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Mepartricin is a semi-synthetic macrolide antibiotic developed as a drug for the treatment of benign prostatic hyperplasia (BPH) in human patients. In the present study, aged rats are used as an experimental model to evaluate the effects of mepartricin on circulating hormone concentrations and prostate receptor concentrations, to compare these possible effects with clinical findings observed in long-term treated dogs. Fifty-six aged male rats were randomly divided into four experimental groups treated orally with 0 (group 1), 2 mg (group 2), 5 mg (group 3) and 20 mg (group 4) mepartricin/kg of body weight. for 28 days respectively. Serum oestradiol and testosterone concentrations were measured by radio-immune-assays methods. Binding assays were used to measure the prostate concentrations of oestrogen receptors (ER), androgen receptors (AnR), alpha(1)-adrenergic receptor (alpha(1)-AR), and beta-adrenerergic receptor (beta-AR) subtypes. Mepartricin induced a significant reduction of prostate weight and serum oestradiol concentrations. Serum testosterone concentrations were unaffected. The treatment induced a significant down-regulation of ER concentrations (P < 0.05) and a significant up-regulation of AnR (P < 0.05) in rat prostate. Mepartricin induced a significant (P < 0.05) dose-dependent up-regulation of alpha(1)-AR and beta(2)-AR. In contrast, the concentration of beta(3)-ARs was significantly decreased (P < 0.05) in treated animals. The increase in prostate beta(2)-AR concentrations observed in subjects treated with mepartricin may be a favourable element in the evolution of BPH, because of the role exerted by these receptors in the control of prostatic smooth muscle relaxation. Curiously, beta(3)-AR concentrations were significantly reduced in treated animals. Data collected suggest that the prostatic beta-AR expression might be strongly influenced by oestrogen deprivation (mepartricin treatment); therefore, the combination of oestrogen suppression (mepartricin) and adrenergic suppression (alpha(1)-AR blockers) may be proposed as a possible nonhormonal therapeutic strategy for the treatment of benign prostatic hyperplasia in dogs.

Objective: The effects of mepartricin (S-160) on spontaneous canine benign prostatic hyperplasia (BPH) were investigated by histological, histochemical and biochemical analysis., Methods: Aged beagle dogs (5-9 years old) with spontaneously developed BPH were treated orally with a placebo or S-160 (5, 10 or 20 mg/kg/day) for 8 weeks. The methodology included measurement of prostatic volume by transrectal ultrasonography, qualitative evaluation of prostatic morphology, determination of plasma and intraprostatic estradiol level by radioimmunoassay and immunohistochemical detection of estrogen receptors and androgen receptors in the prostate., Results: S-160 significantly reduced the prostatic volume and regressed histologically the hyperplastic grade of prostate, and also fairly decreased the plasma and intraprostatic estradiol concentration and the estrogen and androgen receptors in the prostate., Conclusions: These results suggest that the reduction of estradiol and estrogen receptors in the prostate may play a crucial role in the regression of BPH by S-160.

The therapeutic efficacy and tolerance of a new 150,000 U (40 mg) formulation of mepartricin (to be administered once-a-day in the evening) were evaluated during a double-blind study against placebo in 2 groups of uncomplicated BPH patients treated for 60 days. The data obtained disclosed a positive pharmaco-therapeutic effect of this new formulation coupled with excellent local and systemic tolerance. At the end of trial the various objective and subjective parameters considered showed marked improvement in the group treated with mepartricin, with statistically significant differences from the placebo-treated group. The treatment efficacy was judged positive in 74-78% of cases by patients and physicians in the mepartricin group and in 36.4% of cases in the placebo group.

A group of 25 patients with uncomplicated BPH was treated mepartricin 150,000 U (40 mg) once in the evening for 60 days and the results were compared with those obtained in 25 patients treated with mepartricin 50,000 U (13 mg) t.d.s. Efficacy and tolerance of both treatment schemes were good. In the group treated with on single dose at night some symptoms such as nocturia and pollakiuria regressed more rapidly.

The effects of partricin methyl ester, administered to 481 BPH patients at the dose of 150.000 U as a single administration at night for 90 days were studied in the course of a multicentre study. The favourable evolution of the objective and subjective symptomatologic parameters taken into consideration confirmed the efficacy of the substance used even by this mode of administration. The size of the patient sample ensured that reliable findings were obtained as regards the excellent safety of this form of dosage.

Treatment of both male and female rats with 5 IU/day mepartricin for 7-10 days administered by gastric tubing resulted in an increased faecal excretion of some steroids. Mean rate of elimination of total oestrogens was enhanced by 45% in male rats and by 14% in female rats, and the average excretion of conjugated oestrogen was also increased in the female animals. Faecal elimination of cholesterol was 37% and 42% higher in male and female rats, respectively, after mepartricin treatment, and in male rats plasma concentrations of cholesterol were reduced following treatment. It is suggested mepartricin acts either by changing the intestinal flora or by acting directly on the steroid moieties, and it is speculated that a similar mechanism may occur in man.

In order to more throughly study mepartricin pharmacodynamic characteristics, 2 groups of 15 patients with BPH and coexistent lipid metabolism disorders were studied in conformity with a sequential experimental design during which also systemic-acting (procetofen) and endoluminal-acting (cholestyramine) fat-lowering drugs were tried. The data obtained confirmed mepartricin specific effect on symptomatology and function in BPH and demonstrated the absence of positive and/or negative pharmacological interactions between the substance in question and the fat-lowering agents tried.

Mepartricin, a new semisynthetic heptene, was given for systemic Candida infections to 11 immunocompromised patients. All patients were undergoing bone marrow transplantation or treatment with antilymphocytic globulin: 6 had acute leukemia, 4 aplastic anemia and 1 had Wiskott-Aldrich syndrome. In all patients systemic Candida infection was diagnosed on the basis of fungemia or positive cultures from at least three different sites, two of which were outside the gut. Mepartricin was given intravenously as a slow drip, at the dose of 100-700 U/kg/day for a total of 198 patient-days (range 9-36, mean +/- SD 18 +/- 8). Patients had to be premedicated with steroids and antihistamines to avoid reactions such as chills and fever. The treatment was well tolerated in all patients, and renal function tests were unchanged during therapy. There was a complete resolution of the fungal infection in 10 of the 11 patients.

Acute toxicity and absorption data of a soluble complex of mepartricin with sodium laurylsulphate (SPA-S-222) active against C. albicans and T. vaginalis are reported. The results demonstrate an improved bioavailability with respect to the insoluble substance. Preliminary clinical trials proved the good tolerance of the substance and its effectiveness in oral treatment of vaginal trichomoniasis.

44 patients with candidal vaginitis participated in a trial using a new formulation of a mepartricin-sodium lauryl sulfate complex for local administration (dosage schedule: one 25,000-unit vaginal tablet (SPA-S-222) daily for 6 days). Microbiological examination revealed an 88.6% cure rate (samples tested negative) at the end of treatment and a 90.9% cure rate 30 days after cessation of treatment. In addition, the clinical symptoms observed at the beginning of treatment disappeared rapidly and the patients showed great clinical improvement under the present therapy. Both local and systemic tolerance of the preparation used were excellent.

Mepartricin, the methyl ester of partricin, is a new polyene antibiotic with antifungal and antiprotozoal activity. The antitrichomonas activity in vitro is comparable to that of metronidazole, the widely used drug recently demonstrated to possess mutagenic activity and thus to be used with caution in therapy. Clinical investigations have shown that mepartricin can be successfully used in the topic treatment of vaginal trichomoniasis and candidiasis. The mutagenic activity of mepartricin has been evaluated using the Ames' test and compared to that of metronidazole. No mutagenic activity was detected for mepartricin. The drug can thus be proposed as a safer and efficient alternative to metronidazole.

Fifteen patients in various stages of benign hypertrophy of the prostate were treated with mepartricin (SPA-S-160). Three tablets a day were given for a standard period of 60 days. The pharmacological effect of the drug was assessed both by traditional techniques and modern instrumental examinations like transrectal echography and urodynamic analysis. All 15 patients were studied on the basis of a protocol that incorporated standard diagnostic surveys before the start of treatment, numerous tests after 30 days and at the end of treatment. The overall clinical result was more than satisfactory especially in terms of the reduction in the frequency of daily and nightly urination. The echographic and urodynamic results were less spectacular. The drug was extremely well tolerated.

The effect of a new polyene antibiotic prepared in an oral suspension (SPA methyl-partricin) was studied in 29 nurselings with thrush. The results are compared with those obtained in two uniform groups treated with nystatin and gentian violet respectively. The new substance proved more effective in each case. Local and general tolerance were excellent.

A "cross over" study was carried out in a group of 22 subjects with prostatic hypertrophy in different stages, first treated with chloroformic extract of Pygeum Africanum (4 capsules/die for 30 days) and afterwards, when the symptoms reappeared, with mepartricin (3 gastroresistant tablets of 50,000 U. each/die for 30 days). Both substances proved to be active against the urinary symptomatology; however the polyene induced a significant decrease in the prostate size (evaluated by cystography), justifying the 77% of "excellent" results against the 13% obtained with the reference drug.

The efficacy and tolerance of mepartricin sodium lauryl sulphate (SPA-S-222) was evaluated in patients with vaginal trichomoniasis and/or moniliasis. One group received 4 tablets/day for 3 days (group "A"), and the other (group "B") 1 tablet/8 hr for 4 days. A lasting microbiological cure was obtained in all cases. Tolerance was better in group "B" and it is felt that this protocol should be preferred.