Effect of volume and concentration on the diffusion of botulinum exotoxin A

Objective: To investigate whether the volume of solution used to inject equivalent units of botulinum exotoxin A affects the diffusion of toxin and areas of rhytid diminution in the treatment of dynamic forehead lines. Design: Ten volunteers with dynamic forehead lines were included. Each study patient received a single injection at a point 2.5 cm above the orbital rim on either side of the forehead with equivalent units, but in different volumes, of botulinum exotoxin A. The sides of injection were randomized; one side of the patient's forehead was injected first with 5 U of botulinum exotoxin A in 0.25 mL (2 U/0.1 mL) of preserved saline in the midpupillary line, followed by injection of the other side with 5 U in 0.05 mL of preserved saline (2 U/0.02 mL). There was a 5-fold difference in volume injected. Subjects were evaluated 14 days later for total area affected during visual inspection of the subjects' foreheads during active muscle contraction. Setting: Private dermatology office. Main Outcome Measure: Visual inspection to measure the area of rhytid effacement in both height and width. Results: The area affected by the botulinum exotoxin A injection was 50% greater in the side with the larger volume in 9 of 10 subjects. The average area affected was 6.05 cm(2) for the injection of the larger volume compared with 4.12 cm(2) for the injection with the smaller volume. The shape of rhytid effacement was oval, rather than round, with the average width longer than the average height. Conclusions: In this prospective, randomized, controlled study, we found that injection of botulinum exotoxin A in low concentration and higher volume resulted in greater diffusion and a larger affected area. The pattern of toxin spread is altered by muscular contraction in the injected sites. These results show that the dilution has implications on the desired effect of botulinum exotoxin A.