Clinical pharmacokinetics profile of ivermectin 1% cream after dermal applications on the face

AIM: To investigate the pharmacokinetics profile of Ivermectin 1% cream after topical treatment in patients with papulopustular rosacea(PPR).METHODS: Ivermectin 1% cream is a new, effective, and safe treatment for PPR. The human pharmacokinetic(PK) profile of ivermectin and its circulating metabolites were assessed following topical application of ivermectin 1% cream to the face. Clinical PK assessments were conducted after 4 wk of treatment using healthy volunteers and PPR subjects. Additionally, PK sampling was conducted up to 1 year of treatment in clinical phase 3 studies. Plasma concentrations of ivermectin and ivermectin metabolites were determined using high-performance liquid chromatography with fluorescence detection after a specific derivation to increase sensitivity.RESULTS: Systemic exposure to ivermectin was quantifiable at low levels in healthy and moderate to severe PPR subjects following the first topical application of ivermectin 1% cream(mean Cmax of 0.5 ± 0.2 ng/mL and 0.7 ± 0.5 ng/mL in healthy volunteers and PPR subjects, respectively). Ivermectin plasma levels reached a plateau after 2 wk of repeated topical application, indicating that steady-state concentrations had been reached. No further ivermectin plasma accumulation was observed during the long-term clinical studies that investigated ivermectin treatment up to 1 year. Investigation of ivermectin metabolites indicated that 2 circulating metabolites represented more than 10% of parent drug systemic exposure at steady state. Repeated topical application of ivermectin 1% cream resulted in lower systemic exposure levels when compared with orally administered ivermectin, suggesting limited transdermal absorption of ivermectin. Topically applied ivermectin is cleared from the plasma slowly(with a prolonged plasma half-life when compared to the oral route).CONCLUSION: Applications of ivermectin 1% cream result in low systemic exposure levels. Steady–state conditions are achieved by 2 wk without further accumulation under chronic treatment.

Evaluation of Rheometry Amplitude Sweep Cross-Over Point as an Index of Flexibility for HA Fillers

Background: The majority of studies published on rheology of hyaluronic acid (HA) fillers have focused on results from frequency sweeps within the linear viscoelastic region (LVR), i.e. at nearly static conditions. To study the properties and behavior of HA fillers at more dynamic conditions, it is necessary to go outside the LVR. Objective: Evaluation of the G’/G’’ cross-over point from the amplitude sweep is suggested as a manner to estimate the flexibility of HA fillers. Materials and methods: Rheological properties of 7 HA fillers were measured in an amplitude sweep from 0.1% to 10000% strain at 1 Hz, using an Anton Paar MCR 301, a PP-25 measuring system with a gap of 1 mm at 25℃ and a 30-min relaxation time. The cross-over point was evaluated for stress, strain and G (G’ and G’’ identical), the values denoted xStrain, xStress and xG. Results: The xStrain values spanned from below 1000% to above 2000% for the products based on the Optimal Balance Technology (OBT)? (in the US, XpresHAn Technology?), compared to below 100% for the products based on the NASHA? technology. Conclusions: Measurement of the flexibility provides a more complete picture of the rheological properties of HA fillers as a complement to firmness measured as G’. The test results show that the Restylane family of products covers a large range in flexibility, and that the flexibility can be estimated using xStrain derived from the amplitude sweep.

欧洲银屑病患者现状的调查

Background: Most of the psoriasis that affects the European population is treated with topical preparations. Compliance rates, however, are known to be quite low. Objective: To provide an update on how psoriasis is experienced by patients and how well these patients comply with prescribed topical treatment. Methods: This was an observational and transversal survey conducted in 1281 patients with psoriasis. Patient input alone formed the basis of the study. Participants were contacted through the national psoriasis patient associations in France, the United Kingdom, Belgium, Germany and the Netherlands. Results: The study showed that 32% of the patients suffer currently from psoriasis in the face, skin folds and genital areas-areas very sensitive to topical treatments. Most of the patients (74% ) considered their psoriasis as at least moderately severe, and 73% stated not to comply with their current treatment. Lack of efficacy and messiness of the treatment were the main reasons for non-compliance, an element that is especially important for the use in sensitive areas such as the face, skin folds and genitalia. Conclusion: The present survey confirmed that cosmetic acceptability is, together with efficacy and safety, a very important aspect of a successful treatment of psoriasis.

0.3%阿达帕林凝胶治疗寻常痤疮:一项多中心、随机、双盲,对照Ⅲ期试验

Background: A new 0.3% gel formulation of adapalene has been developed. Objective: We sought to provide evidence of the superiority of adapalene gel 0.3% over adapalene gel 0.1% and gel vehicle in the treatment of acne. Methods: A total of 653 patients were randomized to receive adapalene gel 0.3% , adapalene gel 0.1% , or vehicle once daily for 12 weeks (2:2:1 randomization). Analysis for efficacy was conducted on correlated repeated measurements at weeks 8 and 12 using Generalized Estimating Equation methodology. Results: Adapalene gel 0.3% was significantly superior to adapalene gel 0.1% and vehicle in success rate, total lesion count, and inflammatory lesion count. A consistent, dose- dependent effect was demonstrated for all efficacy measures. Signs and symptoms were mostly mild to moderate and transient in nature. Limitations: Adjunctive topical or oral agents and their impact on acne were not studied in this trial. Conclusions: Adapalene gel 0.3% was effective and well tolerated in the treatment of acne.