The Experts below are selected from a list of 5283 Experts worldwide ranked by ideXlab platform
Sunil Dogra - One of the best experts on this subject based on the ideXlab platform.
-
efficacy and safety of Acitretin in three fixed doses of 25 35 and 50 mg in adult patients with severe plaque type psoriasis a randomized double blind parallel group dose ranging study
Journal of The European Academy of Dermatology and Venereology, 2013Co-Authors: Sunil Dogra, A Jain, Amrinder J KanwarAbstract:Background Acitretin is available for use in psoriasis since the late 1980s; however, there is no consensus on its optimum effective dose with acceptable side-effects. Objective To evaluate the efficacy and safety of Acitretin in three fixed doses in adult patients with severe plaque type psoriasis. Methods This was a randomized, double blind, parallel group, dose ranging study. The study included patients of either gender (age range, 18–65 years) with severe chronic plaque type psoriasis. Of the 80 patients screened, 61 were randomly assigned to three groups: group A – 20 patients (Acitretin 25 mg/day), group B – 20 patients (Acitretin 35 mg/day) and group C – 21 patients (Acitretin 50 mg/day) for 12 weeks. Forty-eight patients completed the study. The main outcome measure was change in Psoriasis Area Severity Index (PASI) score between the three groups from baseline to 12 weeks. Results After 12 weeks of therapy, the percentage reduction in the PASI score was 54%, 76% and 54% in Acitretin 25, 35 and 50 mg/day group respectively. PASI 75 was achieved in 47%, 69% and 53% patients in Acitretin 25, 35 and 50 mg/day groups respectively. The majority of adverse events were mucocutaneous, mild-to-moderate severity and dose dependent. Conclusions Acitretin 35 mg/day was observed to be more efficacious compared to 25 mg/day and 50 mg/day dosing, whereas its safety profile is better than 50 mg/day dosing in the management of severe plaque type psoriasis in adult patients.
-
efficacy and safety of combination Acitretin and pioglitazone therapy in patients with moderate to severe chronic plaque type psoriasis a randomized double blind placebo controlled clinical trial
Archives of Dermatology, 2009Co-Authors: Rajan Mittal, Samir Malhotra, P Pandhi, Inderjeet Kaur, Sunil DograAbstract:Objective To evaluate the efficacy and safety of combination therapy with Acitretin and pioglitazone hydrochloride in patients with moderate to severe chronic plaque-type psoriasis. Design Randomized, double-blind, placebo-controlled clinical trial. Setting A tertiary care referral hospital. Patients The study included patients of either sex (age range, 18-65 years) with moderate to severe chronic plaque-type psoriasis. Patients were excluded if they were of child-bearing potential or if they had impaired liver or renal function, hyperlipidemia, diabetes mellitus, coronary artery disease, or a body mass index greater than 30 (calculated as weight in kilograms divided by height in meters squared). Of the 62 patients screened, 41 were randomly assigned to 2 groups: 22 to an Acitretin (25 mg) plus placebo group and 19 to an Acitretin (25 mg) plus pioglitazone hydrochloride (15 mg) group. Main Outcome Measure Change in Psoriasis Area and Severity Index score between the 2 groups from baseline to 12 weeks. Results After 12 weeks of therapy, the percentage of reduction in the Psoriasis Area and Severity Index score was 64.2% in the Acitretin plus pioglitazone group and 51.7% in the Acitretin plus placebo group. The majority of the adverse events were mild to moderate except for 1 possibly unrelated episode of acute myocardial infarction in a 49-year-old woman in the Acitretin plus placebo group. Conclusions Pioglitazone has a potential beneficial antipsoriatic effect and may provide a convenient, efficacious, and relatively safe option to combine with Acitretin, although further studies are needed. Trial Registration clinicaltrials.gov Identifier:NCT00395941
P Fritsch - One of the best experts on this subject based on the ideXlab platform.
-
photochemotherapy for severe psoriasis without or in combination with Acitretin a randomized double blind comparison study
Journal of The American Academy of Dermatology, 1991Co-Authors: Adrian Tanew, J.-m. Geiger, A Guggenbichler, Herbert Honigsmann, P FritschAbstract:In a randomized, double-blind comparative study 60 patients with severe, widespread psoriasis were treated either with photochemotherapy (PUVA) alone or in combination with Acitretin. Forty-eight patients completed the study; of these, 25 received placebo combined with PUVA and 23 received Acitretin with PUVA. Marked or complete clearing of psoriasis occurred in 80% of the patients (20 of 25) without Acitretin and in 96% of the patients (22 of 23) with adjunctive Acitretin administration. The mean cumulative UVA dose given to patients in the Acitretin-PUVA group was 42% less than that required for patients in the placebo-PUVA group. We conclude that Acitretin substantially augments the efficacy of photochemotherapy in the treatment of severe psoriasis.
J.-m. Geiger - One of the best experts on this subject based on the ideXlab platform.
-
Determination of Acitretin in the Skin, in the Suction Blister, and in Plasma of Human Volunteers after Multiple Oral Dosing
Journal of Pharmaceutical Sciences, 1994Co-Authors: Jean-philippe Laugier, Hot Bun, Christian Surber, J.-m. Geiger, Klaus-peter Wilhelm, Alain Durand, Howard I. MaibachAbstract:Several HPLC methods for quantification of Acitretin and its 13‐cis isomer in biological fluids have been described. Only limited data are available on determination of this drug in skin samples. Our objective was to improve the sensitivity and selectivity of existing methods to measure drug in small skin samples from humans treated with Acitretin. With a new optimized mobile phase [methanol: acetonitrile (7:3, v/v), purified water with 1.5% (v/v) acetic acid, mixed in a 85:15 ratio (v/v)] and a new internal standard (arotinoid ethyl sulfone), a limit of quantification of 1 ng/g tissue was reached. Nine male volunteers were given an oral daily dose of 50 mg Acitretin for up to 28 days. Blood and skin samples (punch and shave biopsies, suction blister skin, and fluid) were taken at various time points during and after treatment. Drug concentration and metabolism in plasma and skin samples appeared to be linked in that the trans‐isomer concentration was always higher than the cis‐isomer concentration during dosing and 3 h after the last dose. However, 7 and 14 days after the last dose in plasma and in all tissue samples (except the shave biopsy), the all‐trans‐Acitretin concentration rapidly decreased and approached the detection limit. In the shave biopsy, the all‐trans‐Acitretin concentration remained higher than the 13‐cis‐Acitretin concentration. Furthermore, the elimination of two isomers from the shave biopsy was delayed. Our HPLC method has provided a suitable tool for pharmacokinetic and drug monitoring studies of all‐trans‐Acitretin and 13‐cis‐Acitretin that can be performed by any laboratory with a darkroom and a basic isocratic HPLC system.
-
Acitretin biotransformation into etretinate: role of ethanol on in vitro hepatic metabolism.
Dermatology (Basel Switzerland), 1994Co-Authors: Jean-philippe Laugier, Hot Bun, Christian Surber, J.-m. Geiger, G. De Sousa, Roger RahmaniAbstract:The aim of this study was to investigate the possible esterification of Acitretin into etretinate by using hepatocytes in primary culture from the rat, monkey, dog and man. With rat and human hepatocytes, etretinate was detectable only when ethanol was co-administered with Acitretin. With monkey and dog cells, traces of etretinate were found without ethanol addition, but the esterification of Acitretin was highly enhanced by ethanol. The metabolic profile was not changed when cells were pre-incubated with ethanol. Therefore Acitretin seems to act rather as a substrate than an enzymatic inducer.
-
Distribution of Acitretin in human skin
Annales de dermatologie et de venereologie, 1993Co-Authors: Christian Surber, Jean-philippe Laugier, J.-m. Geiger, Alain Durand, T. Rufli, Howard I. MaibachAbstract:Acitretin has recently been introduced for the systemic treatment of dermatologic diseases such as psoriasis and congenital disorders of keratinization. At present, only an oral form of this drug is available. However results from recent studies have shown that considerable drug concentrations can be delivered to the skin by topical administration of Acitretin. Based on this data we addressed the question whether the topical administration of Acitretin can produce in humans a drug concentration in the skin which exceeds the drug concentration that is found in the skin after multiple oral Acitretin dosing and is reported to be clinical effective. Drug concentrations in the skin were investigated under conditions in which the maximum dose that can be administered in a therapeutic situation was applied. Additionally, three different skin sampling techniques, the punch biopsy, the shave biopsy and the suction blister technique were validated to quantitate Acitretin in the skin. The drug concentrations in skin after systemic application in a steady state situation were comparable with the drug concentration reached after a single 24 hours topical application of a saturated Acitretin/isopropylmyristate formulation. However, no unequivocal effects in psoriasis and disorders of keratinization were observed up to now by the topical administration of Acitretin. The inverse drug concentration gradients which are present in the skin, depending on the route of administration, may explain differences in activity. The skin samples in our and other studies were homogenized or dissolved and thus much of the anatomical information is lost. The latter may be most important for the understanding of the local events.
-
photochemotherapy for severe psoriasis without or in combination with Acitretin a randomized double blind comparison study
Journal of The American Academy of Dermatology, 1991Co-Authors: Adrian Tanew, J.-m. Geiger, A Guggenbichler, Herbert Honigsmann, P FritschAbstract:In a randomized, double-blind comparative study 60 patients with severe, widespread psoriasis were treated either with photochemotherapy (PUVA) alone or in combination with Acitretin. Forty-eight patients completed the study; of these, 25 received placebo combined with PUVA and 23 received Acitretin with PUVA. Marked or complete clearing of psoriasis occurred in 80% of the patients (20 of 25) without Acitretin and in 96% of the patients (22 of 23) with adjunctive Acitretin administration. The mean cumulative UVA dose given to patients in the Acitretin-PUVA group was 42% less than that required for patients in the placebo-PUVA group. We conclude that Acitretin substantially augments the efficacy of photochemotherapy in the treatment of severe psoriasis.
Robert B. Armstrong - One of the best experts on this subject based on the ideXlab platform.
-
Effects of Acitretin on the liver.
Journal of the American Academy of Dermatology, 1999Co-Authors: Henry H. Roenigk, Nicholas J. Lowe, Jeffrey P. Callen, Cynthia Guzzo, H. Irving Katz, K. C. Madison, Thomas P. Nigra, Virginia C. Fiedler, Robert B. ArmstrongAbstract:Background: Therapy with aromatic retinoids for psoriasis is associated with abnormal liver function test findings and toxic hepatitis (in 1.5% of patients). Objective: Our purpose was to determine the safety of Acitretin with respect to liver function, on the basis of biopsy. Methods: We treated 128 adults (with chronic, stable psoriasis) with oral Acitretin (25–75 mg/day) for four 6-month intervals in a prospective, open-label, 2-year multicenter study. Liver biopsies were performed before and after study completion (2 years). Results: Eighty-three available pairs of pretreatment and posttreatment liver biopsies demonstrated no change in 49 patients (59%), improvement in 20 (24%), and worsening in 14 (17%). Of these 14 patients with decrements in biopsy status, most changes were mild. There was no correlation between liver function test abnormalities or cumulative Acitretin dose and changes in liver biopsy status. Conclusion: Acitretin therapy elicited no biopsy-proven hepatotoxicity in this prospective 2-year study. These findings suggest that periodic liver biopsy may not be necessary with Acitretin treatment.
-
Acitretin plus UVB therapy for psoriasis. Comparisons with placebo plus UVB and Acitretin alone.
Journal of the American Academy of Dermatology, 1991Co-Authors: Nicholas J. Lowe, Janet H. Prystowsky, Teresa Bourget, Joseph Edelstein, S. G. Nychay, Robert B. ArmstrongAbstract:UVB radiation is beneficial for the treatment of psoriasis vulgaris. Patients with recalcitrant disease, however, are slow to respond to UVB phototherapy with and without the use of coal tars or emollients. Etretinate and, more recently, Acitretin have proved useful, but clinical improvement is slow when they are used as monotherapy in plaque psoriasis. Each drug also produces side effects, some of which are dose related. This study was designed to compare results of treatment with UVB combined with either Acitretin (50 mg/day) or placebo to determine if psoriasis would respond faster and to less cumulative exposure to UVB and Acitretin. The psoriatic disease cleared to a greater degree in patients treated with Acitretin-UVB with fewer treatments and smaller amounts of UVB radiation than in patients treated with either placebo-UVB or Acitretin alone.
A. Kint - One of the best experts on this subject based on the ideXlab platform.
-
Skin, adipose tissue and plasma levels of Acitretin with rare occurrence of esterified Acitretin during long-term treatment.
Acta dermato-venereologica, 1993Co-Authors: Evelyne Meyer, Willy E. Lambert, J. De Bersaques, A.p. De Leenheer, A. KintAbstract:In a previous study Acitretin and its 13-cis-metabolite were monitored in the plasma and epidermis of healthy volunteers. They were given 50 mg of trans-Acitretin daily. No drug accumulation was observed in the skin, nor in the plasma. The purpose of the present study was to extend the data from non-psoriatic to psoriatic (n = 11) subjects, treated for at least 1 month with 25 mg Acitretin. Plasma, skin biopsies and subcutaneous fat samples were analysed using HPLC. Trough levels of Acitretin in skin were below the quantification limit, increasing to 28 +/- 16 ng/g within 5 h after dosing. Fat tissue levels exceeded those of skin, with values of 98 +/- 71 ng/g within 5 h after drug intake. In 2 patients, additional samples were taken 3 days post-therapy. Here, concentrations were below the quantification limit in adipose tissue, confirming that Acitretin is not stored in subcutaneous fat. Esterification of Acitretin into etretinate was observed in 2 subjects. This observation illustrates the recently described new metabolic pathway for Acitretin. On both occasions, the unexpected ethylester metabolite was extensively stored in fat tissue.
-
The distribution of cis- and trans-Acitretin in human epidermis.
British journal of clinical pharmacology, 1992Co-Authors: Evelyne Meyer, Willy E. Lambert, J. De Bersaques, A.p. De Leenheer, A. KintAbstract:The concentrations of trans-Acitretin and its principal metabolite, cis-Acitretin, were measured by h.p.l.c. after single and multiple dosing (50 mg orally for 13 days) in plasma, blister fluid and epidermal samples from four healthy male volunteers. Within-day epidermal concentrations of trans-Acitretin exceeded those of the cis-form which were at the limit of assay sensitivity. No accumulation of trans-Acitretin was observed in plasma or blister fluid but AUC values for the drug in blister roof cells tended to be higher after multiple dosing.