ISSN:0954-6634    

DOI:10.3109/09546639209092764

出版商:Taylor&Francis    

年代:1992

数据来源: Taylor

摘要:

Advantan* is a new potent corticoid preparation that has been specially developed for the local treatment of eczematous dermatoses. The active ingredient of Advantan is methylprednisolone aceponate (MPA), a nonhalogenated corticoid diester. Advantan has been developed in three different formulations (cream, ointment, fatty ointment). Pharmacological studies have shown that the potency of MPA in the skin after dermal application is almost equivalent to that of Cvalerate and clobetasol propionate, and exceeds that of hydrocortisone butyrate. The toxicological programme provided no grounds for doubting the safety of products containing MPA, when used as directed. Like all other corticoids, MPA exerts its action via an intracellular receptor but its pharmacokinetic properties differ from those of other corticoids in that it leads to a high degree of dissociation between topical and systemic action. As a result of the two-fold esterification, MPA is highly lipophilic. Thus, it penetrates readily into the skin where it is hydrolysed forming 6α-methylprednisolone 17-propionate. For an understanding of the high local activity of MPA it is of importance to know that the product of the hydrolysis is a stronger corticoid than MPA. On absorption into the blood the metabolite is rapidly inactivated by conjugation with c acid, which explains the low systemic activity of MPA.

ISSN:0954-6634    

DOI:10.3109/09546639209092765

出版商:Taylor&Francis    

年代:1992

数据来源: Taylor

ISSN:0954-6634    

DOI:10.3109/09546639209092766

出版商:Taylor&Francis    

年代:1992

数据来源: Taylor

摘要:

Methylprednisolone aceponate (MPA, Advantan*) is a new corticosteroid diester developed for the topical treatment of steroid-responsive skin diseases. It is readily hydrolyzed in the skin resulting in its activation, and on absorption into the blood, the metabolites are rapidly inactivated by conjugation with glucuronic acid thus minimizing systemic corticoid effects. 276 patients suffering from atopic dermatitis with symmetrically distributed lesions were enrolled in three double-blind controlled right/left half-side trials comparing: (1) 0.1% MPA twice daily with MPA once daily (n= 88); (2) 0.1% betamethasone valerate (BMV) twice daily (n= 94); and (3) 0.1% MPA once daily with 0.1% BMV twice daily (n= 94). There were no differences between MPA used once and twice daily, respectively, with 66% complete healing and 27% marked inprovement (overall response rate 93%) as compared with BMV twice daily with 68% complete healing and 30% marked improvement (response rate 98%). The local and systemic tolerance was excellent.

ISSN:0954-6634    

DOI:10.3109/09546639209092767

出版商:Taylor&Francis    

年代:1992

数据来源: Taylor

摘要:

Effectiveness and side-effects of the new topical halogenfree corticosteroid methylprednisolone aceponate (MPA) (0.1% in commercial o/w or w/o emulsions) were tested in six multicentre controlled double-blind studies, using betamethasone valerate (BMV) as control (0.1% in o/w emulsion); a total of 1723 patients with various kinds of eczema were included into these studies. Treatment was carried out for a maximum of 3 weeks; the choice of vehicle (w/o or o/w emulsion) was left for the attending physicians to decide. In addition, effectiveness of 1×/day application of MPA as compared to 2×/day and to 2×/day of BMV was investigated. The following conclusions can be drawn from these studies:1. All regimens tested proved approximately equally effective, more than 90% of the patients being symptom-free or greatly improved after 3 weeks.2. MPA in cream and ointment performed equally well.3. 1×/day application of MPA was equally effective as 2×/day MPA and 2×/day BMV.4. Tolerability was excellent; systemic side-effects were not observed; mild to moderate local complaints were reported in 5% of patients in all groups.

ISSN:0954-6634    

DOI:10.3109/09546639209092768

出版商:Taylor&Francis    

年代:1992

数据来源: Taylor

摘要:

Many side effects, both local or systemic, may result from topical steroid therapy, especially after long-lasting treatment with potent corticosteroids. Of particular importance are the depression of the hypothalamic pituitary adrenal axis and the local side-effects from topical application consisting mainly of skin atrophy. Advantan* is a new potent corticoid preparation that has been specially developed for the local treatment of corticoid-responsive dermatoses. The active ingredient is methylprednisolone aceponate (MPA). It should be noted that the local tolerance and the presence of systemic side-effects of MPA have been extensively investigated in healthy volunteers and have also been studied in patients.Animal studies (rats, rabbits) indicated that MPA can be classified as a corticoid with low atrophogenic potential. In a comparative study to evalute the atrophogenic potential of MPA in man, after long-term topical application in healthy volunteers under occlusive conditions (Duhring chamber), the three formulations with MPA (0.1% cream, ointment, fatty ointment) developed a significantly lower atrophogenic potential than a product containing clobetasol 17-propionate. Another conclusion was that the atrophogenic potential of MPA was comparable to that of betamethasone 17-valerate. This was confirmed by clinical trials. In 1145 patients suffering from various types of eczema who used MPA in cream and ointment, mild atrophy of the skin was observed in only one patient. Moreover, clinical signs of atrophy were present in only two out of a group of 673 patients (590 adult and 83 children) treated with MPA fatty ointment. In a group of 66 patients who used this same MPA fatty ointment during 3–4 months, no signs of skin atrophy were observed. Folliculitis or pustules occurred only in a small number of patients.Double-blind studies in 200 healthy volunteers with the three preparations of MPA, and their corticosteroid free bases revealed a low level of local adverse effects. Local adverse effects including the subjective complaints itching or burning as well as erythema, exsiccation, weeping, papules/ vesicles, fissures etc were reported in 5 to 6% of the patients, but led to a premature discontinuation of therapy in less than 1% of the treated patients. Systemic side effects have not been reported in patients treated to MPA.In 100 healthy adult volunteers treated intensively with 40 g of topical 0.1% MPA (three formulations) daily on 60% of the body surface under occlusion over 5 or 8 days, the cortisol levels always remained within the normal range and the circadian rhythm was maintained in all subjects. In patients receiving extensive treatment with MPA in psoriatic skin and in atopic dermatitis, the values for plasma cortisol slightly decreased but remained in the normal range while the circadian rhythm of the release of endogenous cortisol remained unchanged.These results suggest that MPA 0.1% cream, ointment and fatty ointment are safe. No serious or lasting adverse effects occurred. Infection of the skin will of course limit the application of MPA as with other topical glucocorticosteroids. The development of atrophy and telangiectasia will have to be carefully monitored. With regard to other adverse effects, 0.1% MPA compared well with the widely prescribed standard preparations of betamethasone 17-valerate. It can be concluded that because of the proven therapeutic efficacy, the excellent tolerance and the low systemic activity the risk/benefit ratio is very favourable for MPA.

ISSN:0954-6634    

DOI:10.3109/09546639209092769

出版商:Taylor&Francis    

年代:1992

数据来源: Taylor

ISSN:0954-6634    

DOI:10.3109/09546639209092770

出版商:Taylor&Francis    

年代:1992

数据来源: Taylor