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Is combined oral and topical therapy better than oral therapy alone in patients with moderate to moderately severe acne vulgaris? A comparison of the efficacy and safety of lymecycline plus adapalene gel 0.1%, versus lymecycline plus gel vehicle.

This multicenter, randomized, investigator-blinded study compared the efficacy and tolerability of a combination of lymecycline 300 mg/day orally and adapalene topical gel 0.1% (n = 118) to lymecycline 300 mg/day orally plus vehicle gel (n = 124) in patients with moderate to moderately severe acne vulgaris with both inflammatory and noninflammatory lesions. The primary efficacy end point, total lesion count at end point (last observation carried forward), showed a statistically significant difference in favor of the lymecycline plus adapalene group (P =.0011). The mean decrease in total, inflammatory and noninflammatory lesion counts was significantly greater at end point in the lymecycline plus adapalene group than in the lymecycline plus vehicle group (P <.01). In addition, a significant difference for inflammatory and total acne lesions was seen sooner in the adapalene plus lymecycline group. In total, 75.5% of patients in the lymecycline plus adapalene group were markedly improved, almost clear or clear of their lesions at week 12, compared with 51.8% of those in the lymecycline plus vehicle group (P <.001). Local cutaneous tolerance was generally good in both groups, although more patients receiving the lymecycline plus adapalene combination experienced cutaneous reactions than those receiving lymecycline plus vehicle. There are relatively few studies comparing the efficacy of combined oral and topical therapy with either individual therapy alone. This study clearly demonstrates that lymecycline plus adapalene combination treatment resulted in a significantly greater mean decrease in the number of inflammatory, noninflammatory and total lesions than lymecycline plus vehicle and was well tolerated.

Acne Vulgaris↗

The use of lymecycline in the treatment of moderate to severe acne vulgaris: a comparison of the efficacy and safety of two dosing regimens.

We compared the efficacy and safety of lymecycline 300 mg od vs lymecycline 150 mg bid or placebo in the treatment of moderate to severe acne. 271 patients received either oral lymecycline 300 mg od + placebo od, lymecycline 150 mg bid, or placebo bid, for 12 weeks. Reduction in inflammatory lesion counts at week 12 was the primary efficacy variable (global improvement was a primary efficacy parameter vs placebo) and safety was assessed by adverse events. Lymecycline 300 mg od was non-inferior to lymecycline 150 mg bid at all time points and superior to placebo throughout the study. Drug-related adverse events were similar for all treatment groups. Lymecycline 300 mg od is as effective and safe as lymecycline 150 mg bid in the treatment of moderate to severe acne. This new, once daily formulation could potentially contribute towards improved compliance rates with oral tetracyclines.

Acne Vulgaris↗

A comparison of the efficacy and safety of lymecycline and minocycline in patients with moderately severe acne vulgaris.

A multicentre, randomised, double-blind and double-dummy study was conducted to compare the efficacy and safety of lymecycline (n = 71) with that of minocycline (n = 73) in 144 patients with moderately severe acne vulgaris. Patients with an acne score of 1-5 on the Leeds scale received oral lymecycline, 300 mg/day for 2 weeks, then 150 mg/day for 10 weeks or oral minocycline, 100 mg/day for 2 weeks then 100 mg every other day for 10 weeks. Inflammatory, non-inflammatory and total lesion counts were determined at baseline (week 0) and after 4, 8 and 12 weeks' treatment, and global efficacy and safety assessments were made by the patient and investigator at the end of the study. Both treatments were equally effective at reducing differential lesion counts and improving acne condition and severity, with no significant differences between treatments. Inflammatory lesions were reduced by 50.6% and 52.2% with lymecycline and minocycline, respectively, and non-inflammatory lesions by 40.6% and 32.2%. Acne severity was reduced by 42.4% with lymecycline and by 47.9% with minocycline. A total of 4.3% of lymecycline recipients and 4.1% of minocycline recipients experienced treatment-related adverse events, the majority of which were mild in nature. Lymecycline was as effective as minocycline for the treatment of moderately severe acne vulgaris. Both treatments were well tolerated, although there were slightly fewer adverse gastrointestinal and dermatological effects with lymecycline.

Acne Vulgaris↗

Pharmacokinetics of lymecycline and doxycycline in serum and suction blister fluid.

In an open, random, cross-over trial, 8 young healthy volunteers were given standard doses of lymecycline and doxycycline for 2 days to achieve steady state. The pharmacokinetics of each tetracycline in serum and dermal, suction blister fluid were determined after oral doses of 300 mg lymecycline or 100 mg doxycycline on the 3rd day. Serum concentrations were higher for lymecycline than for doxycycline, the difference being statistically significant from 3 to 9 h after dosing. Also blister concentrations were higher for lymecycline than for doxycycline, though the difference was not statistically significant. The serum half-life for lymecycline was close to 10 h, for doxycycline 12 h. According to our results, both lymecycline and doxycycline should be regarded as 'intermediate-acting' tetracyclines, and each should consequently be dosed twice daily.

Adult↗

Lymecycline in the treatment of acne: an efficacious, safe and cost-effective alternative to minocycline.

A comparison of efficacy, safety and cost-effectiveness of lymecycline and minocycline in the treatment of acne vulgaris has been addressed. This was a multicenter, randomized, investigator-masked, parallel group trial involving patients with moderate to moderately severe acne vulgaris, receiving either lymecycline or minocycline for 12 weeks. Efficacy and safety evaluation was performed at baseline and at weeks 4, 8, and 12 and completed by a pharmacoeconomic analysis including week 12 data. One hundred and thirty-six patients were enrolled. At week 12, the mean percent reductions in inflammatory count were 63 % and 65 %, and for total lesions counts 58 % and 56 % for lymecycline and for minocycline respectively. Median percent reduction in non-inflammatory count were 54 % and 47 % for lymecycline and for minocycline respectively. Eighty-seven per cent of all patients tolerated the treatments well. Treatment with lymecycline was found to be 4 times more cost-effective than with minocycline. Results showed that lymecycline has a comparable efficacy and safety profile to minocycline while being 4 times more cost-effective.

Acne Vulgaris↗

Treatment of infection due to penicillinase-producing Neisseria gonorrhoeae with oral thiamphenicol and with oral lymecycline.

Seventy-five men with gonococcal urethritis were treated with a single oral dose of thiamphenicol, and 88 men with this infection were treated with two 1.5-g oral doses of lymecycline taken 12 hr apart. Of the 75 subjects treated with thiamphenicol, 72 (96%) were cured, as compared with 80 (91%) treated with lymecycline. Sixty subjects (37%) were infected with penicillinase-producing Neisseria gonorrhoeae. In this group, 28 (97%) of 29 subjects treated with thiamphenicol were cured, as compared with 29 (94%) of 31 subjects treated with lymecycline. Patient compliance with the two-dose regimen was excellent, and no adverse effects occurred with either drug. Lymecycline may therefore be an effective alternative to thiamphenicol in those countries where strains of N. gonorrhoeae remain sensitive to the tetracyclines.

Clinical Trials as Topic↗

A single-blind comparative clinical trial of lymecycline and amoxycillin in the treatment of acute bronchitis in general practice.

A single-blind comparison of lymecycline and amoxycillin was performed by three general practitioners in the treatment of acute bronchitis. A total of 132 patients were treated for seven days with lymecycline (204 mg) two capsules twice daily or amoxycillin 250 mg three times daily. Symptoms and signs assessed were cough, dyspnoea, sputum volume, purulence of sputum and temperature. Both drugs brought about a statistically significant improvement. For all parameters the improvements seen with lymecycline were superior to those seen with amoxycillin although in no case did any of these reach statistical significance. However, in the case of purulent sputum those patients receiving lymecycline showed improvement which reached borderline significance (0-05 less than p less than 0-1) as compared with amoxycillin. Side-effects in the case of both drugs were negligible.

Acute Disease↗

The anticollagenolytic potential of lymecycline in the long-term treatment of reactive arthritis.

OBJECTIVE: We sought to determine the antiinflammatory properties of lymecycline in the long-term treatment of reactive arthritis (ReA). METHODS: Quantitative assay of collagenase activity by densitometry after sodium dodecyl sulfate-polyacrylamide gel electrophoresis. RESULTS: Therapeutic levels of lymecycline do not directly inhibit the activity of human neutrophil interstitial collagenase, but can prevent the oxidative activation of latent human neutrophil collagenase. CONCLUSION: This non-antimicrobial, anticollagenolytic property of lymecycline may contribute to its therapeutic efficacy in the treatment of patients with ReA.

Arthritis, Reactive↗

Preventive lymecycline therapy in women with a history of pelvic inflammatory disease undergoing first-trimester abortion: a clinical, controlled trial.

In a clinical, controlled trial 55 women with a history of pelvic inflammatory disease (PID) undergoing first-trimester abortion were randomized to either lymecycline therapy or placebo. Twenty-four women received lymecycline capsules 300 mg b.i.d. for 14 days starting on the morning of the abortion and 31 received similar placebo medication. In the lymecycline group 2 women (8.3%) and in the placebo group 7 (22.6%) contracted postabortal PID, a non-significant difference (p greater than 0.2). The variables age, gestational age, number of spontaneous abortions, births and episodes of PID, and Hegar size were not associated with the rate of postabortal PID. Women without previous induced abortions had a significantly increased rate of postabortal infection (p = 0.02), but the treatment did not influence this rate. Three women had a positive culture for Chlamydia trachomatis at the time of abortion and two of these had postabortal PID. None of 7 women with postabortal PID had significant increases in IgA, IgG or IgM chlamydia antibody titers, but two women with uncomplicated abortions had serological evidence of infection. The number of hospital days and amounts of antibiotics prescribed to women with postabortal PID were not significantly different between the two treatment groups (p greater than 0.05). Women with a history of PID had an elevated risk of postabortal PID warranting the use of some sort of prophylaxis, and screening for C. trachomatis in an abortion population is recommended.

Abortion, Induced↗

Comparative bioavailability of tetracycline and lymecycline.

The relative bioavailability of lymecycline and tetracycline hydrochloride was compared in 12 healthy volunteers in a double-blind cross-over study using a high performance liquid chromatographic method for plasma and urine analyses. A statistical significant difference in favour of tetracycline hydrochloride was found concerning the mean AUC and the mean lag time. The relative bioavailability of lymecycline was only 70% compared with tetracycline in multiple dosing (19.13 +/- 5.39 micrograms ml-1 h and 27.22 +/- 6.26 micrograms ml-1 h respectively) and 80% in a single dose (21.88 +/- 4.23 micrograms ml-1 h and 26.91 +/- 6.01 respectively) and the mean lag time of tetracycline was only 60% compared with lymecycline.

Adult↗

Differences in phototoxic potency should be considered when tetracyclines are prescribed during summer-time. A study on doxycycline and lymecycline in human volunteers, using an objective method for recording erythema.

In order to test the phototoxic potency of the two tetracyclines most frequently prescribed in Sweden, a double-blind cross-over study using a double-dummy technique with doxycycline 0.1 g twice daily, lymecycline 0.6 g twice daily, and placebo, was performed in 15 healthy volunteers. Drugs were given for 3 consecutive days, and on the third day volunteers were tested with 25, 50, 75 and 100 J/cm2 of artificial long-wave ultraviolet radiation (UVA), and assessed 6 h later for erythematous photoreactions. Objective readings were made using skin reflectance spectrophotometry. All three substances were tested in each individual at weekly intervals. Within 50, 75 and 100 J/cm2 of UVA, lymecycline showed a slight increase in erythema compared with placebo, but this was not significant (50 and 100 J/cm2), or was of low significance (75 J/cm2). However, with the same doses, doxycycline showed a substantial increase in erythema compared with placebo, which was highly significant. We conclude that doxycycline has a higher phototoxic potency than lymecycline, and this is in agreement with earlier in vitro experimental data. We recommend that therapy with doxycycline is avoided during summer-time, and during holidays in a sunny climate.

Adult↗

Lymecycline and minocycline in inflammatory acne: a randomized, double-blind intent-to-treat study on clinical and in vivo antibacterial efficacy.

BACKGROUND: Some antibiotics represent a mainstay in acne treatment. However, studies comparing their efficacies are rare. AIM: To evaluate the clinical and in vivo antibacterial effect of lymecycline and minocycline at different dosages. METHOD: Eighty-six patients with moderate to severe acne were enrolled in a randomized, double-blind, intent-to-treat study comparing in three parallel groups the effect of (1) lymecycline 300 mg daily for 12 weeks, (2) minocycline 50 mg daily for 12 weeks and (3) minocycline 100 mg daily for 4 weeks followed by 50 mg daily for 8 weeks. Evaluations were made at the screening visit and at five on-treatment visits. They consisted of clinical counts of acne lesions and evaluations of bacterial viability using dual flow cytometry performed on microorganisms collected from sebaceous infundibula by cyanoacrylate strippings. RESULTS: Patients receiving minocycline 100/50 mg had the best clinical outcome, particularly in the reduction of the number of papules. By the end of the trial, the microbial response to minocycline 100/ 50 mg was also superior to either of the other two treatments. There were less live and more dead bacteria. CONCLUSION: In this trial, minocycline 100/50 mg was superior for the treatment of inflammatory acne when compared to lymecycline 300 mg and minocycline 50 mg.

Acne Vulgaris↗

Penetration of lymecycline (tetracycline) into the tissues of the Fallopian tube.

On the basis of a comparison of different methods used to determine the concentration of active lymecycline in Fallopian tube tissue, a method was adopted which allowed the determination of lymecycline in serosa and mucosa tissue of the Fallopian tube in 16 women undergoing hysterectomy. A difference in the concentration of active drug was found in serosa (greater than 1.7 mg/kg tissue) and mucosa (greater than 0.8 mg/kg tissue) in 16 patients on lymecycline therapy for 24 hours. These figures were fairly constant for the 7.5 hours following the administration. The figures are discussed in relation to the MIC values of the commonly found microorganisms in salpingitis.

Adult↗

Double-blind, placebo-controlled study of three-month treatment with lymecycline in reactive arthritis, with special reference to Chlamydia arthritis.

We conducted a double-blind, placebo-controlled, randomized study of 3-month treatment with lymecycline, a form of tetracycline, in reactive arthritis (ReA). Lymecycline therapy significantly decreased the duration of the illness in patients with Chlamydia trachomatis-triggered ReA, but not in other ReA patients. In 2 ReA patients, C trachomatis was found in the throat, an uncommon locale for this organism. Our results suggest that it is important to verify the triggering microbe and that it is beneficial to treat Chlamydia arthritis patients with a prolonged course of tetracycline.

Adult↗

Distribution of lymecycline in interstitial fluid and paranasal sinus mucosa. An experimental and clinical study.

A comparison between different methods of determining the levels of lymecycline in tissue is presented. The drug levels have been compared with those registered, during the steady state condition, in interstitial fluid obtained from subcutaneously implated tissue cages in rabbits. The 'tissue piece diffusion method' developed is reproducible; it allows antibiotic levels to be determined in minute pieces of tissues, and it seems to measure the total diffusable drug in the interstitial fluid phase. This method was employed in the analyses of lymecycline concentrations in the maxillary sinus mucosa in 12 patients, and it demonstrated a good penetration into the tissue. The level reached was well above the Minimal Inhibitory Concentration of most bacteria causing maxillary sinusitis.

Animals↗

Prophylaxis with lymecycline in induced first-trimester abortion: a clinical, controlled trial assessing the role of Chlamydia trachomatis and Mycoplasma hominis.

A clinical, controlled trial was performed to study the effect of prophylaxis with lymecycline and the role of Chlamydia trachomatis and Mycoplasma hominis in postabortal genital infection. Of 532 women who were to undergo first-trimester abortion, 269 were randomized to treatment with oral lymecycline (300 mg bid) starting 2 days before the abortion and continuing for a total of 7 days, and 263 were randomized to placebo treatment. The rate of postabortal infection was 9.3% in the antibiotic group and 9.5% in the placebo group, an insignificant difference (P greater than .8). The presence of C. trachomatis in the cervix/urethra at the time of abortion showed a significant association with the occurrence of postabortal infection (P less than .005), but there was no correlation between the effect of treatment and the presence of infection (P greater than .4). The presence of M. hominis, a history of pelvic inflammatory disease, maternal age, gestational age, the number of births, spontaneous and induced abortion, and the Hegar number showed no significant association with postabortal infection (all P values greater than .05). It is recommended that women who are to undergo induced abortion be examined for the presence of C. trachomatis and treated, as they constitute a risk group.

Abortion, Induced↗

Lymecycline and concurrent ingestion of milk.

It has been suggested in the past that milk causes an impaired absorption of tetracycline and this paper describes a study set up to examine any inhibition of absorption of a tetracycline derivative, lymecycline (Tetralysal) with the concurrent intake of milk. The results of the study show no clinical reason for restricting a moderate intake of milk in conjunction with lymecycline therapy.

Animals↗

Antibiotic treatment of acute salpingitis. A study of plasma concentrations of two tetracyclines (doxycycline and lymecycline).

A group of 782 patients with a diagnosis of acute salpingitis (a few of the patients because of other infection in the pelvis) were treated with the recommended oral dose of doxycycline (200 mg the first day and 100 mg once daily for at least the following 9-12 days) in combination with 1 g benzyl penicillin and 0.6 g procaine penicillin twice daily intramuscularly for 5-7 days. The plasma concentrations of doxycycline were determined on the third day of treatment before the next dose was given. In 26.5% of the patients the concentrations were below 1 microgram/ml plasma, considered as the minimum therapeutic level. The dose of doxycycline was increased to 200 mg a day in these patients and the plasma concentrations increased accordingly. In another group of 80 patients, 40 were treated with the standard doxycycline dose, and the other 40 patients with the standard lymecycline dose (300 mg twice a day). The plasma concentrations, determined before the dose on the third day, were below 1 microgram/ml in 35% of the patients treated with doxycycline, and in 5% of those treated with lymecycline. Since acute salpingitis in most cases is a serious complication to a lower genital tract infection, often a sexually transmitted disease caused by tetracycline-sensitive organisms, the importance of achieving and determining the therapeutic plasma concentrations of tetracyclines is stressed.

Acute Disease↗