrations are lower than those required for the drug's antiaggregating properties as observed in cell-free studies, suggesting that other features underlie the positive cognitive effects in AD mice; 4) elimination half-life was shorter than in humans (3-6 vs. 15-30 hours), therefore no significant accumulation was observed in mouse brain following repeated treatments; and 5) there were no differences between doxycycline concentrations in brain areas of age-matched wild-type and APP23 mice. These data are useful for planning preclinical studies with translational validity, and to identify more reliably the mechanism(s) of action underlying the central in vivo effects of doxycycline.

A multifunctional molecularly imprinted polymer-based biosensor for direct detection of doxycycline in food samples.

In this study, we developed a new type of multifunctional molecularly imprinted polymer (MIP) composite as an all-in-one biosensor for the low-cost, rapid and sensitive detection of doxycycline in pig plasma. The MIP composite consisted of a magnetic core for ease of manipulation, and a shell of fluorescent MIPs for selective recognition of doxycycline. By simply incorporating a small amount of fluorescent monomer (fluorescein-O-acrylate), the fluorescent MIP layer was successfully grafted onto the magnetic core via a surface imprinting technique. The resultant MIP composites showed significant doxycycline-dependent fluorescence quenching in an aqueous environment. Good linearity ranging from 0.2 to 6 µM was achieved, and the limit of detection was determined to be 117 nM. The biosensor also showed good selectivity towards doxycycline when compared to other common antibiotic residues. The multifunctional MIP composites were used to directly extract doxycycline from spiked pig plasma samples and quantify the antibiotics based on the quenched fluorescence signals. Recoveries of doxycycline were found in the range of 88-107%.

The effect of measuring serum doxycycline concentrations on clinical outcomes during treatment of chronic Q fever.

Background: First choice treatment for chronic Q fever is doxycycline plus hydroxychloroquine. Serum doxycycline concentration (SDC) >5 µg/mL has been associated with a favourable serological response, but the effect on clinical outcomes is unknown. Objectives: To assess the effect of measuring SDC during treatment of chronic Q fever on clinical outcomes. Methods: We performed a retrospective cohort study, to assess the effect of measuring SDC on clinical outcomes in patients treated with doxycycline and hydroxychloroquine for chronic Q fever. Primary outcome was the first disease-related event (new complication or chronic Q fever-related mortality); secondary outcomes were all-cause mortality and PCR-positivity. Multivariable analysis was performed with a Cox proportional hazards model, with shared-frailty terms for different hospitals included. Results: We included 201 patients (mean age 68 years, 83% male): in 167 patients (83%) SDC was measured, 34 patients (17%) were treated without SDC measurement. First SDC was >5 µg/mL in 106 patients (63%), all with 200 mg doxycycline daily. In patients with SDC measured, dosage was adjusted in 41% (n = 68), concerning an increase in 64 patients. Mean SDC was 4.1 µg/mL before dosage increase, and 5.9 µg/mL afterwards. SDC measurement was associated with a lower risk for disease-related events (HR 0.51, 95% CI 0.26-0.97, P = 0.04), but not with all-cause mortality or PCR-positivity. Conclusions: SDC measurement decreases the risk for disease-related events, potentially through more optimal dosing or improved compliance. We recommend measurement of SDC and striving for SDC >5 µg/mL and <10 µg/mL during treatment of chronic Q fever.

Simultaneous UHPLC-UV analysis of hydroxychloroquine, minocycline and doxycycline from serum samples for the therapeutic drug monitoring of Q fever and Whipple's disease.

A fast UHPLC-UV method was developed for the simultaneous analysis of Hydroxychloroquine, Minocycline and Doxycycline drugs from 100µL of human serum samples. Serum samples were extracted by liquid-liquid extraction and injected into a phenyl hexyl reverse phase column. Compounds were separated using a mobile phase linear gradient and monitored by UV detection at 343nm. Chloroquine and Oxytetracycline were used as internal standards. Lower and upper limits of quantifications, as well as the other levels of calibration, were validated with acceptable accuracy (<15% deviation) and precision (<15% coefficient of variation) according to the European Medicines Agency guidelines. This new method enables cost and time reduction and was considered suitable for the clinical laboratory. It is the first published assay for the therapeutic drug monitoring of patients diagnosed with Q fever or Whipple's disease.

Systemic antibiotic prophylaxis prior to gastrointestinal surgery - is oral administration of doxycycline and metronidazole adequate?

BACKGROUND: Antibiotic prophylaxis is recommended prior to a wide range of gastrointestinal operations to reduce the rate of surgical site infections (SSIs). Traditional intravenous (IV) drugs are costly and their preparation strains nursing resources at the wards. While oral administration may attenuate these limitations, its use remains limited. We aimed to assess whether a dual oral antibiotic prophylaxis regimen provides adequate serum concentrations throughout the surgical procedure. METHODS: We measured serum concentrations of doxycycline and metronidazole following single oral doses of 400 mg doxycycline and 1200 mg metronidazole at first incision and repeated at wound closure in a cohort of patients undergoing elective gastrointestinal surgery. Both drugs were dispensed at least two hours before skin incision. Serum concentrations were compared to minimum inhibitory concentrations (MIC) and epidemiological cut-off values (ECOFFs) for relevant pathogens. RESULTS: Mean serum concentrations of doxycycline at first incision and at wound closure were 5.75 mg/L and 4.66 mg/L and of metronidazole 18.88 mg/L and 15.56 mg/L, respectively. Metronidazole concentrations were above ECOFF (2 mg/L) for relevant anaerobic species in 103/104 of patients in both samples. Doxycycline serum concentrations were above the ECOFF for common Enterobacteriaceae species (4 mg/L) in both samples in 58/104 patients (55.8%). CONCLUSIONS: A single dose of orally administered metronidazole provides adequate concentrations throughout surgery in a heterogeneous cohort of patients. Uncertainty persists regarding the adequacy of doxycycline concentrations, as the optimal serum level of doxycycline in a prophylactic setting has not been established.

Population Pharmacokinetic Model of Doxycycline Plasma Concentrations Using Pooled Study Data.

The literature presently lacks a population pharmacokinetic analysis of doxycycline. This study aimed to develop a population pharmacokinetic model of doxycycline plasma concentrations that could be used to assess the power of bioequivalence between Doryx delayed-release tablets and Doryx MPC. Doxycycline pharmacokinetic data were available from eight phase 1 clinical trials following single/multiple doses of conventional-release doxycycline capsules, Doryx delayed-release tablets, and Doryx MPC under fed and fasted conditions. A population pharmacokinetic model was developed in a stepwise manner using NONMEM, version 7.3. The final covariate model was developed according to a forward inclusion (P < 0.01) and then backward deletion (P < 0.001) procedure. The final model was a two-compartment model with two-transit absorption compartments. Structural covariates in the base model included formulation effects on relative bioavailability (F), absorption lag (ALAG), and the transit absorption rate (KTR) under the fed status. An absorption delay (lag) for the fed status (FTLAG2 = 0.203 h) was also included in the model as a structural covariate. The fed status was observed to decrease F by 10.5%, and the effect of female sex was a 14.4% increase in clearance. The manuscript presents the first population pharmacokinetic model of doxycycline plasma concentrations following oral doxycycline administration. The model was used to assess the power of bioequivalence between Doryx delayed-release tablets and Doryx MPC, and it could potentially be used to critically examine and optimize doxycycline dose regimens.

Metabolomic profiling of doxycycline treatment in chronic obstructive pulmonary disease.

Serum metabolic profiling can identify the metabolites responsible for discrimination between doxycycline treated and untreated chronic obstructive pulmonary disease (COPD) and explain the possible effect of doxycycline in improving the disease conditions. 1H nuclear magnetic resonance (NMR)-based metabolomics was used to obtain serum metabolic profiles of 60 add-on doxycycline treated COPD patients and 40 patients receiving standard therapy. The acquired data were analyzed using multivariate principal component analysis (PCA), partial least-squares-discriminant analysis (PLS-DA), and orthogonal projection to latent structure with discriminant analysis (OPLS-DA). A clear metabolic differentiation was apparent between the pre and post doxycycline treated group. The distinguishing metabolites lactate and fatty acids were significantly down-regulated and formate, citrate, imidazole and l-arginine upregulated. Lactate and folate are further validated biochemically. Metabolic changes, such as decreased lactate level, inhibited arginase activity and lowered fatty acid level observed in COPD patients in response to add-on doxycycline treatment, reflect the anti-inflammatory action of the drug. Doxycycline as a possible therapeutic option for COPD seems promising.

Stability of Doxycycline in Feed and Water and Minimal Effective Doses in Tetracycline-Inducible Systems.

Despite the extensive use of doxycycline in tetracycline-inducible rodent models, little is known regarding its stability in feed or water or the most effective route or dose. We assessed the concentrations of doxycycline in reverse-osmosis-purified (RO; pH 6.0) and acidified RO (pH 2.6) water in untinted or green-tinted bottles. Doxycycline remained stable in all groups for 7 d and in acidified water in untinted bottles for 14 d. Fungal growth occurred in nonacidified water in tinted and untinted bottles by 12 and 14 d, respectively, and in tinted bottles containing acidified water on day 14, but not in untinted bottles with acidified water. Doxycycline concentrations were also assessed before and at various points after the pelleting of feed from 2 vendors. Each batch was divided for storage at 4 °C, at room temperature, or within ventilated mouse isolator cages and then sampled monthly for 6 mo. Drying caused the greatest decline in doxycycline concentration, whereas γ-irradiation plus shipping and storage condition had minimal effect. Two mouse lines with tetracycline-inducible promoters received 25, 150, or 467 µg/mL or 2 mg/mL doxycycline in water and 200 or 625 ppm in feed before analysis of GFP expression. GFP was expressed in Rosa-rtTA2 mice at 150 µg/mL, whereas Cags-rtTA3 mice required 25 µg/mL. These studies indicate that 1) doxycycline-compounded feed can be handled in the same manner as standard rodent feed, 2) tinted water bottles are not necessary for maintaining drug concentrations, and 3) concentrations lower than those used typically may be effective in lines with tetracycline-inducible promoters.

A rapid and sensitive assay for determination of doxycycline using thioglycolic acid-capped cadmium telluride quantum dots.

A rapid, simple and inexpensive spectrofluorimetric sensor for determination of doxycycline based on its interaction with thioglycolic acid-capped cadmium telluride quantum dots (TGA/CdTe QDs) has been developed. Under the optimum experimental conditions, the sensor exhibited a fast response time of <10s. The results revealed that doxycycline could quench the fluorescence of TGA/CdTe QDs via electron transfer from the QDs to doxycycline through a dynamic quenching mechanism. The sensor permitted determination of doxycycline in a concentration range of 1.9×10(-6)-6.1×10(-5)molL(-1) with a detection limit of 1.1×10(-7)molL(-1). The sensor was applied for determination of doxycycline in honey and human serum samples.

Comparative pharmacokinetics of a new oral long-acting formulation of doxycycline hyclate: A canine clinical 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.

In vitro and in vivo Evaluation of Synergism between Anti-Tubercular Spectinamides and Non-Classical Tuberculosis Antibiotics.

Spectinamides are new semi-synthetic spectinomycin derivatives with potent anti-tubercular activity. The reported synergism of the precursor spectinomycin with other antibiotics prompted us to examine whether spectinamides sensitize M. tuberculosis to other antibiotics not traditionally used in the treatment of tuberculosis to potentially expand therapeutic options for MDR/XDR Tuberculosis. Whole cell synergy checkerboard screens were performed using the laboratory strain M. tuberculosis H37Rv, lead spectinamide 1599, and a broad panel of 27 antibiotics. In vitro, 1599 synergized with 11 drugs from 6 antibiotic classes. The observed synergy was tested against clinical isolates confirming synergy with Clarithromycin, Doxycycline and Clindamycin, combinations of which were taken forward for in vivo efficacy determination. Co-administration of 1599 and clarithromycin provided additional bacterial killing in a mouse model of acute tuberculosis infection, but not in a chronic infection model. Further studies indicated that mismatched drug exposure profiles likely permitted induction of phenotypic clarithromycin resistance and subsequent loss of synergism. These studies highlight the importance of validating in vitro synergism and the challenge of matching drug exposures to obtain a synergistic outcome in vivo. Results from this study indicate that a 1599 clarithromycin combination is potentially viable, providing the drug exposures can be carefully monitored.

Doxycycline assay hair samples for testing long-term compliance treatment.

OBJECTIVES: Many patients undergoing long-term doxycycline treatment do not regularly take their treatment because of photosensitivity. Our objective was to create an assay for determining doxycycline levels and to use hair samples for monitoring the compliance over a longer period of time. METHODS: We tested sera and hair samples from patients treated with doxycycline by a suitable ultra-high performance liquid chromatography (UHPLC) based assay. RESULTS: We estimated that the speed of hair growth is roughly 1.25 cm per month and we were able to determine doxycycline levels over a 6-month period. We tested 14 patients treated with doxycycline and we found similar levels of doxycycline in the serum and the hair samples representing the last 4 months. Linear regression analysis revealed that the level of doxycycline in the serum remained stable over time (p = 0.7) but the level of doxycycline in the hair decreased significantly over time (p = 0.03) indicating a degradation of this molecule in the hair. We detected two patients who did not have antibiotic in the hair, indicating a lack of compliance that was also confirmed by interview. CONCLUSION: Hair samples can be used to test long-term compliance in patients to explain failures or relapses.

Pharmacokinetics of an oral extended-release formulation of doxycycline hyclate containing acrylic acid and polymethacrylate in dogs.

OBJECTIVE: To determine the pharmacokinetics of doxycycline hyclate administered orally in the form of experimental formulations with different proportions of acrylic acid-polymethacrylate-based matrices. ANIMALS: 30 healthy adult dogs. PROCEDURES: In a crossover study, dogs were randomly assigned (in groups of 10) to receive a single oral dose (20 mg/kg) of doxycycline hyclate without excipients (control) or extended-release formulations (ERFs) containing doxycycline, acrylic acid polymer, and polymethacrylate in the following proportions: 1:0.5:0.0075 (ERF1) or 1:1:0.015 (ERF2). Serum concentrations of doxycycline were determined for pharmacokinetic analysis before and at several intervals after each treatment. RESULTS: Following oral administration to the study dogs, each ERF resulted in therapeutic serum doxycycline concentrations for 48 hours, whereas the control treatment resulted in therapeutic serum doxycycline concentrations for only 24 hours. All pharmacokinetic parameters for ERF1 and ERF2 were significantly different; however, findings for ERF1 did not differ significantly from those for the control treatment. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that both ERFs containing doxycycline, acrylic acid polymer, and polymethacrylate had an adequate pharmacokinetic-pharmacodynamic relationship for a time-dependent drug and a longer release time than doxycycline alone following oral administration in dogs. Given the minimum effective serum doxycycline concentration of 0.26 µg/mL, a dose interval of 48 hours can be achieved for each tested ERF. This minimum inhibitory concentration has the potential to be effective against several susceptible bacteria involved in important infections in dogs. Treatment of dogs with either ERF may have several benefits over treatment with doxycycline alone.

Doxycycline levels and anti-Wolbachia antibodies in sera from dogs experimentally infected with Dirofilaria immitis and treated with a combination of ivermectin/doxycycline.

Sera from Dirofilaria immitis-experimentally infected dogs treated with a combination of ivermectin/doxycycline were analysed for doxycycline levels by HPLC and anti-Wolbachia Surface Protein (rWSP) antibodies by ELISA and compared with sera from dogs treated with doxycycline alone. Results show that doxycycline levels were not statistically different between the two groups. Circulating anti-WSP antibody titres were markedly lower in both treatment groups when compared to control D. immitis infected dogs, indicating that doxycycline is able to reduce Wolbachia and prevent the immune response against the bacteria. The combination treatment protocol has been shown to be highly adulticidal and further studies are needed to better understand the interaction between doxycycline and ivermectin in D. immitis infected dogs.

Unusual antibiotic presence in gym trained subjects with food intolerance; a case report.

INTRODUCTION: Great interest is raising in food intolerances due to the lack, in many cases, of a particular sensitizing agent. OBJECTIVE: We investigated the serum level of possible new haptens in 15 heavy meat consumers for sport fitness affected by various kinds of food intolerance and who had ever been administered antibiotics in their life for clinical problems. METHODS: Forty ml of blood were drawn from each patient and analyzed, by means of an ELISA test, in order to possibly identify the presence of an undue contaminant with hapten properties. RESULTS: Four out of fifteen subjects (26%) showed a serum oxytetracycline amount > 6 ng/g (which is considered the safety limit), 10 of 15 (66%) a serum doxycycline amount > of 6 ng/g and 3 out of 15 (30%) subjects had high serum level of both molecules. CONCLUSIONS: Although a direct ratio between body antibiotics remnant storage in the long run and chronic gut dysfunctions and/or food allergy did not reached the evidence yet, the blood traces of these compounds in a food intolerant otherwise healthy population might be considered the preliminary putative step of a sensitizing pathway. Our next goals foresee a deeper insight into the sensitizing trigger from human chronic antibiotic exposure via the zootechnical delivery of poultry food.

Introducción: La falta, en muchos casos, de un agente sensibilizador está despertando un enorme interés en la tolerancia a los alimentos. Objetivo: Investigamos el nivel sérico de posibles nuevos haptenos en 15 grandes consumidores de carne para entrenamiento deportivo afectados por diversos tipos de intolerancia a los alimentos y que habían recibido antibióticos en algún momento de sus vidas por problemas médicos. Métodos: Se realizaron extracciones de sangre de 40ml a cada paciente y se analizaron empleando un test ELISA, para identificar la posible presencia de un elemento contaminante indebido con propiedades de hapteno. Resultados: 4 de 15 sujetos (26%) mostraron una cantidad de oxitetraciclina en suero > 6 ng/g (considerado el límite de seguridad); 10 de 15 (66%) sujetos presentaron una cantidad de doxiciclina > 6 ng/g; y 3 de 15 (30%) sujetos presentaron un alto nivel sérico de ambas moléculas. Conclusiones: Aunque no se llegó a obtener evidencia de una relación directa entre la acumulación de antibióticos corporales a largo plazo y una disfunción intestinal crónica y/o alergias a los alimentos, las trazas en sangre de estos compuestos en una población con alguna intolerancia a los alimentos pero por lo demás sana, podría considerarse el primer paso de una vía de sensibilización. Nuestros próximos objetivos prevén un estudio más profundo del desencadenante sensibilizador a partir de la exposición crónica a antibióticos en humanos por medio de la administración zootécnica de comida avícola.