title: Botulinum toxin therapy: reduction of injection site pain by pH normalisation.
abstract: Botulinum toxin (BT) is injected intramuscularily and may produce injection site pain (ISP). We wanted to explore whether the pH value of the reconstituted BT drug contributes to ISP and, if so, what strategies can be applied to reduce it. In part 1 of the study, pH values of different reconstitution solutions and of major BT drugs reconstituted with different reconstitution solutions were assessed. In part 2, the effects of reconstitution with normal saline (NS) and Ringer acetate (RA) were compared intraindividually and in a double blind fashion in 34 patients with blepharospasm. pH values of reconstitution solutions were 5.52 ± 0.02 for NS, 6.98 for RA, 6.31 for Ringer lactate, 6.56 for electrolyte and 5.31 for bacteriostatic solution. pH values for NS-reconstitution were 6.09 ± 0.20 for Botox(®), 5.95 ± 0.24 for Dysport(®) and 5.81 ± 0.18 for Xeomin(®). pH values for RA-reconstitution were 6.95 ± 0.03 for Botox(®), 7.01 ± 0.02 for Dysport(®) and 6.87 ± 0.06 for Xeomin(®). By using RA instead of NS the pH could be increased by 0.86 for Botox(®), by 1.06 for Dysport(®) and by 1.06 for Xeomin(®). 47 % of the patients experienced less ISP when Botox(®)-RA was given rather than Botox(®)-NS, 76 % when Xeomin(®)-RA was given rather than Xeomin(®)-NS. None of the patients reported a difference in efficacy between NS- and RA-reconstitution. Despite previous reports, reconstituted BT type A drugs show acidic pH values. Normalising these pH values by use of RA instead of NS reduces ISP considerably without sacrificing clincial efficacy.
authors.affiliation: Movement Disorders Section, Department of Neurology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625, Hannover, Germany. dressler.dirk@mh-hannover.de.
authors.forename: Dirk
authors.initials: D
authors.lastname: Dressler
authors.affiliation: Movement Disorders Section, Department of Neurology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625, Hannover, Germany.
authors.forename: Fereshte
authors.initials: F
authors.lastname: Adib Saberi
authors.affiliation: Movement Disorders Section, Department of Neurology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625, Hannover, Germany.|Institute of Toxicology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625, Hannover, Germany.
authors.forename: Hans
authors.initials: H
authors.lastname: Bigalke
mesh_terms: D000368:Aged; D001764:Blepharospasm / Q000188:drug therapy; D001905:Botulinum Toxins / Q000737:chemistry* / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004339:Drug Compounding; D005260:Female; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008297:Male; D008875:Middle Aged; D009465:Neuromuscular Agents / Q000737:chemistry / Q000627:therapeutic use*; D010146:Pain / Q000188:drug therapy* / Q000209:etiology; D013997:Time Factors
chemical_list: D009465:Neuromuscular Agents; D001905:Botulinum Toxins
keywords: Botulinum toxin; Normal saline; Reconstitution solution; Ringer acetate; Therapeutic use; pH value