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Figure 1.
Forehead Wrinkles of Patient 1 During Maximum Contraction at Baseline
Forehead Wrinkles of Patient 1 During Maximum Contraction at Baseline

The patient presented with severe forehead wrinkles (Wrinkle Severity Scale grade 3).

Figure 2.
Forehead Wrinkles of Patient 1 During Maximum Contraction 28 Days After the Injections
Forehead Wrinkles of Patient 1 During Maximum Contraction 28 Days After the Injections

Wrinkle Severity Scale grade 0 was achieved in the injected areas.

Figure 3.
Individual Variation in Patient 1 Response
Individual Variation in Patient 1 Response

Fields of anhidrotic effect 28 days after injection of 2 U of onabotulinumtoxinA on the right side of the forehead and 2 U of abobotulinumtoxinA on the left side of the forehead in patient 1. There was a larger area and diameter for onabotulinumtoxinA vs abobotulinumtoxinA.

Figure 4.
Individual Variation in Patient 17 Response
Individual Variation in Patient 17 Response

Fields of effect 28 days after injection of 2 U of onabotulinumtoxinA on the left side of the forehead and 2 U of abobotulinumtoxinA on the right side of the forehead. There was a larger area and diameter for onabotulinumtoxinA vs abobotulinumtoxinA and evidence of individual response.

Table 1.  
Horizontal and Vertical Diameters and Area of the Fields of Anhidrotic Effect at 28 Days at a Dose Equivalence of 1:1 OnabotulinumtoxinA to AbobotulinumtoxinA
Horizontal and Vertical Diameters and Area of the Fields of Anhidrotic Effect at 28 Days at a Dose Equivalence of 1:1 OnabotulinumtoxinA to AbobotulinumtoxinA
Table 2.  
Baseline and Postprocedure Evaluation With WSS and ECMAP Per Product
Baseline and Postprocedure Evaluation With WSS and ECMAP Per Product
1.
Pickett  A, Perrow  K.  Formulation composition of botulinum toxins in clinical use. J Drugs Dermatol. 2010;9(9):1085-1091.
PubMed
2.
Karsai  S, Raulin  C.  Do different formulations of botulinum toxin type A really have different migration characteristics? J Cosmet Dermatol. 2008;7(3):230. doi:10.1111/j.1473-2165.2008.00395.x.
PubMedArticle
3.
Hexsel  D, Brum  C, do Prado  DZ,  et al.  Field effect of two commercial preparations of botulinum toxin type A. J Am Acad Dermatol. 2012;67(2):226-232.
PubMedArticle
4.
Trindade de Almeida  AR, Marques  E, de Almeida  J, Cunha  T, Boraso  R.  Pilot study comparing the diffusion of two formulations of botulinum toxin type A in patients with forehead hyperhidrosis. Dermatol Surg. 2007;33(1, theme issue):S37-S43.
PubMedArticle
5.
Wohlfarth  K, Sycha  T, Ranoux  D, Naver  H, Caird  D.  Dose equivalence of two commercial preparations of botulinum neurotoxin type A. Curr Med Res Opin. 2009;25(7):1573-1584.
PubMedArticle
6.
Hexsel  DM, Soirefmann  M, Rodrigues  TC, do Prado  DZ.  Increasing the field effects of similar doses of Clostridium botulinum type A toxin–hemagglutinin complex in the treatment of compensatory hyperhidrosis. Arch Dermatol. 2009;145(7):837-840.
PubMedArticle
7.
Minor  V.  Ein Neues Verfahren zu der klinischen Untersuchung der Schweissabsonderung. Z Neurol. 1927;101:302-308.
8.
Hexsel  D, Rodrigues  TC, Soirefmann  M, Zechmeister-Prado  D.  Recommendations for performing and evaluating the results of the Minor test according to a sweating intensity visual scale. Dermatol Surg. 2010;36(1):120-122.
PubMedArticle
9.
Wohlfarth  K, Schwandt  I, Wegner  F,  et al.  Biological activity of two botulinum toxin type A complexes (Dysport and Botox) in volunteers. J Neurol. 2008;255(12):1932-1939.
PubMedArticle
10.
Hexsel  D, Dal’Forno  T, Hexsel  C, Do Prado  DZ, Lima  MM.  A randomized pilot study comparing the action halos of two commercial preparations of botulinum toxin type A. Dermatol Surg. 2008;34(1):52-59.
PubMedArticle
11.
Karsai  S, Raulin  C.  Current evidence on the unit equivalence of different botulinum neurotoxin A formulations and recommendations for clinical practice in dermatology. Dermatol Surg. 2009;35(1):1-8.
PubMedArticle
12.
Heckmann  M, Plewig  G; Hyperhidrosis Study Group.  Low-dose efficacy of botulinum toxin A for axillary hyperhidrosis: a randomized, side-by-side, open-label study. Arch Dermatol. 2005;141(10):1255-1259.
PubMedArticle
13.
Schnider  P, Moraru  E, Kittler  H, Voller  B, Kranz  G, Auff  E.  Botulinum toxin in the treatment of focal hyperhidrosis [in German]. Wien Klin Wochenschr. 2001;113(suppl 4):36-41.
PubMed
14.
Cliff  SH, Judodihardjo  H, Eltringham  E.  Different formulations of botulinum toxin type A have different migration characteristics. J Cosmet Dermatol. 2008;7(1):50-54.
PubMedArticle
15.
Happak  W, Liu  J, Burggasser  G, Flowers  A, Gruber  H, Freilinger  G.  Human facial muscles: dimensions, motor endplate distribution, and presence of muscle fibers with multiple motor endplates. Anat Rec. 1997;249(2):276-284.
PubMedArticle
16.
Ascher  B, Zakine  B, Kestemont  P, Baspeyras  M, Bougara  A, Santini  J.  A multicenter, randomized, double-blind, placebo-controlled study of efficacy and safety of 3 doses of botulinum toxin A in the treatment of glabellar lines. J Am Acad Dermatol. 2004;51(2):223-233.
PubMedArticle
17.
Monheit  G, Carruthers  A, Brandt  F, Rand  R.  A randomized, double-blind, placebo-controlled study of botulinum toxin type A for the treatment of glabellar lines: determination of optimal dose. Dermatol Surg. 2007;33(1, theme issue):S51-S59.
PubMedArticle
18.
Karsai  S, Adrian  R, Hammes  S, Thimm  J, Raulin  C.  A randomized double-blind study of the effect of Botox and Dysport/Reloxin on forehead wrinkles and electromyographic activity. Arch Dermatol. 2007;143(11):1447-1449.
PubMedArticle
19.
Karsai  S, Raulin  C.  Botox and Dysport: is there a dose conversion ratio in dermatology and aesthetic medicine? J Am Acad Dermatol. 2010;62(2):346-347.
PubMedArticle
Original Investigation
December 2013

Fields of Effects of 2 Commercial Preparations of Botulinum Toxin Type A at Equal Labeled Unit DosesA Double-blind Randomized Trial

Author Affiliations
  • 1Cosmetic Dermatology, Department of Dermatology, Pontificia Universidade Catolica do Rio Grande do Sul, Porto Alegre, Brazil
  • 2Brazilian Center for Studies in Dermatology, Porto Alegre, Brazil
  • 3Department of Neurology and Neurosurgery, Hospital Moinhos de Vento, Porto Alegre, Brazil
  • 4Internal Medicine Department, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil
JAMA Dermatol. 2013;149(12):1386-1391. doi:10.1001/jamadermatol.2013.6440
Abstract

Importance  This article provides new data on a controversial issue, the influence of doses on the diffusion characteristics of 2 botulinum toxins type A.

Objective  To assess the fields of effect of abobotulinumtoxinA and onabotulinumtoxinA at the same labeled unit dose (1:1 U) comparing sweat gland and muscle activity.

Design, Setting, and Participants  A prospective, single-center, randomized, double-blind study was conducted at the Brazilian Center for Studies in Dermatology in Porto Alegre, Brazil. The participants included 19 women.

Interventions  Each patient received 2 U of abobotulinumtoxinA on one side of the forehead and 2 U of onabotulinumtoxinA on the other side.

Main Outcomes and Measures  Horizontal and vertical diameter and area of the fields of anhidrotic effect, the amplitude of evoked compound muscle action potentials, and the 4-point validated Wrinkle Severity Scale were assessed at 28 days.

Results  The horizontal and vertical diameters of the fields of effect and the areas were significantly larger for onabotulinumtoxinA than those obtained for abobotulinumtoxinA. There were no significant differences between the products in the Wrinkle Severity Scale scores and Evoked Compound Muscle Action Potentials. OnabotulinumtoxinA had significantly more diffusion than abobotulinumtoxinA when isovolumetric injections of the same labeled unit dose of the products were injected.

Conclusions and Relevance  Although many studies state that diffusion is product dependent and abobotulinumtoxinA diffuses more than onabotulinumtoxinA, findings from the present study confirm that diffusion is dose dependent and the more potent dose tested diffuses more.

Trial Registration  clinicaltrials.gov Identifier: NCT01732809

Botulinum toxin type A has been extensively used for wrinkle correction with safe and effective results. The commercially available preparations of botulinum toxin type A result in similar clinical effects and are used for the same aesthetic indications, even though they are different formulations and have different potencies.1 Some physicians use only one brand; others use 2 or more different products in their clinical practices according to their experiences and preferences. The establishment of the best dose equivalence between the products is of great relevance in clinical practice, and this has been the subject of many discussions in publications and meetings.1,2 The fields of muscle and anhidrotic effect of botulinum toxin type A, also called by some authors "diffusion halos," are the best expression of the relevant clinical effects of the toxins. They can be objectively measured to identify product characteristics.

A recent study3 showed that abobotulinumtoxinA (Dysport; Ipsen) and onabotulinumtoxinA (Botox; Allergan) had similar fields of effect (FE [diffusion]) in muscles and sweat glands at a dose equivalence of 2.0:1.0 labeled units (abobotulinumtoxinA to onabotulinumtoxinA) and showed significantly greater diameters and areas of the fields of anhidrotic effect (FAE) for abobotulinumtoxinA compared with onabotulinumtoxinA at a dose equivalence of 2.5:1.0 labeled units (abobotulinumtoxinA to onabotulinumtoxinA). Even though these ratios showed significant differences in the sizes of the FAE, the FAE from the highest ratio was considered clinically irrelevant because it was less than 2 mm and the interindividual variations were more than 4 times greater.

Although some authors4 consider abobotulinumtoxinA as having greater diffusion than onabotulinumtoxinA, there are reports3,5 that both preparations have similar diffusion when equipotent doses are used. This implies that there are really no meaningful differences in the diffusion of the products; in fact, the only differences were the doses used in previous diffusion difference studies.

Other studies3,6 showed strong evidence that dose is the most important factor for botulinum toxin type A products because the FE (or diffusion) is dose dependent, and the usual volumes used in the reconstitution of the products (eg, 1-4 mL) are not important in the diffusion halos. From the patients’ perspective, other factors (eg, muscle mass, area of the injections, intensity of the sweating, and individual characteristics, perhaps related to the number of neuromuscular junctions and level of acetylcholine discharge to be blocked) can affect the size of the FE or diffusion halos. The aim of the present study was to assess the FE/diffusion characteristics of abobotulinumtoxinA and onabotulinumtoxinA at the same dose (1:1 labeled unit equivalence) regarding muscle and sweat gland activities.

Methods
Study Design and Participants

This was a prospective, single-center, randomized, double-blind study. All participants were recruited from a research center in Porto Alegre, Brazil, and provided written informed consent. This study was approved by the local ethics committee of Associação Hospitalar Moinhos de Vento, and all Good Clinical Practice standards, Declaration of Helsinki protocols, and national regulations were maintained. The main inclusion criteria were women aged 18 to 60 years, presence of moderate to severe forehead wrinkles on both sides at the maximum contraction of the frontalis muscle according to the Wrinkle Severity Scale3 (WSS), positive sweating according to the Minor Test,7 and scores from III to V on the Sweat Intensity Visual Scale.8

Assessments

Three evaluations were performed: baseline, visit 1 (injection), and visit 2 (28 days after the procedure). Clinical assessments included the 4-point validated scale for forehead (WSS) at rest and at maximum frontalis activity. Photographic assessments also were performed at baseline and at 28 days and evaluated by one independent investigator to determine a WSS. Adverse events were recorded after treatment at visits 1 and 2.

The amplitude of the evoked compound muscle action potentials9 (ECMAP) in the frontalis muscle on stimulation of the facial nerve was performed at baseline and visit 2 using surface electrodes on the forehead and electrical stimulation of the facial nerve according to standard neurophysiologic procedures. The amplitude of the ECMAP was performed by an experienced neurologist (F.T.R.) using an electromyography device (Teca Sapphire; Teca Corp). Photographic assessments included a standard set of 3 photographs of the forehead muscles: at rest and at maximum activity of the frontalis muscle and when the Minor test was performed. The horizontal and vertical diameters of the FAE were quantified using commercial software (Mirror-DPS 7.02; Canfield Scientific Inc) and are expressed in centimeters. The area of the FAE was calculated using the same software and was performed considering the perimeter of the FAEs, assuming that they were not perfect circles.

The products were reconstituted using 0.9% sterile saline solution without preservative 5-20 minutes before administration. To obtain isovolumetric injections at a dose equivalence of 1:1 labeled units, products were reconstituted in the following manner. AbobotulinumtoxinA, 500 U per vial, was diluted in 2.5 mL, and 1 U was aspirated into each syringe. This dilution resulted in a concentration of 200 U/mL (2 U/0.01 mL) of the reconstituted product. The same volume (0.01 mL) of saline solution was then added to each syringe, resulting in a concentration of 2 U/0.02 mL. OnabotulinumtoxinA, 100 U per vial, was reconstituted with 1 mL of 0.9% saline, resulting in a concentration of 100 U/mL (2 U/0.02 mL) of the reconstituted product.

The injections were administered by a dermatologist (C.H.) experienced in the use of botulinum toxin type A at one point on each side of the forehead. The points were marked using a template created from a sheet of x-ray film to ensure that the location of the injection points was marked consistently from patient to patient. Standard isovolumetric injections (0.02 mL of each product) were administered using 0.3-mL syringes with a 29-gauge short needle, 0.5 cm in length (Ultra-Fine II; Becton Dickinson and Company), with the template positioned on the patient’s forehead. Caps of the needles were cut to ensure that the products were injected at a standardized depth of 3 mm.

Patients were randomized to the side of the forehead (left or right) in which the products were administered. The randomization list was generated by a statistician, and commercial software was used (SPSS, version 16.0; SPSS Inc). Blinding was maintained for patients and investigators using identical syringes for the injections. These were identified by a code known only by the pharmacist (J.S.S.) in charge of the dilution of the products. During the study, the randomization list was kept in a sealed envelope.

Patients were sequentially assigned to 1 of 2 groups to receive isovolumetric (0.02 mL) doses of 2 U of abobotulinumtoxinA injected on one side of the forehead and 2 U of onabotulinumtoxinA injected on the contralateral side. Group A patients received 2 U/0.02 mL of reconstituted abobotulinumtoxinA on the right side of the forehead and 2 U/0.02 mL of reconstituted onabotulinumtoxinA on the left side. Group B patients received 2 U/0.02 mL of reconstituted abobotulinumtoxinA on the left side of the forehead and 2 U/0.02 mL of reconstituted onabotulinumtoxinA on the right side.

Statistical Analysis

Considering the results of a previous study,3 which found a difference of 0.30 cm for the horizontal diameter and of 0.58 cm2 for the area of the FAE, and defining a power of 80% and an α error of 5%, a sample size of 16 was obtained. However, 19 individuals were enrolled because a dropout rate of 15% was considered.

Paired and unpaired t tests were used for analysis of continuous variables, and the χ2 test was used for categorical variables. Other data are expressed as mean (SD), median (range), or percentage. The α error was considered to be significant at P < .05. Commercial software (SSPS, version 16.0) was used to analyze the data.

Results

Nineteen women were enrolled in this study between July 29, 2011, and October 14, 2011, and the last participant completed the study on November 11, 2011. There was 1 dropout, resulting in 18 patients completing the study. Mean age was 38.4 (10.2) years (range, 28-55 years), and all patients were white and reported no use of illicit drugs. The Fitzpatrick classification of 4 participants (22%) was II, 13 participants (72%) were Fitzpatrick III, and 1 participant (6%) was Fitzpatrick IV. Five women (28%) were currently smoking.

Horizontal and vertical diameters and the area of the FAE were significantly larger for onabotulinumtoxinA than were those obtained for abobotulinumtoxinA 28 days after the procedure (P < .001) at the labeled doses used (Table 1).

Table 2 reports the results for WSS and ECMAP at baseline and at 28 days for the 2 treatments. There were no statistically significant differences between the proportions of participants regarding WSS grading, both at rest and during maximum contraction, at baseline and at 28 days after the onabotulinumtoxinA or abobotulinumtoxinA injections, assessed at the visit and by photographs. In general, participants achieved reduction in wrinkles with the injected doses for both treatments (Figure 1 at baseline and Figure 2 after 28 days). After 28 days, patients had lower WSS scores.

Both onabotulinumtoxinA and abobotulinumtoxinA significantly reduced ECMAP values at visit 2 when compared with baseline: 1079.11 (266.02) vs 165.39 (232.10) μV (P < .001) and 1108.17 (364.76) vs 202.89 (258.44) μV (P < .001). However, ECMAP values were not significantly different between the products.

Adverse events were related to injection technique and were mild and transitory. One participant (6%) presented with erythema at the injection sites (both sides) and 3 participants (17%) had minimal bleeding at the injection sites immediately after administration, all on the left side, with no significant differences between the products (2 on the abotulinumtoxinA-injected side and 1 on the onabotulinumtoxinA-injected side). One patient reported meniscus rupture, which hampered her from performing the Minor test, and data from this patient were excluded from the evaluation. This event was not related to the study procedures. There were no serious adverse events.

Discussion

This noncommercially sponsored study evaluated FAEs of 2 commercial preparations of botulinum toxin type A at an equivalence dose of 1:1 labeled units administered into the forehead. The FAEs of the tested products were evaluated by measuring the horizontal and vertical anhidrotic zone diameters, as well as the area surrounding the injection points, using the Minor test. The resultant zones were later analyzed using commercial software. The muscle activity in the injected areas was evaluated using the validated 4-point WSS3 and ECMAP9 by electromyography.

Treatment with both products resulted in wrinkle improvement as assessed by the WSS and decrease in muscle activity by the ECMAP. No significant difference between the 2 products was observed when considering these 2 distinct end points and methods of measurement. However, FAEs evaluated using the Minor test at the 28-day follow-up were significantly larger for onabotulinumtoxinA than those obtained with abobotulinumtoxinA.

Dose equivalences from 6:1 to 1:1 U (abobotulinumtoxinA to onabotulinumtoxinA) have been described.10,11 In the past few years, many authors3,12,13 suggested the dose equivalence between the products to be used in clinical practice is approximately 2.5:1.0 U (abobotulinumtoxinA to onabotulinumtoxinA) or even 2.0:1.0 U (abobotulinumtoxinA to onabotulinumtoxinA) as stated in many articles and supported by Dr D Hexsel. The dose equivalence of 1:1 labeled units is not recommended for clinical practice; nevertheless, the proposal for the present study was to examine treatment with equal labeled units to attempt to better explain each product’s characteristics regarding potency and FAE characteristics.

It has been demonstrated by different studies2,4,14 that a higher diffusion or larger FAE of abobotulinumtoxinA occurs when using high equivalent doses, such as 3:1 labeled units (abobotulinumtoxinA to onabotulinumtoxinA) or more. One study3 showed larger FE with 2.5:1 labeled unit equivalence and supports the equipotent and equivalent dose of these products at approximately 2:1 (abobotulinumtoxinA to onabotulinumtoxinA). Another study9 showed the apparent real equivalence between abobotulinumtoxinA and onabotulinumtoxinA as 1.57:1 labeled units (abobotulinumtoxinA to onabotulinumtoxinA), but this result was extrapolated from a dose-ranging study on the extensor digitorum brevis muscle in each foot of volunteers. Facial muscles are distinctly different from other muscles in the body because they contain more than 1 neuromuscular junction per muscle fiber,15 and this must be taken into account when comparing data from different studies, especially facial muscle results vs results from other muscles. Overall, these studies support the fact that higher doses of botulinum toxin type A are more efficient in producing greater FAE and fields of muscle effect with the commercial preparations.3,9

Isovolumetric injections of the same number of labeled units of abobotulinumtoxinA and onabotulinumtoxinA showed smaller FAE (less diffusion) in the abobotulinumtoxinA injection sites compared with onabotulinumtoxinA, suggesting that the size of the FAE or diffusion halos can be altered according to the dose used and the tested dose equivalence. However, abobotulinumtoxinA demonstrated the same directly measured effects on muscle activity as onabotulinumtoxinA, with no statistically significant differences between the WSS and ECMAP results observed. Similar effects on wrinkles and ECMAP produced by both products at the same labeled unit dose is an interesting finding, even when interpreted in the context of this short-term (28 days) study. Because the effects themselves and their duration are also believed to be dose dependent, further studies using lower doses for cosmetic purposes are needed to provide more data on the duration of effect of lower doses of botulinum toxin type A products. However, studies16,17 have clearly demonstrated that the duration of effect is also dose dependent.

In previous studies, differences larger than 0.30 cm for the horizontal diameter and 0.58 cm2 for the area of the FAE were considered clinically relevant.3,10 In the present trial, the differences found between the 2 studied products at 28 days were 0.40 cm for the horizontal diameter and approximately 0.63 cm2 for the area of the FAE (Figure 3 and Figure 4). Nevertheless, this should be more extensively studied to better understand the relevant aspects in aesthetic uses (mainly muscular effects) and among the different products, as well as the individual responses to the same labeled doses, which may affect the results in clinical practice.

Considering that no significant difference between abobotulinumtoxinA and onabotulinumtoxinA was found for wrinkles with the 2:1 dose equivalence used previously for ECMAP and FAE and that with the 2.5:1 dose equivalence a higher diameter, ECMAP, and FAE were found for abobotulinumtoxinA,3 this study supports the observation of Karsai and colleagues18,19 that the size of the FAE is simply a dose effect as opposed to the claims that one product diffuses more than the other.

In conclusion, onabotulinumtoxinA has significantly larger FAE than abobotulinumtoxinA when isovolumetric injections of the same labeled unit doses of the products were injected, supporting the theory that the FAE is mainly related to the dose used in clinical practice and equivalent ratios in clinical trials. Both products had similar results for cosmetic use and muscular effect after 28 days. The results of this study open new horizons for the use of smaller doses of toxins for cosmetic purposes. Longer studies are needed to examine this approach.

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Article Information

Accepted for Publication: June 27, 2013.

Corresponding Author: Doris Hexsel, MD, Brazilian Center for Studies in Dermatology, 782 Dr. Timoteo St, ground floor, 90570-040, Porto Alegre, RS, Brazil (doris@hexsel.com.br).

Published Online: October 9, 2013. doi:10.1001/jamadermatol.2013.6440.

Author Contributions: Drs D. Hexsel and C. Hexsel had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Study concept and design: D. Hexsel.

Acquisition of data: All authors.

Analysis and interpretation of data: D. Hexsel, Siega, Rotta, Rodrigues.

Drafting of the manuscript: D. Hexsel, Siega, Schilling-Souza, Rodrigues.

Critical revision of the manuscript for important intellectual content: All authors.

Statistical analysis: Siega, Rodrigues.

Administrative, technical, and material support: D. Hexsel, C. Hexsel, Rotta, Rodrigues.

Study supervision: D. Hexsel, Siega, Schilling-Souza, Rodrigues.

Conflict of Interest Disclosures: Dr D Hexsel has received research funding from L’Óreal, Cynosure, Syneron, Ipsen, Allergan, Galderma, and Medicis; has served as a consultant for Ipsen and Galderma; and has been a member of the speakers bureaus for Ipsen and Galderma. No other disclosures were reported.

Funding/Support: This study was supported by the Brazilian Center for Studies in Dermatology, a nonprofit organization.

Role of the Sponsors: This was a nonsponsored study. The Brazilian Center for Studies in Dermatology designed and conducted the study; collected, analyzed, and interpreted the data; and prepared, reviewed, and approved the manuscript

Additional Contributions: Andy Pickett, PhD, provided critical commentaries on this article, for which he received no financial compensation. Diana Monti Atik, BPharm, an employee of the research center during the trial, assisted with acquisition of the data and received her usual salary support.

References
1.
Pickett  A, Perrow  K.  Formulation composition of botulinum toxins in clinical use. J Drugs Dermatol. 2010;9(9):1085-1091.
PubMed
2.
Karsai  S, Raulin  C.  Do different formulations of botulinum toxin type A really have different migration characteristics? J Cosmet Dermatol. 2008;7(3):230. doi:10.1111/j.1473-2165.2008.00395.x.
PubMedArticle
3.
Hexsel  D, Brum  C, do Prado  DZ,  et al.  Field effect of two commercial preparations of botulinum toxin type A. J Am Acad Dermatol. 2012;67(2):226-232.
PubMedArticle
4.
Trindade de Almeida  AR, Marques  E, de Almeida  J, Cunha  T, Boraso  R.  Pilot study comparing the diffusion of two formulations of botulinum toxin type A in patients with forehead hyperhidrosis. Dermatol Surg. 2007;33(1, theme issue):S37-S43.
PubMedArticle
5.
Wohlfarth  K, Sycha  T, Ranoux  D, Naver  H, Caird  D.  Dose equivalence of two commercial preparations of botulinum neurotoxin type A. Curr Med Res Opin. 2009;25(7):1573-1584.
PubMedArticle
6.
Hexsel  DM, Soirefmann  M, Rodrigues  TC, do Prado  DZ.  Increasing the field effects of similar doses of Clostridium botulinum type A toxin–hemagglutinin complex in the treatment of compensatory hyperhidrosis. Arch Dermatol. 2009;145(7):837-840.
PubMedArticle
7.
Minor  V.  Ein Neues Verfahren zu der klinischen Untersuchung der Schweissabsonderung. Z Neurol. 1927;101:302-308.
8.
Hexsel  D, Rodrigues  TC, Soirefmann  M, Zechmeister-Prado  D.  Recommendations for performing and evaluating the results of the Minor test according to a sweating intensity visual scale. Dermatol Surg. 2010;36(1):120-122.
PubMedArticle
9.
Wohlfarth  K, Schwandt  I, Wegner  F,  et al.  Biological activity of two botulinum toxin type A complexes (Dysport and Botox) in volunteers. J Neurol. 2008;255(12):1932-1939.
PubMedArticle
10.
Hexsel  D, Dal’Forno  T, Hexsel  C, Do Prado  DZ, Lima  MM.  A randomized pilot study comparing the action halos of two commercial preparations of botulinum toxin type A. Dermatol Surg. 2008;34(1):52-59.
PubMedArticle
11.
Karsai  S, Raulin  C.  Current evidence on the unit equivalence of different botulinum neurotoxin A formulations and recommendations for clinical practice in dermatology. Dermatol Surg. 2009;35(1):1-8.
PubMedArticle
12.
Heckmann  M, Plewig  G; Hyperhidrosis Study Group.  Low-dose efficacy of botulinum toxin A for axillary hyperhidrosis: a randomized, side-by-side, open-label study. Arch Dermatol. 2005;141(10):1255-1259.
PubMedArticle
13.
Schnider  P, Moraru  E, Kittler  H, Voller  B, Kranz  G, Auff  E.  Botulinum toxin in the treatment of focal hyperhidrosis [in German]. Wien Klin Wochenschr. 2001;113(suppl 4):36-41.
PubMed
14.
Cliff  SH, Judodihardjo  H, Eltringham  E.  Different formulations of botulinum toxin type A have different migration characteristics. J Cosmet Dermatol. 2008;7(1):50-54.
PubMedArticle
15.
Happak  W, Liu  J, Burggasser  G, Flowers  A, Gruber  H, Freilinger  G.  Human facial muscles: dimensions, motor endplate distribution, and presence of muscle fibers with multiple motor endplates. Anat Rec. 1997;249(2):276-284.
PubMedArticle
16.
Ascher  B, Zakine  B, Kestemont  P, Baspeyras  M, Bougara  A, Santini  J.  A multicenter, randomized, double-blind, placebo-controlled study of efficacy and safety of 3 doses of botulinum toxin A in the treatment of glabellar lines. J Am Acad Dermatol. 2004;51(2):223-233.
PubMedArticle
17.
Monheit  G, Carruthers  A, Brandt  F, Rand  R.  A randomized, double-blind, placebo-controlled study of botulinum toxin type A for the treatment of glabellar lines: determination of optimal dose. Dermatol Surg. 2007;33(1, theme issue):S51-S59.
PubMedArticle
18.
Karsai  S, Adrian  R, Hammes  S, Thimm  J, Raulin  C.  A randomized double-blind study of the effect of Botox and Dysport/Reloxin on forehead wrinkles and electromyographic activity. Arch Dermatol. 2007;143(11):1447-1449.
PubMedArticle
19.
Karsai  S, Raulin  C.  Botox and Dysport: is there a dose conversion ratio in dermatology and aesthetic medicine? J Am Acad Dermatol. 2010;62(2):346-347.
PubMedArticle
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