Assessment of Clonidine Orally Disintegrating Tablet for Pre-anesthetic Medication in Pediatric Surgery

Abstract

Clonidine hydrochloride (CL), an a 2 -adrenoceptor agonist, is currently used for pre-anesthetic medication owing to its sedative and analgesic properties.1-3) These unique properties provide pre-operative sedation and preventing post-operative pain and vomiting in pediatric patients, as well as adults. [4][5][6][7] One drawback for this medicine applying to pediatric patients is difficulty in taking. To overcome this problem, several formulations including lollipop have been developed so far. [8][9][10] We previously evaluated efficacy and safety of lollipop preparation in pediatric patients and found individual variation of sedative effects owing to variable blood CL concentrations, which were due to the difference in taking lollipop in individual patient.9) The patients especially aged 1-3 years old seemed to be difficult to lick the CL-lollipop completely, so they could not take it up to the prescribed dose. We, therefore, developed orally-disintegrating (OD) tablets as an alternative preparation of CL to resolve the problem. 11)In this study, we evaluated the newly developed OD preparation by comparing with lollipop preparation in sedation score, blood CL concentration and hemodynamic changes in pediatric surgery. SUBJECTS AND METHODS SubjectsWe studied 23 pediatric patients, American Society of Anesthesiologists' (ASA) physical status I, ranging in age from 1 to 11 years. General anesthesia for elective surgery was performed for each patient. The study protocol was approved by our Clinical Investigation Committee, and informed consent was obtained from the parents or their guardians. CL-preparation, OD or lollipop (4 mg/kg), was administered 90 min before entering the operating room. Anesthesia was induced with 5% sevoflurane in 6 l/min oxygen for 10 min. Patient characteristics were summarized in Table 1.There was no difference in patient's backgrounds between OD and lollipop group.Preparation of CL Preparations CL-OD and -lollipop were prepared in our hospital according to the method previously described. 8,9,11) CL was obtained from Wako Pure Chemical Industries (Osaka, Japan). CL-OD was prepared by the method of drying an aqueous CL suspension. 11) Briefly, using CL and powdered lactose (Yoshida Pharmaceutical, Tokyo, Japan), composition ratio of CL suspension was 2 : 1 (powdered lactose: 0.048% or 0.072% CL-solution). Four milliliters of CL solution and 8 g powdered lactose was mixed for 60 s. Two hundred fifty milligrams of CL-suspension was put into the mold, and dried inside of refrigerator at 4°C and at 72% humidity for 4 d. Dried formulation (0.167 The purpose of this study is to assess orally-disintegrating (OD) tablet of clonidine hydrochloride (CL) for a pre-operative sedation in pediatric surgery. Sedation score and plasma CL concentration of OD formulation was compared with original preparation, CL lollipop, in pediatric patients. Fourteen patients (age: 3.9؎2.3 years, weight: 16.9؎5.0 kg) for OD group and 9 patients (age: 4.4؎3.1 years, weight: 17.2؎7.0 kg) for lollipop group received 4 m m...

Oral bioavailability of clonidine in children

“…High bioavailability (75–100%) has been described after oral administration in adults (9,10). Although the type of oral formulation may influence observed concentrations (11), no pediatric data regarding oral bioavailability have been published. Despite the lack of pediatric data, the bioavailability described in adults has been extrapolated to the pediatric population.…”

A mini-review of non-parenteral clonidine preparations for paediatric sedation

“…In addition, the time taken to consume a lollipop could be variable between patients. A further study found that orally disintegrating tablet formulations were superior to lollipops in reaching satisfactory sedation . A summary of oral transmucosal formulations identified in the literature search are presented in Table .…”

“…Lollipop formulations identified in this literature search were sweetened with sucrose and starch syrup, but excipients used to improve the palatability of the ODTs and sublingual tablets were not described . No study provided data on taste acceptability from patients.…”

“…Clonidine lollipops have been investigated for their potential as pre-anaesthetic medication. [36,37] One study found that satisfactory sedation was achieved in ten of 16 patients but that patients aged 1-3 years were unable to consume a sufficient dose for adequate sedation. [36] In addition, the time taken to consume a lollipop could be variable between patients.…”

“…[38] Lollipop formulations identified in this literature search were sweetened with sucrose and starch syrup, but excipients used to improve the palatability of the ODTs and sublingual tablets were not described. [36,37] No study provided data on taste acceptability from patients. In addition, studies involved children over the age of 12 months and the sample sizes in each study were small (Table 3).…”