Doxycycline Therapy Research Articles

Doxycycline decreases proteinuria in glomerulonephritis

Treatment options for crescentic glomerulonephritis include the use of steroids, cytotoxic therapy, and, in severe cases, intravenous immunoglobulins and plasmapheresis. Injury and lysis of capillary glomerular basement membrane, which is made up of type IV collagen, laminin, fibronectin, and proteoglycans, by serine proteinases and matrix metalloproteinases (MMPs) likely is an important participant in the pathogenesis of crescentic glomerulonephritis. Tetracycline derivatives inhibit not only the activity of MMPs, but also their production, and have been investigated for the treatment of disorders in which the MMP system becomes amplified, such as degenerative osteoarthritis, periodontitis, cancer, and abdominal aortic aneurysm. We report an interesting case of crescentic glomerulonephritis in a young man who was treated with cyclophosphamide and prednisone. The patient developed steroid-induced acne that was treated with long-term oral doxycycline therapy. During the period the patient was administered doxycycline, proteinuria decreased by 70% and recurred when doxycycline was stopped. To our knowledge, this is the first report of possible benefits of a metalloproteinase inhibitor (doxycycline) in glomerulonephritis in humans. Future studies are urgently required to explore the option of metalloproteinase inhibitors in the treatment of proliferative glomerulonephritis.

Hautinfektion durch Mycobacterium gordonae bei einem immunkompetenten Patienten

Mycobacterium gordonae ist ein gering pathogenes, in der Umwelt häufig vorkommendes Mykobakterium, das gelegentlich bei immunsupprimierten Patienten, aber nur sehr selten bei Gesunden Hautinfektionen verursacht. Wir berichten über einen 41-jährigen Güterwaggon-Lokführer, der sich ambulant mit seit zwei Jahren bestehenden 7 × 7 cm großen, erythematösen sowie feinlamellär schuppenden Hauläsionen im Bereich des linken Schienbeins vorstellte, die dem klinischen Aspekt eines mikrobiellen Ekzems, eines Granuloma anulare oder einer Necrobiosis lipoidica ähnelten. In der histologischen Untersuchung zeigte sich ein psoriasiformes, lichenoides plasmazelluläres Infiltrat und eine spongiotische Interface-Dermatitis. Die Ziehl-Neelsen-Färbung, die PAS-Reaktion und die Alzianblau-Färbung zum Nachweis von Muzinablagerungen fielen negativ aus. Durch die mikrobiologische Kultur wurde Mycobacterium gordonae nachgewiesen. Die Hautveränderungen waren für eine komplette Exzision zu groß. Es wurde mit einer Kombinationstherapie aus Doxyzyklin und Trimethoprim/Sulfamethoxazol begonnen, jedoch ohne Effekt. Letztlich führte die Therapie mit Clarithromycin (500 mg/d) und Moxifloxacin (400 mg/d) zu einer Regression der Läsionen, so dass eine tuberkulostatische Therapie mit Rifampizin oder Isoniazid nicht für notwendig erachtet wurde.

Esophageal ulceration complicating doxycycline therapy.

To report present state of iatrogenic drug-induced esophageal injury (DIEI) induced by medications in a private clinic. 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). 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. Esophageal ulceration has to be suspected in younger patients with odynophagia, retrosternal burning pain and/or dysphagia during the treatment with doxycycline.

Scrub Typhus: A Frequently Overlooked Cause of Acute Renal Failure

Acute renal failure associated with scrub typhus infection is not rare as previously thought. The possibility of scrub typhus should be borne in mind when patients present with fever and varying degrees of acute renal failure, particularly if an eschar exists, along with a history of environmental exposure in an area like Taiwan, where scrub typhus is endemic. Prompt diagnosis and the use of appropriate antibiotics can rapidly alter the clinical course of the disease and prevent the development of serious or fatal complications. To illustrate the above point, this study reports 3 cases of scrub typhus associated with acute renal failure. They were seen at Chang Gung Memorial Hospital in a 2-year interval. Case 1 was referred from district hospital with clinical features of multiple organ dysfunctions, including shock, fever, acute respiratory failure, acute renal failure, and acute hepatitis. Case 2 was admitted with the chief problems of shock, fever, acute renal failure, and DIC. Case 3 visited our outpatient clinic due to fever, maculopapular rash and acute renal failure. In all these patients, the diagnosis was confirmed using immunofluorescence techniques, which showed that Orientia tsutsugamushi had an IgM titer of 1:80 or greater. Notably, despite having varying degrees of acute renal deterioration, the patients responded very well to doxycycline therapy and recovered completely. Additionally, a total of 4 similar cases of scrub typhus associated with acute renal failure were reviewed from th past literature.

Proinflammatory cytokine profile inVibrio vulnificussepticemic patients’ sera

Vibrio vulnificus causes a fulminant and frequently fatal septicemia in susceptible hosts. The present study was designed to evaluate the proinflammatory cytokine profile in V. vulnificus septicemia patients' sera and the effect of doxycycline therapy on the levels of proinflammatory cytokines. Levels of proinflammatory cytokines, tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta and IL-6, were measured in the sera of V. vulnificus septicemic patients and normal healthy volunteers using colorimetric sandwich ELISA. The mean values of TNF-alpha, IL-1beta and IL-6 in the sera of V. vulnificus patients (n=33) increased by 210-, 232- and 40-fold in comparison with those of normal healthy volunteers (n=5), but only the IL-6 level showed a statistically significant difference (P<0.05) between the two groups. Sera from the cases for which doxycycline treatment histories were obvious were designated 'before-treatment' (TX). All the others were included in the after-TX group. In the before-TX group (n=5), the levels of TNF-alpha and IL-1beta significantly increased (P<0.05) in comparison with the after-TX group (n=5). IL-6 levels in the two groups showed no difference. In conclusion, the levels of the well known proinflammatory cytokines TNF-alpha, IL-1beta and IL-6 increased in the V. vulnificus septicemic patients' sera, and the levels of TNF-alpha and IL-1beta decreased significantly after doxycycline treatment. These data indicate that proinflammatory cytokines might play a critical role in V. vulnificus septicemia like in other endotoxemic shocks. The use of doxycycline as an effective bactericidal agent and as an effective modulator of proinflammatory cytokines is supported.

Proinflammatory cytokine profile in Vibrio vulnificus septicemic patients’ sera

Vibrio vulnificus causes a fulminant and frequently fatal septicemia in susceptible hosts. The present study was designed to evaluate the proinflammatory cytokine profile in V. vulnificus septicemia patients’ sera and the effect of doxycycline therapy on the levels of proinflammatory cytokines. Levels of proinflammatory cytokines, tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6, were measured in the sera of V. vulnificus septicemic patients and normal healthy volunteers using colorimetric sandwich ELISA. The mean values of TNF-α, IL-1β and IL-6 in the sera of V. vulnificus patients ( n=33) increased by 210-, 232- and 40-fold in comparison with those of normal healthy volunteers ( n=5), but only the IL-6 level showed a statistically significant difference ( P<0.05) between the two groups. Sera from the cases for which doxycycline treatment histories were obvious were designated ‘before-treatment’ (TX). All the others were included in the after-TX group. In the before-TX group ( n=5), the levels of TNF-α and IL-1β significantly increased ( P<0.05) in comparison with the after-TX group ( n=5). IL-6 levels in the two groups showed no difference. In conclusion, the levels of the well known proinflammatory cytokines TNF-α, IL-1β and IL-6 increased in the V. vulnificus septicemic patients’ sera, and the levels of TNF-α and IL-1β decreased significantly after doxycycline treatment. These data indicate that proinflammatory cytokines might play a critical role in V. vulnificus septicemia like in other endotoxemic shocks. The use of doxycycline as an effective bactericidal agent and as an effective modulator of proinflammatory cytokines is supported.

A Case of Scrub Typhus with Acute Respiratory Distress Symdrome and Meningoencephalitis

Scrub typhus is an acute, febrile disease of humans that is caused by Orientia Tsutsugamushi. It is transmitted through the bite of chiggers. The spectrum of the clinical severity for scrub typhus ranges from mild to severe with fatal complication such as meningoencephalitis, pneumonitis, myocarditis. Severe pulmonary involvement e.g. acute respiratory distress syndrome(ARDS) and meningoencephalitis have rarely been observed since the introduction of specific antibiotic therapy. We experienced a case of scrub typhus manifested with ARDS and meningoencephalitis. The patient was treated with doxycycline, anticonvulsant and mechanical ventilator therapy.

The effects of intravenous doxycycline therapy for rheumatoid arthritis: A randomized, double‐blind, placebo‐controlled trial

The effects of intravenous doxycycline therapy for rheumatoid arthritis: A randomized, double‐blind, placebo‐controlled trial

Doxycycline and rifampicin for mild scrub-typhus infections in northern Thailand: a randomised trial

Some strains of scrub typhus in northern Thailand are poorly responsive to standard antirickettsial drugs. We therefore did a masked, randomised trial to compare rifampicin with standard doxycycline therapy for patients with scrub typhus. Adult patients with strictly defined, mild scrub typhus were initially randomly assigned 1 week of daily oral treatment with 200 mg doxycycline (n=40), 600 mg rifampicin (n=38), or doxycycline with rifampicin (n=11). During the first year of treatment, the combined regimen was withdrawn because of lack of efficacy and the regimen was replaced with 900 mg rifampicin (n=37). Treatment outcome was assessed by fever clearance time (the time for oral temperature to fall below 37.3 degrees C). About 12,800 fever patients were screened during the 3-year study to recruit 126 patients with confirmed scrub typhus and no other infection, of whom 86 completed therapy. Eight individuals received the combined regimen that was discontinued after 1 year. The median duration of pyrexia was significantly shorter (p=0.01) in the 24 patients treated with 900 mg daily rifampicin (fever clearance time 22.5 h) and in the 26 patients who received 600 mg rifampicin (fever clearance time 27.5 h) than in the 28 patients given doxycycline monotherapy (fever clearance time 52 h). Fever resolved in a significantly higher proportion of patients within 48 h of starting rifampicin (900 mg=79% [19 of 24], 600 mg=77% [20 of 26]) than in patients treated with doxycycline (46% [13 of 28]; p=0.02). Severe gastrointestinal events warranted exclusion of two patients on doxycyline. There were two relapses after doxycycline therapy, but none after rifampicin therapy. Rifampicin is more effective than doxycycline against scrub-typhus infections acquired in northern Thailand, where strains with reduced susceptibility to antibiotics can occur.

Measured versus self-reported compliance with doxycycline therapy for chlamydia-associated syndromes: high therapeutic success rates despite poor compliance.

To compare self-reported doxycycline compliance in men and women attending an STD clinic with indications for Chlamydia trachomatis treatment to compliance measured using microprocessor-containing medication vials to count each time and date medication vials were opened. A secondary objective was to correlate outcomes of therapy, as measured by symptom resolution and persistence of chlamydial nucleic acids, with measured doxycycline compliance. Between September 1995 and July 1997, Medication Event Monitoring System (MEMS) caps were used to measure compliance with recommended doxycycline therapy (14 doses over 7 days) in patients treated for presumed C. trachomatis infections. Polymerase chain reaction (PCR) assays for C. trachomatis were performed on urine specimens collected at the time of follow-up evaluation. Of 221 evaluable participants, although 90% reported taking their medication as directed, only 33 (16%) managed this level of compliance according to data obtained from the MEMS cap. Although 144 (65%) patients took more than 11 of 14 doses over 8 days, 147 (67%) participants had at least one interval of 24 hours or longer between doses in an 8-day period. Of 81 participants with positive C. trachomatis cultures at enrollment, follow-up urine PCR for C. trachomatis was positive in 5 (6%). Medication Event Monitoring System data for four of the five patients with positive PCR tests as follow-up showed each had two or more 24-hour intervals when their medication vials were not opened and three of four had opened their vials less than 11 times. This study suggests that few patients take medications as prescribed and that self-report substantially underestimates medication noncompliance. Despite poor compliance, there were few treatment failures.

Diaphragmatic paralysis due to Lyme disease

Lyme disease is a tick-borne spirochaete infection which, in a proportion of patients, can lead to neuropathy. This article describes a case of diaphragmatic paralysis due to Lyme disease. A 39-yr-old male presented to the hospital because of an acute left facial palsy. Six weeks prior to admission he had developed a circular rash on his left flank during a camping holiday. He also complained of shortness of breath and arthralgia for 1 week. His chest radiograph demonstrated a raised right hemi-diaphragm. Diaphragmatic paralysis was confirmed by fluoroscopy (a positive sniff test). Serology revealed evidence of recent infection by Borrelia burgdorferi. On the basis of the patient's clinical presentation, a recent history of erythema migrans, and positive Lyme serology, a diagnosis of neuroborreliosis was made. He received oral doxycycline therapy (200 mg x day(-1)) for three weeks. Facial and diaphragmatic palsies resolved within eight weeks. On the basis of this case, a diagnosis of Lyme disease should be considered in patients from endemic regions with otherwise unexplained phrenic nerve palsy.

Efficacy of doxycycline and ciprofloxacin against experimental Yersinia pestis infection.

The efficacies of ciprofloxacin and doxycycline prophylaxis and therapy were assessed against experimental pneumonic plague infections induced by two strains of Yersinia pestis in a mouse model. When exposed to an aerosol of Y. pestis strain GB, containing 8.39 x 10(5) +/- 4.17 x 10(4) cfu, the retained dose was 7.3 x 10(3) +/- 2.3 x 10(3) cfu. When exposed to an aerosol of Y. pestis strain CO-92, containing 1.86 x 10(5) +/- 7.4 x 10(3) cfu, the retained dose was 3.4 x 10(4) +/- 2.6 x 10(3) cfu. Both strains resulted in a respiratory and systemic infection closely resembling human pneumonic plague. Ciprofloxacin prophylaxis and therapy was successful against both strains for up to 24 h after challenge, but not after 48 h. Both doxycycline prophylaxis and therapy regimens were ineffective against both strains, although strain CO-92 was more susceptible in vitro to doxycycline than strain GB and supra-MIC levels were achieved in the serum and lungs of the animal.

Compliance with doxycycline therapy in sexually transmitted diseases clinics.

To determine rates of compliance with doxycycline therapy for patients attending two inner city sexually transmitted diseases (STD) clinics using the MEMS (Medication Event Monitoring System) technology (Aprex Corporation, Fremont, CA). An observational study. Two STD clinics in Brooklyn, New York and Birmingham, Alabama. Patients warranting doxycycline as antichlamydial therapy by usual clinical criteria (e.g., documented chlamydial infections, gonococcal urethritis, mucopurulent cervicitis) were enrolled consecutively from both clinics into four separate categories according to gender and the presence or absence of symptoms: symptomatic men (77), asymptomatic men (30), symptomatic women (83), asymptomatic women (33). In the clinic area, patients were given their doxycycline in standard 30-dram medication bottles fitted with the MEMS cap, which is capable of recording the date and time of each bottle opening and closing. This information was then retrieved using a software program developed by the manufacturer. Patients were instructed to return the bottle and cap at the completion of therapy. Efforts were made to contact those who did not return their bottles by both telephone and mail. Bottle openings as recorded by the MEMS were considered to represent use of medication. Patients were considered strictly compliant with prescription instructions if bottle openings and closings occurred at least twice daily for 6 consecutive days. Noncompliance was defined as initially opening the medication more than 48 hours after leaving the clinic or opening the bottle less than once daily for 5 consecutive days. Usage between these extremes was classified as intermediate. Eighty percent of 223 patients enrolled completed the study by returning their bottles. The rate of strict compliance with prescription instruction was 25%. The rate of noncompliance was 24%. Fifty-one percent used some intermediate amount of medication. There was no statistical difference in compliance by gender, presence or absence of symptoms, or site of enrollment. Few patients administered doxycycline in an STD clinic can be expected to take medication precisely as prescribed. Although most probably take enough to eradicate uncomplicated chlamydial infections, a sizable portion can be expected to use an inadequate amount of medication. This may contribute to persistence of genital chlamydia infections in the community.

Doxycycline内服による全周性食道潰瘍の1例

Doxycycline内服による全周性食道潰瘍の1例

Ocular rosacea: signs, symptoms, and tear studies before and after treatment with doxycycline.

Objective: To examine ocular signs, symptoms, and results of tear analysis in patients with cutaneous rosacea before, during, and after doxycycline therapy. Design: Before-after trial. Setting: General community. Patients or Other Participants: Thirty-nine patients with cutaneous rosacea underwent dermatologic and ocular examinations, testing of tear break-up time, and Schirmer testing at baseline and 4, 8, and 12 weeks. Six patients did not complete the study. Baseline tear break-up time and results of Schirmer test were compared with those of 13 patients without rosacea who were matched for age and sex. Intervention: Patients with rosacea were given doxycycline, 100 mg daily for 12 weeks. Main Outcome Measure: Statistically significant (P,.05) improvement in tear break-up time. Result: The most frequent ocular symptoms were dryness, itching, blurred vision, and photosensitivity, all of which improved significantly with treatment. All patients had signs of ocular disease, most commonly erythema and telangiectasia, meibomian gland dysfunction, and ciliary base injection. Significant improvement (P,.05) for scales, erythema and telangiectasia, ciliary base injection, bulbar injection, papillary hypertrophy, and punctate epithelial erosions was seen. Average tear break-up time for the patients with rosacea was 5.7 seconds, which improved to 10.8 seconds after 12 weeks of treatment (P=.007). Baseline tear break-up time was significantly lower than for the comparison group of normal subjects (P=.001). There was no correlation between severity of cutaneous disease and ocular disease. Conclusions: All patients with cutaneous rosacea had some degree of ocular involvement. Tear break-up time is abnormal in patients with rosacea. Ocular erythema and telangiectasia, meibomian gland dysfunction, and short tear break-up time in patients with cutaneous rosacea are indicators of ocular rosacea. Doxycycline, 100 mg daily, will improve ocular disease and increase the tear break-up time. Arch Dermatol. 1997;133:49-54

Ocular Rosacea

<h3>Objective:</h3> To examine ocular signs, symptoms, and results of tear analysis in patients with cutaneous rosacea before, during, and after doxycycline therapy. <h3>Design:</h3> Before-after trial. <h3>Setting:</h3> General community. <h3>Patients or Other Participants:</h3> Thirty-nine patients with cutaneous rosacea underwent dermatologic and ocular examinations, testing of tear break-up time, and Schirmer testing at baseline and 4, 8, and 12 weeks. Six patients did not complete the study. Baseline tear break-up time and results of Schirmer test were compared with those of 13 patients without rosacea who were matched for age and sex. <h3>Intervention:</h3> Patients with rosacea were given doxycycline, 100 mg daily for 12 weeks. <h3>Main Outcome Measure:</h3> Statistically significant (P,.05) improvement in tear break-up time. <h3>Result:</h3> The most frequent ocular symptoms were dryness, itching, blurred vision, and photosensitivity, all of which improved significantly with treatment. All patients had signs of ocular disease, most commonly erythema and telangiectasia, meibomian gland dysfunction, and ciliary base injection. Significant improvement (P,.05) for scales, erythema and telangiectasia, ciliary base injection, bulbar injection, papillary hypertrophy, and punctate epithelial erosions was seen. Average tear break-up time for the patients with rosacea was 5.7 seconds, which improved to 10.8 seconds after 12 weeks of treatment (<i>P</i>=.007). Baseline tear break-up time was significantly lower than for the comparison group of normal subjects (<i>P</i>=.001). There was no correlation between severity of cutaneous disease and ocular disease. <h3>Conclusions:</h3> All patients with cutaneous rosacea had some degree of ocular involvement. Tear break-up time is abnormal in patients with rosacea. Ocular erythema and telangiectasia, meibomian gland dysfunction, and short tear break-up time in patients with cutaneous rosacea are indicators of ocular rosacea. Doxycycline, 100 mg daily, will improve ocular disease and increase the tear break-up time. Arch Dermatol. 1997;133:49-54

Cost Effectiveness Analysis of Azithromycin and Doxycycline forChlamydia TrachomatisInfection in Women: A Canadian Perspective

To assess the cost effectiveness of azithromycin versus doxycycline therapy for cervical Chlamydia trachomatis infections in Canada. A predictive decision analytic model using previously published clinical and economic evaluations, expert opinion and costs of medical care in Canada. A hypothetical cohort of 5000 women followed over 10 years. Two diagnostic strategies were compared, laboratory confirmed diagnosis (LCD) and presumptive diagnosis (PD) of C trachomatis infection. Under each strategy, two treatment alternatives were analyzed, a single 1 g dose of azithromycin and a seven-day course of doxycycline as 100 mg twice daily. Despite a fourfold higher acquisition cost, under base case conditions, for both diagnostic strategies, the azithromycin treatment alternative was more cost effective than the doxycycline alternative. For the LCD model, the cost per cure for patients receiving azithromycin was $184.76 compared with $240.59 for patients receiving doxycycline, resulting in an incremental cost of $55.83. For the PD model, the cost per cure for patients treated with azithromycin was $51.48 compared with $51.82, resulting in an incremental cost of $0.34. For the hypothetical cohort of 5000 women, the use of azithromycin translates into a projected annual cost savings of $279,150 and $1,700 for the LCD and PD models, respectively. In one-way sensitivity analyses for the LCD model, no clinically plausible changes in the base case estimates changed the results of the cost effectiveness outcome. In the PD model, clinically plausible changes in the probabilities of doxycycline cure, pelvic inflammatory disease, sequelae and chlamydia infection were found to alter the cost effectiveness outcome. Based on the results from our model, the azithromycin strategy should be employed for the treatment of laboratory confirmed cases. However, for presumptive cases, azithromycin should be used only if the probabilities of C trachomatis and pelvic inflammatory disease are more than 19%, doxycycline effectiveness is less than 78%, or the cost of azithromycin is less than $19.00.

Doxycycline or ciprofloxacin prophylaxis and therapy against experimental Yersinia pestis infection in mice.

The efficacy of doxycycline and ciprofloxacin against an experimental plague infection was assessed by comparing the median lethal dose (MLD) of Yersinia pestis in antibiotic-treated and untreated mice. The MLD of Y. pestis GB strain in untreated mice by the intra-peritoneal route was 23 cfu. If ciprofloxacin dosage (20 or 40 mg/kg twice daily) was initiated 48 h before infection, it afforded complete protection against an intra-peritoneal challenge of 5.24 x 10(7) cfu. Ciprofloxacin therapy initiated 24 h post-challenge was less protective, the MLD was raised to 2.0 x 10(5) and 2.2 x 10(5) cfu for 40 and 20 mg/kg respectively. Doxycycline dosage (40 mg/kg twice daily) initiated 48 h prior to infection raised the MLD to 1.6 x 10(4) cfu, but other prophylactic and therapeutic regimes were ineffective against challenges greater than 6.76 x 10(2) cfu. Ciprofloxacin may therefore be a useful antibiotic to consider for the treatment of plague.

Azithromycin in the management of Chlamydia trachomatis infections.

The unique pharmacological profile of the azalide macrolide azithromycin, coupled with its in vitro activity against both Chlamydia trachomatis and the ureaplasmas, suggested that genital infections caused by these bacteria could be successfully treated with a single dose of the antibiotic. This has now been confirmed in worldwide clinical studies. A single oral dose of azithromycin 1 g eradicates C. trachomatis in almost 100% of cases of non-gonococcal urethritis and cervicitis. Unfortunately, there are no specific clinical signs for genital chlamydial infection. It is therefore necessary to use therapy effective against known and unknown pathogens for treating lower genital tract infection. Clinical cure rates for both chlamydial and non-chlamydial, non-gonococcal infections compare favourably with standard 7-day doxycycline therapy, being in excess of 85%. Side effects are few (< 20%) and essentially minor.

Enteric Coating Reduces Upper Gastrointestinal Adverse Reactions to Doxycycline.

A new doxycycline formulation consisting of enteric-coated doxycycline hyclate pellets in capsules is aimed at reducing gastrointestinal adverse reactions related to doxycycline therapy. In this randomised, double-blind, 3-way crossover study, adverse reactions caused by short term treatment with enteric-coated doxycycline hyclate pellets in capsules were compared with placebo and doxycycline monohydrate tablets. The latter are generally considered to be better tolerated than older formulations of doxycycline hyclate. 111 healthy volunteers completed the study. They were given 150mg of doxycycline once daily over 3 consecutive days with a washout of 4 to 10 days between the study periods. The medication was administered after an overnight fast (10 hours) with 200ml of tap water. An upright position was maintained for 1 hour and no food was allowed for 2 hours after drug administration. Participants recorded adverse reactions daily. Adverse reactions were reported by 66% of the subjects during treatment with doxycycline monohydrate, while 43% reported adverse reactions during treatment with enteric-coated doxycycline hyclate and 30% during placebo. Compared with the 2 other groups, doxycycline monohydrate caused significantly more adverse reactions in general, and abdominal pain, nausea and vomiting in particular. It is concluded that enteric-coated doxycycline hyclate pellets in capsules have significantly better gastrointestinal tolerability compared with doxycycline monohydrate.