BACKGROUND: Randomized controlled studies of combination therapies in rosacea are limited. OBJECTIVE: Evaluate the efficacy and safety of combining ivermectin 1% cream (IVM) and doxycycline 40-mg modified-release capsules (ie, 30-mg immediate-release and 10-mg delayed-release beads) (DMR) versus IVM and placebo for treatment of severe rosacea. METHODS: This 12-week, multicenter, randomized, investigator-blinded, parallel-group comparative study randomized adult subjects with severe rosacea (Investigator's Global Assessment [IGA] score, 4) to receive either IVM and DMR (combination arm) or IVM and placebo (monotherapy). RESULTS: A total of 273 subjects participated. IVM and DMR displayed superior efficacy in reduction of inflammatory lesions (-80.3% vs -73.6% for monotherapy [P = .032]) and IGA score (P = .032). Combination therapy had a faster onset of action as of week 4; it significantly increased the number of subjects achieving an IGA score of 0 (11.9% vs 5.1% [P = .043]) and 100% lesion reduction (17.8% vs 7.2% [P = .006]) at week 12. Both treatments reduced the Clinician's Erythema Assessment score, stinging/burning, flushing episodes, Dermatology Life Quality Index score, and ocular signs/symptoms and were well tolerated. LIMITATIONS: The duration of the study prevented evaluation of potential recurrences or further improvements. CONCLUSION: Combining IVM and DMR can produce faster responses, improve response rates, and increase patient satisfaction in cases of severe rosacea.

• Klíčová slova
• clear, combination therapy, concomitant use, doxycycline, individualized treatment, ivermectin, rosacea, rosacea treatment, severe rosacea,
• MeSH
• aplikace orální MeSH
• časové faktory MeSH
• dospělí MeSH
• doxycyklin aplikace a dávkování   MeSH
• ivermektin aplikace a dávkování   MeSH
• kombinovaná farmakoterapie metody   MeSH
• kvalita života MeSH
• léky s prodlouženým účinkem aplikace a dávkování   MeSH
• lidé MeSH
• placeba aplikace a dávkování   MeSH
• pleťový krém aplikace a dávkování   MeSH
• rosacea komplikace   diagnóza   farmakoterapie   MeSH
• spokojenost pacientů MeSH
• stupeň závažnosti nemoci MeSH
• tobolky MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze III MeSH
• klinické zkoušky, fáze IV MeSH
• multicentrická studie MeSH
• randomizované kontrolované studie MeSH
• srovnávací studie MeSH
• Názvy látek
• doxycyklin MeSH
• ivermektin MeSH
• léky s prodlouženým účinkem MeSH
• placeba MeSH
• tobolky MeSH

Ivermectin is an antiparasitic drug widely used in veterinary and human medicine. We have found earlier that repeated treatments of rats with high doses of this drug led to significant increase of cytochrome P450-dependent 7-methoxyresorufin O-demethylase (MROD) and 7-ethoxyresorufin O-deethylase (EROD) activities in hepatic microsomes. In the present study, the effects of ivermectin on cytochrome P450 (CYP) activities were investigated in mouflon (Ovis musimon) and fallow deer (Dama dama). This study was conducted also to point out general lack of information on both basal levels of CYP enzymes and their inducibilities by veterinary drugs in wild ruminants. Liver microsomes were prepared from control animals, mouflons, after single or repeated (six doses in six consecutive days) treatments with therapeutic doses of ivermectin (0.5 mg kg(-1) of body weight), and fallow deer exposed to repeated doses of ivermectin under the same conditions. Alkyloxyresorufins, testosterone and chlorzoxazone were used as the specific substrate probes of activities of the CYP isoenzymes. A single therapeutic dose of ivermectin significantly induced (300-400% of the control group) the activities of all alkyloxyresorufin dealkylases tested in mouflon liver microsomes. Repeated doses of ivermectin also caused an increase of these activities, but due to fair inter-individual differences, this increase was not significant. The administration of ivermectin led to an induction (170-210% of the control) of the testosterone 6beta- and 16alpha-hydroxylase activities in mouflon liver but no significant modulation of chlorzoxazone hydroxylase (CZXOH) activity was found in mouflon liver. CYP-dependent activities in hepatic microsomes were generally higher in fallow deer than in mouflons. However, with the exception of slight increase in the 7-benzyloxyresorufin O-dealkylase (BROD) activities, no significant modulation of the other activities was observed. The induction of CYP3A-like isoenzyme was confirmed by immunoblotting only in the microsomes from mouflons administered with repeated doses of ivermectin; however, no significant increase of CYP1A isoenzymes was observed due to a weak cross-reactivity of anti-rat CYP1A1/2 polyclonal antibodies used in the study. The results indicate that ivermectin should be considered as an inducer of several cytochrome P450 isoenzymes, including CYP1A, 2B and 3A subfamilies, in mouflons. The comparison of induction effect of ivermectin in rat, mouflon and fallow deer also demonstrates the inter-species differences in inducibility of CYP enzymes.

• MeSH
• anthelmintika aplikace a dávkování   farmakologie   MeSH
• aromatické hydroxylasy * MeSH
• cytochrom P450 CYP2C8 MeSH
• cytochrom P450 CYP2C9 MeSH
• enzymová indukce MeSH
• frakcionace buněk MeSH
• imunoblotting MeSH
• ivermektin aplikace a dávkování   farmakologie   MeSH
• izoenzymy metabolismus   MeSH
• jaterní mikrozomy účinky léků   enzymologie   MeSH
• lidé MeSH
• molekulární struktura MeSH
• přežvýkavci metabolismus   MeSH
• rodina 2 cytochromů P450 MeSH
• steroid-16-alfa-hydroxylasa MeSH
• steroidhydroxylasy metabolismus   MeSH
• systém (enzymů) cytochromů P-450 metabolismus   MeSH
• vysoká zvěř metabolismus   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• anthelmintika MeSH
• aromatické hydroxylasy * MeSH
• CYP2C11 protein, rat MeSH Prohlížeč
• CYP2C8 protein, human MeSH Prohlížeč
• CYP2C9 protein, human MeSH Prohlížeč
• cytochrom P450 CYP2C8 MeSH
• cytochrom P450 CYP2C9 MeSH
• ivermektin MeSH
• izoenzymy MeSH
• rodina 2 cytochromů P450 MeSH
• steroid-16-alfa-hydroxylasa MeSH
• steroidhydroxylasy MeSH
• systém (enzymů) cytochromů P-450 MeSH
• testosterone 7-alpha-hydroxylase, hamster MeSH Prohlížeč

During the direct handling with mouflon the ivermectin (IVM) is usually parenterally administered. The used dose is equal to dose recommended to domestic sheep (0.20 mg/kg of body weight). The qualitative and quantitative parasithological differences between domestic and wild sheep (mouflon) exist (Vyslouzil, 1985; Lochman et al., 1979; Boch and Supperer, 1992). The verification of real anthelmintic efficacy in IVM treatment of mouflon was not realized up to now. The aim of this study was to describe anthelmintic efficacy of IVM administered in different doses and to select the optimum dose. The study was realized during winter season in game herd in 23 mouflons of 10-11 months old. Before treatment larvae of Muellerius capillaries (strong infection) and eggs of Nematodirus spp. and Oesophagostomum spp. (mild infection) in common faecal samples were found. The mouflons were randomly divided in four groups control group (3 head) and 3 experimental groups (6-8 animals in group). Before experimental treatment each animal in experimental groups was weighted and marked. The doses of IVM 0.20, 0.60, and 1.00 mg/kg of body weight were used. The drug was administered subcutaneously. All mouflons were placed into enclosured area of 4 hectare. 28-60 days after treatment mouflon were hunted and detail helminthological examinations (lung macroscopical evaluation, larvoscopy of lung verminous spots, larvoscopy and ovoscopy of individual faeces, necropsy of gastrointestinal organs and quantification of nematode adults) were carried out, LPG and EPG values were determined. The study was realized as a simple blind experiment--all helminthological examinations were done without knowledge of the used therapy (control x experimental animals) or IVM dose (experimental animals). Macroscopical examinations of lungs showed symptoms of strong M. capillaries infection (numerous verminous spots) in all 23 mouflons. Larvoscopical examinations (lung tissue, individual faeces) after treatment became negative in 19 treated animals, in the rest of animals the mild larvoscopical finding was determined (Tab. I). Pretreatment common LPG values (ca 2100-2230) in control animals were confirmed, findings in verminous spots of these animals were highly positive (massive presence of live larvae, eggs, and rests of nematode adults). The qualitative findings (quantitatively were findings under the detection limit for the used method) were minimum in 4 mouflons of all treated groups. Pretreatment ovoscopical findings in control animals were confirmed, too. Necropsy examinations of gastrointestinal organs were highly positive in all control animals (mean finding of 95 adults of determined nematodes), in treated animals the findings were positive in 3 animals of different groups (up to 2 adults only). In respect to reached results, pathogenicity of found nematodes, age of experimental mouflons, and economy of treatment, a dose of 0.60 mg/kg of body weight IVM dose as a optimum for parenteral treatment of mouflon nematodoses is recommended.

• MeSH
• antinematodní látky aplikace a dávkování   MeSH
• divoká zvířata * MeSH
• injekce subkutánní MeSH
• ivermektin aplikace a dávkování   MeSH
• nematodózy farmakoterapie   veterinární   MeSH
• nemoci ovcí farmakoterapie   MeSH
• ovce MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• anglický abstrakt MeSH
• časopisecké články MeSH
• klinické zkoušky MeSH
• randomizované kontrolované studie MeSH
• Názvy látek
• antinematodní látky MeSH
• ivermektin MeSH

Hypodermosis and cephenemyiosis are largely widespread diseases in roe deer in the conditions of the Czech Republic. Both kinds of parasitosis cause great losses of game. The aim of this study was to test peroral administration of ivermectin with respect to the control of larval stages of hypodermosis (Hypoderma diana B.) in roe deer. Studies were performed on three localities within one three-year study and two 18-month studies. Ivermectin was administered for two days at a daily dose of 0.30 mg/kg body weight during winter game feeding. The shot deer were checked for the presence of larvae throughout the year. Prevalence and intensity of infection were determined. A total of 147 animals were checked in 1992-1994 (Tab.I); prevalence and intensity of infection were very low in comparison with the situation before treatment and with the control group (1994). Similar results were obtained in both shorter studies (Tab. II) performed on 27 animals in total. The results suggest (on the base of detail discussion) that the low values of prevalence and intensity of infection should be taken as partly distorted due to the methodical conditions of checks. The efficacy of ivermectin treatment was complemented by observation of several cases and their results employing direct checks of shot deer (Tab. III), including a six-year observation of a group of 6 to 10 individuals of tame deer treated year by. These results explicitly document the high efficacy of mass peroral ivermectin administration in the control of warble fly larvae. Ivermectin is the first drug suitable for the treatment of roe deer hypodermosis.

• MeSH
• aplikace orální MeSH
• Diptera účinky léků   MeSH
• hypodermyiáza farmakoterapie   parazitologie   veterinární   MeSH
• insekticidy aplikace a dávkování   MeSH
• ivermektin aplikace a dávkování   MeSH
• larva účinky léků   MeSH
• vysoká zvěř parazitologie   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• anglický abstrakt MeSH
• časopisecké články MeSH
• Názvy látek
• insekticidy MeSH
• ivermektin MeSH

Effect of ivermectin injected subcutaneously in a single dose on the serum specific antibody activity against. Psoroptes cuniculi antigens was studied on four heavily and three weakly P. cuniculi infested rabbits. It has been shown that ivermectin enhanced the production of the specific antibody, especially in weakly infested rabbits. The serum specific antibody activity in both heavily and weakly infested rabbits reached the peak levels on fifth after injection of ivermectin.

• MeSH
• infestace roztoči farmakoterapie   imunologie   veterinární   MeSH
• injekce subkutánní veterinární   MeSH
• ivermektin aplikace a dávkování   farmakologie   terapeutické užití   MeSH
• králíci parazitologie   MeSH
• roztoči imunologie   MeSH
• tvorba protilátek účinky léků   MeSH
• zvířata MeSH
• Check Tag
• králíci parazitologie   MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• ivermektin MeSH