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PubMed1997

Acitretin therapy is effective for psoriasis associated with human immunodeficiency virus infection.

OBJECTIVE: To determine the safety, tolerability, and effectiveness of a newer retinoid, acitretin, as monotherapy for psoriasis associated with human immunodeficiency virus infection (PS-HIV). DESIGN: Pilot investigation. SETTING: An academic medical center. PATIENTS: Eleven patients selected from volunteers with PS-HIV were enrolled in a 20-week treatment protocol. Two patients discontinued participation in the study because of worsening psoriasis; a third patient was unable to continue treatment after having a myocardial infarction, presumably unrelated to acitretin therapy. INTERVENTION: Each patient received an optimized dose of acitretin during the period of observation. Clinical and laboratory assessments were performed every 2 weeks during the trial. MAIN OUTCOME MEASURES: The Psoriasis Area and Severity Index was used to assess the clinical response to treatment. To monitor for toxic drug effects, a panel of laboratory parameters, including complete blood cell count, biochemistry profile, urinalysis, HLA typing, skin biopsy for histological examination, and T-cell counts, was performed. RESULTS: Six (54%) of 11 patients with PS-HIV achieved good to excellent responses using acitretin monotherapy. Four patients (36%) achieved complete clearing. There was no evidence of a correlation between the pretreatment measures of immunosuppression and the therapeutic response. Parameters of immunosuppression were not exacerbated by acitretin therapy. CONCLUSIONS: Acitretin is a safe and effective treatment for PS-HIV. Both skin and joint manifestations of PS-HIV responded to acitretin therapy in most patients. Optimal results were achieved with a dose of 75 mg/d. The adverse effects were moderate and well tolerated. Acitretin does not appear to have immunosuppressive properties. A formal randomized clinical trial is warranted.

Acitretin↗
PubMed2004

Acitretin embryopathy: a case report.

BACKGROUND: Acitretin is an aromatic retinoid analog of vitamin A. Drugs of this group are well-known teratogenic agents. Nevertheless, acitretin embryopathy has been described only in fetuses. CASE: An infant was exposed to 10 mg/day of acitretin from the beginning of pregnancy until the 10th gestational week. At term, the newborn showed the following abnormalities: microcephaly, epicanthal folds, low nasal bridge, high palate, cup-shaped ears, anteverted nostrils, atrial septal defect, and bilateral sensorineural deafness. At 18 months of age, the patient showed microcephaly and neurodevelopmental delay. CONCLUSIONS: Our patient shows a pattern of anomalies resembling that observed in isotretinoin- and etretinate-exposed children. After ingestion, acitretin is partially converted into etretinate, and etretinate is partially metabolized into acitretin. A similar phenotype would therefore be expected after prenatal exposure to either drug. Moreover, in the present case, teratogenic effects were observed even though the dose was lower than in the previously reported acitretin embryopathy cases. Therefore, we propose that different retinoids, acitretin included, produce only one malformation pattern with variable phenotypic expression.

Abnormalities, Multiple↗
PubMed1990

Pharmacokinetic profile of two aromatic retinoids (etretinate and acitretin) in the obese Zucker rat.

Etretinate accumulates in adipose tissue; this appears to account for its long terminal elimination phase in psoriatic patients. The purpose of the present study was to investigate the pharmacokinetic profile of etretinate and acitretin in a genetically obese rodent model, the Zucker rat. Pairs of obese and lean Zucker rats were dosed intravenously (0.5 mg/kg) and blood samples were collected. Plasma concentrations of etretinate and its major metabolites, acitretin and the cis isomer of acitretin (isoacitretin), were assayed by HPLC. The systemic clearance (CLs) of etretinate and the formation clearance (CLf) of the metabolite (acitretin) were lower in the obese rats (132 and 62.4 mL/min, respectively) compared with their lean littermates (197 and 126 mL/min, respectively). The remaining metabolic clearance (CLd) was identical for the lean and obese animals (70.9 and 69.9 mL/min, respectively). The ratio of metabolite-to-parent drug area under the plasma concentration-time curve (i.e., acitretin:etretinate) in the obese animal was less than that value in the lean animals (0.348 versus 0.811, respectively) following the administration of etretinate. Despite a doubling in the mean value (204 versus 87.9 mL), no statistically significant differences in the volume of distribution term for etretinate (Vdss) was observed in the obese animals, due to the large interanimal variability. The terminal phase half-life (t1/2) was significantly longer in the obese rats (3.52 versus 1.25 h). Following acitretin administration, no statistically significant differences were observed between the obese and lean animals for any of the parameters (CLs, Vdss, MRT, t1/2) of acitretin.(ABSTRACT TRUNCATED AT 250 WORDS)

Acitretin↗
PubMed1996

[Trans-acitretin is metabolized back to etretinate. Importance for oral retinoid therapy].

The oral retinoid etretinate (Tigason) has recently been replaced by trans-acitretin (Neotigason) in the treatment of severe psoriasis, primarily because of its short half-life and the assumption that a shorter period of subsequent contraception would be required. After introduction of the new drug, however, circulating quantities of etretinate were detected in patients treated with trans-acitretin. Thus far, re-esterification has been detected in at least 83 cases. The 2-month period of strict contraception initially recommended after oral intake of trans-acitretin has been extended to 2 years, as with etretinate. We review some aspects of trans-acitretin metabolism, with special emphasis on etretinate formation. Re-esterification of trans-acitretin into etretinate takes place under varying conditions in volunteers and patients, as well as in animal models. Ethanol is a co-factor for the enzymatic re-esterification of trans-acitretin. It is unclear whether the introduction of trans-acitretin has been of any significant benefit to patients. Monitoring of plasma retinoid levels during and after retinoid therapy remains of decisive importance in managing difficult cases and or in approving decisions for pregnancy.

Acitretin↗
PubMed2004

In vitro antigenotoxic potential of acitretin in human lymphocytes treated with the antineoplastic alkylating agent ASE (NSC-71964).

Acitretin is widely used in the systemic treatment of severe forms of psoriasis and other skin disorders. ASE, namely 3beta-hydroxy-13alpha-amino-13,17-seco-5alpha-androstan-17-oic-13,17-lactam-p-bis(2-chloro-ethyl)amino phenylacetate (AzaSteroidalEster, NSC-71964), is an alkylating agent with antineoplastic activity and mutagenic properties. The aim of this study was to investigate the possible genotoxic and/or antigenotoxic effects of acitretin in human lymphocyte cultures in vitro, using sister chromatid exchange (SCE) and cytokinesis-blocked micronucleus (CBMN) assays. Micronucleus (MN) analysis was achieved in combination with fluorescence in situ hybridization (FISH), using an alpha-satellite DNA pancentromeric probe. It was found that acitretin alone demonstrated no clastogenic or aneugenic activity. However, simultaneous incubation of lymphocyte cultures with ASE and acitretin resulted in a reduction of ASE-induced SCEs. For MN analysis lymphocytes were treated with ASE and acitretin at 21 and 41 h after culture initiation, corresponding to G1 and G2 phases, respectively, and lasted until cell harvest. Acitretin caused a decrease in ASE-induced MN when treatment of cells started at 41 h, but exerted no effect on them when treatment started at 21 h. These findings suggest that acitretin exerts antigenotoxic effects in human lymphocyte cultures, the expression of which may be related to the cycle phase of the cells upon onset and duration of the treatment, at least as far as MN frequency is concerned.

Acitretin↗
PubMed1992

Pharmacokinetics and drug interactions of etretinate and acitretin.

Acitretin, the metabolite of etretinate, is eliminated far more rapidly from the human body than is etretinate. It had therefore been suggested that only a short period of contraception would be required after the cessation of long-term therapy with acitretin. However, recent studies have demonstrated the presence of etretinate in the plasma of patients who were treated with acitretin. In this article we provide results from a study in our center and discuss earlier data in light of the recently discovered metabolic pathways for acitretin. Reesterification of acitretin to etretinate, however, results in a loss of the metabolic advantages of acitretin. Because of this situation the recommended contraception period after acitretin therapy has been lengthened to 2 years.

Acitretin↗
PubMed1989

Side-effect profile of acitretin therapy in psoriasis.

Acitretin, the principal and free acid metabolite of etretinate, was used to treat patients with stable, plaque-type psoriasis. For the first 8 weeks, 38 patients received placebo or acitretin, 10, 25, 50, or 75 mg daily, in a double-blind manner. After the double-blind phase, the patients were allowed to continue for a total of 6 months of acitretin therapy at an average dosage of 50 mg/day. When the patients flared after stopping therapy, an additional 6-month course of acitretin therapy was offered. Acitretin, which was as effective as etretinate, had to be given at a dosage of 50 mg/day or more to obtain a significant benefit. Side effects frequently occurred in patients receiving acitretin, 25 mg/day or more, but were generally mild and did not warrant discontinuation of therapy. They were similar to those of etretinate therapy; cheilitis, peeling of palms and soles, and alopecia occurred most frequently. The most common abnormal laboratory test results were elevations in serum triglycerides and, to a lesser extent, serum cholesterol and liver transaminase levels. Acitretin, in view of its much shorter half-life and similar efficacy and side-effect profile compared with etretinate, may be a preferable therapy for psoriasis, especially in women of childbearing age.

Acitretin↗
PubMed1993

In vivo skin penetration of acitretin in volunteers using three sampling techniques.

Etretinate and acitretin are given orally to treat psoriasis and various keratinization disorders. Acitretin, the main active metabolite of etretinate, has the pharmacokinetic advantage of being rapidly eliminated, but it shares etretinate's toxicologic profile. Thus a topical delivery of acitretin with no or reduced systemic adverse effects is desirable. To characterize the therapeutic potential of topically delivered acitretin, we quantitatively assessed its percutaneous penetration in healthy human volunteers. Additionally, three skin sampling techniques, the punch biopsy, the shave biopsy, and the suction blister technique, were validated to quantitate acitretin in the skin. The results suggest that topical delivery of acitretin renders skin concentrations which exceed those reported after oral administration of etretinate or acitretin. However, because of possible interlaminate drug contamination, drug localization within a particular skin compartment cannot be determined.

Acitretin↗
PubMed2003

Retrospective study of the efficacy of narrowband UVB and acitretin.

BACKGROUND: In this retrospective analysis the effect of narrowband ultraviolet B treatment in combination with acitretin is reviewed in 40 patients with plaque psoriasis. Narrowband UVB is highly effective for plaque psoriasis, but requires multiple phototherapy treatments, making patient compliance problematic. Oral acitretin is moderately effective as monotherapy, but when combined with ultraviolet B or PUVA, its use has reduced the number of treatments required for clearing, and has resulted in clearing of patients otherwise refractory to these phototherapeutic modalities. There is only sparse data on the combination of acitretin with narrowband UVB. We therefore analyzed data on 40 patients treated with this combination. RESULTS: The majority of patients treated had psoriasis that was refractory to treatment with broadband ultraviolet B, monotherapy with narrowband UVB, monotherapy with acitretin, or the combination of acitretin and broadband UVB. In this difficult-to-treat group of patients, the combination of low dose acitretin (25 mg po daily) and narrowband UVB three times per week resulted in greater than 75% improvement in 29 (72.5%) patients. Only 5 (12.5%) patients had less than 50% improvement. The combination was well tolerated and associated with typical retinoid and narrowband UVB side effects including elevation of serum lipids, burn and cheilitis. CONCLUSION: The combination of acitretin with narrowband UVB results in faster improvement even in more difficult-to-treat patients. In combination the treatments appear to have synergistic effects.

Acitretin↗
PubMed1993

Rapid effect of treatment of psoriatic erythrocytes with the synthetic retinoid acitretin to increase 8-azido cyclic AMP binding to the RI regulatory subunit.

We have recently demonstrated a deficiency in the cyclic adenosine monophosphate (cAMP)-dependent protein kinases (PKA), the intracellular mediator of AMP, in psoriasis. This enzyme defect is expressed in fibroblasts and in red blood cells isolated from psoriatic patients. In these cells, the abnormality noted in cAMP binding to PKA correlates well with the severity of the disease and is corrected by long-term treatment with etretinate. In this study, we determined the effect of oral administration of acitretin in four psoriatic patients on the altered cAMP binding observed with the RI regulatory subunit of PKA in erythrocytes prepared from these patients. Acitretin (30 mg/day) induced a rapid (within 1 h) increase in the ability of the RI regulatory subunit of erythrocytes to bind the 8-azido[32P]cAMP photoaffinity analogue of cAMP. The maximal plateau for this effect of acitretin was observed within 24 h of treatment and preceded the clinical improvement of the disease. The effect of acitretin was dose-dependent, with the maximal response observed at 40 mg acitretin/d. In addition, the rapid exposure (15 min) of erythrocytes isolated from untreated patients exhibiting severe psoriasis to acitretin also promoted an increase in binding of 8-azido[32P]cAMP to the RI cAMP binding protein. Retinoic acid and 13-cis-retinoic acid were as efficient as acitretin in inducing the increase in binding of 8-azido[32P]cAMP to the RI regulatory subunit, whereas arotinoid was without effect. These results suggest that acitretin may act to modify PKA (the RI regulatory subunit) at the post-transcriptional level, and this may reflect, in part, on the mechanism of action of this synthetic retinoid. Further, monitoring this biochemical event may be helpful in determining the choice of retinoid therapy and in the management of its pharmacology.

Acitretin↗
PubMed1992

Acitretin. A review of its pharmacology and therapeutic use.

Acitretin (etretin), a second generation monoaromatic retinoid for use in the treatment of severe psoriasis and other dermatoses, is the major active metabolite of etretinate and possesses a similar therapeutic index; i.e. a similar ratio of clinical efficacy to adverse effects. When used alone at a maintenance dosage of 30 to 50mg daily, acitretin is effective in the treatment of psoriasis, causing a reduction in the severity of scaling, erythema and induration. Efficacy appears to be further enhanced by combination with psoralen-ultraviolet A photochemotherapy (PUVA) or ultraviolet B irradiation (UVB). These combinations reduce the time to lesion clearance and reduce the total radiation dose, improving overall safety. Comparative studies have confirmed the equivalence of acitretin and etrtinate with regard to efficacy and toxicity. Adverse reactions are dose-related and generally typical of hypervitaminosis A. Alopecia and mucocutaneous symptoms such as cheilitis and drying of the mucous membranes are particularly prevalent. Hypertriglyceridaemia and elevation of cholesterol levels also occur. Examination of the pharmacokinetic profile of acitretin reveals its main advantage over etretinate. Acitretin is less lipophilic than etretinate, and its lack of sequestration into 'deep' fatty storage sites is reflected in a comparatively short terminal elimination half-life of 50 to 60 hours, compared with 120 days for etretinate. Due to its teratogenic potential, acitretin is strictly contraindicated in women of childbearing potential unless effective contraceptive measures are employed. Etretinate has been identified in plasma samples of some patients treated with acitretin. Thus, acetretin has an established place in the treatment of keratinising disorders, although its use in women of child-bearing potential must be accompanied by effective contraceptive measures, with a further 2-year contraceptive period after therapy completion.

Acitretin↗
PubMed2006

[Effects of acitretin on the expression of signaling pathway-related genes in epidermal squamous-cell carcinoma cells].

OBJECTIVE: To study the effects of acitretin on the expression of signaling pathway-related genes in an epidermal squamous-cell carcinoma cell line. METHODS: The mRNA expression levels of STAT3, cyclin D1 and p42/44MAPK were detected in a human epidermal carcinoma cell line A431 by RT-PCR. Their expressions at protein level were studied by Western blot. The expression levels were studied in cells treated with or without 10(-5) mol/L acitretin at different time intervals. RESULTS: (1) Acitretin could significantly inhibit the expression of STAT3 and cyclin D1 mRNA in a time-dependent manner (P < 0.05). The STAT3 and cyclin D1 protein expression levels were down-regulated. Acitretin could also down-regulate the p42/4MAPK mRNA expression. (2) After incubation with acitretin, the mRNA level of cyclin D1 cells was positively correlated with that of STAT3 (P < 0.05). The cyclin D1 protein level was also positively correlated with that of STAT3 (P < 0.05). However there was no correlation of mRNA levels between cyclin D1 and p42/44MAPK. CONCLUSION: Regulation of the Jak/STAT3 signaling pathway may play an important role in the effect of acitretin on epidermal squamous-cell carcinoma cells. The abnormal expression of STAT3 can be regarded as a prerequisite for acitretin treatment effect.

Acitretin↗
PubMedDate not supplied

Influence of pregnancy on the pharmacokinetic disposition of two aromatic retinoids (etretinate and acitretin) in the rat. I. Intravenous studies.

The influence of pregnancy on the disposition of two related aromatic retinoids (etretinate and its metabolite, acitretin) was evaluated in a rodent model. The plasma concentrations of etretinate and acitretin were monitored by a specific HPLC method following iv bolus doses to 17-day pregnant and nonpregnant Sprague-Dawley rats. The systemic clearance of etretinate was significantly lower in the pregnant rats compared to nonpregnant controls (129 vs. 185 ml/hr, respectively; p less than 0.05). This decrease was entirely due to a lower formation clearance of acitretin (acid) from etretinate (ester) in the pregnant animals (96 vs. 146 ml/hr; p less than 0.05). The in vitro plasma hydrolysis rate of etretinate was also lower in the pregnant animals. By contrast, the systemic clearance of acitretin was greater in the pregnant compared to the nonpregnant control animals (184 vs. 145 ml/hr, respectively; p less than 0.05). The apparent volumes of distribution for both retinoids were comparable in the pregnant and nonpregnant animals. Etretinate infusions in nonpregnant animals yielded systemic clearances (mean = 164 ml/hr) which were similar to those obtained for bolus dose experiments. Acitretin clearance increased (plasma levels decreased) following acitretin infusion to nonpregnant rats over the time course of the infusion. The results illustrate the marked effect of pregnancy on the disposition of these retinoids and suggest that acitretin may pose less of a teratogenic hazard than the parent compound etretinate.

Acitretin↗
PubMed1995

Use of acitretin for the skin complications in renal transplant recipients.

AIM: To review our experience using acitretin for the skin complications in renal transplant recipients. METHODS: Fifteen longterm caucasian renal transplant recipients suffering skin complications were treated with acitretin (10-50 mg daily), a second generation retinoid. Indications for its use were progressive actinic keratoses, widespread warts or recurrent skin malignancies. The therapeutic benefit was assessed by the general condition of of the skin and the number of skin malignancies excised, and the side effects by regular enquiry, skin examination and laboratory tests. RESULTS: All 15 patients reported that the skin became softer and smoother. Actinic keratoses and warts improved or disappeared. Six patients had been on acitretin for over 12 months. The number of malignancies decreased in four of these six patients. Nine patients had cutaneous side effects due to acitretin necessitating a reduction in dose in five patients and discontinuation in the remaining four patients. No patient had any disturbance of their liver or renal function tests or lipid profile. No interaction was found between cyclosporin A and acitretin (seven patients). CONCLUSIONS: Most patients treated with acitretin experienced subjective improvement and actinic keratoses and warts improved or disappeared. Its effect on the skin malignancy rate was variable. Acitretin was reasonably well tolerated. The benefits of this drug remain anecdotal, making a prospective, multicentre, placebo controlled study essential.

Acitretin↗
PubMed1996

An appraisal of acitretin therapy in children with inherited disorders of keratinization.

Retinoid therapy represents the treatment of choice for severe inherited disorders of keratinization. This paper reviews our experience of acitretin, compares acitretin with etretinate and defines guidelines for treatment. Forty-six children have received acitretin since 1992 in our hospital: 29 children had either lamellar ichthyosis (nine), non-bullous ichthyosiform erythroderma (five), bullous ichthyosiform erythroderma (four), Sjögren-Larsson syndrome (three) or another rare condition (eight). The other 17 children who had psoriasis (16) and extensive viral warts (one), were excluded. Data on efficacy and tolerability of retinoid therapy were available for all but one patient. The cumulative follow-up was 472 months for acitretin. The mean (+/- standard deviation) optimal dosage for acitretin was 0.47 +/- 0.17 mg/kg per day, and this did not significantly differ between disorders. The overall improvement was considerable, with only three patients responding poorly. Mild to moderate mucocutaneous dryness was frequent. Minor abnormalities of liver function tests (four patients) and triglycerides (one patient) never led to changes of therapy. Irreversible side-effects did not occur. Acitretin therapy for children with inherited keratinization disorders is best started at 0.5 mg/kg per day. It represents a safe and effective treatment, provided that the minimal effective dose is maintained and that side-effects are carefully monitored. When switching from etretinate to acitretin, a 20% reduction is recommended if the etretinate dose is over 0.75 mg/kg per day or if side-effects are dose limiting. Otherwise the same dose can be used.

Acitretin↗
PubMed1998

Prospective randomized multicenter clinical trial on the use of interferon -2a plus acitretin versus interferon -2a plus PUVA in patients with cutaneous T-cell lymphoma stages I and II.

Cutaneous T-cell lymphoma (CTCL) constitutes a malignant proliferative disease involving mostly CD4(+) T cells arising in the skin. Because of the lack of curative treatment options, interferons (IFN) have been introduced into the therapy of CTCL. Although effective even in advanced disease, response rates were about 50% and the duration of response was short. To improve the results of interferon monotherapy, combinations of IFN with oral photochemotherapy (PUVA) or retinoids were investigated in nonrandomized trials showing higher response rates. We have therefore conducted this prospective randomized multicenter trial to compare these two combination therapies, ie, IFN plus PUVA and IFN plus acitretin. IFN -2a was administered at 9 MU three times weekly subcutaneously in both groups, with lower increasing doses during the first week. Photochemotherapy was applied after oral intake of 8-methoxypsoralen (0.6 mg/kg body weight) 5x weekly during the first 4 weeks, 3x weekly from weeks 5 through 23, and 2x weekly from weeks 24 through 48, with escalating doses beginning with 0.25 J/cm2. Twenty-five milligrams of acitretin was administered daily during the first week, and 50 mg was administered from weeks 2 through 48. Of 98 patients randomized in this study, 82 stage I and II patients were evaluable: 40 in the IFN+PUVA group and 42 in the IFN+acitretin group. With 70% complete remissions in the IFN+PUVA group, this treatment was significantly superior to the IFN+acitretin group with only 38.1% complete remissions. Time to response was significantly shorter in the IFN+PUVA group, with 18.6 weeks compared with 21.8 weeks in the IFN+acitretin group. Side effects were mostly mild to moderate and did not differ significantly in both treatment groups. However, there were more adverse events leading to study discontinuation in the IFN+acitretin group. Based on these findings, we conclude that IFN plus oral photochemotherapy is superior to IFN plus acitretin, inducing more complete remissions in patients with CTCL stages I and II.

Acitretin↗
PubMed2003

Inclusion of acitretin into cyclodextrins: phase solubility, photostability, and physicochemical characterization.

Acitretin, a retinoid for the treatment of severe psoriasis, exhibits extremely low aqueous solubility and high photosensitivity. This study investigated the effects of the complexation of acitretin with the respective hydroxypropyl-beta-cyclodextrin (HPBCD) and randomly substituted methyl-beta-cyclodextrin (RMBCD) on the aqueous solubility and photostability of the drug. Phase-Solubility studies indicated that the solubility of acitretin was dramatically improved by formation of complexes and further increased by pH adjustment. Stability constants were much higher for acitretin complexed with RMBCD than with HPBCD. Both cyclodextrins acted to decrease degradation of acitretin in solution. The physicochemical properties of solid inclusion complexes were characterized by Fourier transform infrared spectroscopy, differential scanning calorimetry, and X-ray diffractometry. Molecular modeling with MMFF94s force field (SYBYL V6.6) was utilized to predict the preferred orientation of acitretin in the cyclodextrin cavity and the main structural features responsible for the enhancement of its solubility and photostability.

Acitretin↗
PubMed1994

Determination of acitretin in the skin, in the suction blister, and in plasma of human volunteers after multiple oral dosing.

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.(ABSTRACT TRUNCATED AT 250 WORDS)

Acitretin↗