Pharmacokinetic drug interaction between atorvastatin and ezetimibe in healthy Korean volunteers

Atorvastatin and ezetimibe are frequently co-administered to treat patients with dyslipidemia for the purpose of low-density lipoprotein cholesterol control. However, pharmacokinetic (PK) drug interaction between atorvastatin and ezetimibe has not been evaluated in Korean population. The aim of this study was to investigate PK drug interaction between two drugs in healthy Korean volunteers. An open-label, randomized, multiple-dose, three-treatment, three-period, Williams design crossover study was conducted in 36 healthy male subjects. During each period, the subjects received one of the following three treatments for seven days: atorvastatin 40 mg, ezetimibe 10 mg, or a combination of both. Blood samples were collected up to 96 h after dosing, and PK parameters of atorvastatin, 2-hydroxyatorvastatin, total ezetimibe (free ezetimibe + ezetimibe-glucuronide), and free ezetimibe were estimated by non-compartmental analysis in 32 subjects who completed the study. Geometric mean ratios (GMRs) with 90% confidence intervals (CIs) of the maximum plasma concentration (C(max,ss)) and the area under the curve within a dosing interval at steady state (AUC(τ,ss)) of atorvastatin when administered with and without ezetimibe were 1.1087 (0.9799–1.2544) and 1.1154 (1.0079–1.2344), respectively. The corresponding values for total ezetimibe were 1.0005 (0.9227–1.0849) and 1.0176 (0.9465–1.0941). There was no clinically significant change in safety assessment related to either atorvastatin or ezetimibe. Co-administration of atorvastatin and ezetimibe showed similar PK and safety profile compared with each drug alone. The PK interaction between two drugs was not clinically significant in healthy Korean volunteers.

Correction of Maxillary Arch of Cleft Lip and Palate Patient using Active Stabilized Extraoral Apparatus

Presurgical maxillary orthodontics during neonatal period has been advocated to facilitate cleft lip and/or palate cases through correcting widened alveolar bone and twisting or bending protruded premaxilla. This may improve post-orthodontic surgical lip repair procedure. Premaxilla cannot be moved into the correct position by a passive acrylic appliance alone. Therefore active acrylic appliance may be necessary and force vector, amount and stability of appliance are mandatory. Because neonatal infant still doesn't have a fully grown face, there may be some limitations to apply proper active force to the patient. The authors devised a new active stabilized extraoral appliance which provided stable extraoral force in the cleft lip and/or palate patients. We applied our new device to 2 infants with unilateral and bilateral cleft lip and palate. Stability of extraoral part has been increased by elastic rubber band, and the intraoral part is firmly connected to extraoral part. By using this device, the gap has decreased from 11.5mm to 6.5mm between right and left alveolar ridge in 1-month infant with unilateral case after 7 weeks. In 2-month infant with bilateral cleft, the length between premaxilla and alveolar ridge decreased from 6.5mm to 2.0mm after 4 weeks. We think our intraoral active stabilized orthodontic appliance could be widly used in cleft patients to put their maxillary segments to desirable position. This procedure makes the cleft lip surgery easier, with less tension.