Jarun Sayasathid

Bioequivalence of Generic Lamotrigine 100-mg Tablets in Healthy Thai Male Volunteers: A Randomized, Single-Dose, Two-Period, Two-Sequence Crossover Study

BACKGROUND Lamotrigine is an antiepileptic drug which has been used in the treatment of epilepsy and bipolar disorder. A search of the literature did not find previously published bioequivalence and pharmacokinetic evaluations of lamotrigine in healthy Thai male volunteers. OBJECTIVE The aim of this study was to compare the pharmacokinetic parameters between 2 brands of lamotrigine in healthy Thai male volunteers. METHODS A randomized, single-dose, 2-period, 2-sequence, crossover study design with a 2-week washout period was conducted in healthy Thai males. Subjects were randomized to receive either the test or reference formulation in the first period. All subjects were required to be nonsmokers and without a history of alcohol or drug abuse. Plasma samples were collected over a 120-hour period after 100-mg lamotrigine administration in each period. A validated high-performance liquid chromatography ultraviolet method was used to analyze lamotrigine concentration in plasma. Pharmacokinetic parameters were determined using a noncompartmental method. Bioequivalence between the test and reference products, as defined by the US Food and Drug Administration (FDA), is determined when the ratio for the 90% CIs of the difference in the means of the log-transformed AUC(0-t), AUC(0-infinity), and C(max) of the 2 products are within 0.80 and 1.25. Adverse events were determined by measuring vital signs after dosing. Subjects were also asked if they suffered from undesirable effects such as nausea, vomiting, dizziness, and headache. RESULTS This bioequivalence study was performed in 24 healthy Thai males (mean [SD] age, 20.5 [1.3] years; range, 19-24 years; weight, 62.5 [7.4] kg; height, 172.8 [6.9] cm; body mass index, 20.9 [2.0] kg/m(2)). The mean (SD) C(max) and T(max) of the test formulation of lamotrigine were 1.7 (0.3) microg/mL and 1.2 (0.9) hours, respectively. The mean (SD) C(max) and T(max) of the reference formulation of lamotrigine were 1.7 (0.3) microg/mL and 1.4 (1.0) hours, respectively. The mean (SD) AUC(0-t) was 67.1 (13.2) microg/mL x h(-1) for the test product and 66.4 (14.6) microg/mL x h(-1) for the reference product. The mean (SD) AUC(0-infinity) was 74.9 (18.3) microg/mL x h(-1) for the test product and 74.3 (20.5) microg/mL x h(-1) for the reference product. The mean (SD) t((1/2)) values were 35.0 (7.6) hours for the test product and 34.7 (7.6) hours for the reference product. The mean test/reference ratios for AUC(0-t), AUC(0-infinity), and Cmax were 1.01, 1.01, and 1.05, respectively. The parametric 90% CIs for AUC(0-t), AUC(0-infinity), and Cmax were 0.98 to 1.05, 0.98 to 1.06, and 0.98 to 1.13, respectively. Following administration, dizziness or headache was reported in 2 subjects in the test group and 1 subject in the reference group. CONCLUSION The results of this study suggest that the test product was bioequivalent to the reference product in these healthy Thai male subjects, based on the US FDAs regulatory definition.

Beating heart as an alternative for closure of secundum atrial septal defect.

We repaired secundum atrial septal defect in 135 consecutive patients from February 2003 to December 2010. There were 98 females and 37 males, with a mean age of 22.92 ±17.46 years (range, 3–55 years). To prevent myocardial dysfunction and systemic embolism caused by the conventional technique, the operation was performed with a beating heart under cardiopulmonary bypass in 63 cases, and compared the data retrospectively with cases treated under aortic crossclamping, to determine the safety of the beating-heart technique and to evaluate risk factors for embolism in stroke patients. Patient age and size of defect were similar in both groups. There was no death and no residual shunt in either group. The mean cardiopulmonary bypass time was 36.84 ± 9.8 min in the beating-heart group and 43.13 ± 16.7 min in the crossclamp group. The ejection fraction and the incidence of postoperative arrhythmia were similar in both groups. There were no differences in blood products transfused, intensive care unit stay, hospital stay, or perioperative morbidity. In our experience, the results of the beating-heart technique were not different from the conventional technique.

Mediastinal teratoma in a neonate with acute respiratory failure

Abstract Background: While teratomas account for the leading cause of germ cell tumors, the mediastinal teratomas represent one of the infrequent types of congenital germ cell tumors. Neonates with large mediastinal teratomas generally show severe respiratory distress, and the immediate surgical treatment is needed to alleviate their problems. Objectives: Report clinical symptoms, diagnostic procedures, treatment option, and outcomes after the treatment for a neonate with a large mediastinal teratoma. Methods: A 2-day-old female infant presented with acute respiratory failure diagnosed as mediastinal teratoma. It was followed with surgical treatment. The removed tissues were examined pathologically. Results: The girl suffered an acute respiratory failure two days after birth. The chest radiography, echocardiography, and chest computerized tomography results showed the considerable size of the mediastinal teratoma. A median sternotomy was performed on the third day of infant life to remove the tumor without rupturing the capsule. Pathological diagnosis was germ cell tumor. Clinical follow-ups reported no complication. Conclusion: The successful management of a neonate with large mediastinal teratomas was presented. Immediate detection and proper treatment of the large mediastinal teratoma in a neonate was most important to decrease the morbidity and mortality of the infant.

The prevalence of unrecognized congenital heart disease among healthy elementary school students in northern Thailand

Background: Congenital heart disease (CHD) is one of the major congenital anomalies among newborns. Although many infants with CHD are symptomatic and identified soon after birth, others remain undiagnosed until the disease becomes severe. Objectives: Unravel the number of CHD cases among 7-12 years old students who reported neither clinical complication nor history about cardiac diseases, stressing the importance for regular cardiac examination in children, even if they appeared healthy. Methods: The study selected students without clinical history of heart disease from 1,041 elementary schools in northern Thailand (Tak, Nakhon Sawan and Uttaradit). Certified nurses and health officers examined the students for abnormal heart conditions. Pediatric cardiologists scrutinized the students with suspected CHD for confirmation and characterization of cardiac lesion types. Results: Out of 144,293 students included in the study, 851 students showed atypical heart symptoms, and 87 were verified to have the CHD. This conferred the prevalence rate of unrecognized CHD among the elementary school children to be 0.60 per 1,000. The frequently-detected heart defects were ventricular septal defect (41.4%) and pulmonary stenosis (16.1%). Fifty-one children (58.6%) required surgery for cardiovascular correction. The prevalence of the CHD in elementary school students ranged from 0.41 to 1.05 cases per 1000 study subjects. The greatest number of incidences was found in Tak province where medical resources are inadequate. Conclusion: This study highlights the significance of routine cardiac examination among school-aged students, particularly in the regions with limited medical facilities, providing information essential for appropriate health care planning and managements.

Epidemiology and Etiology of Congenital Heart Diseases

Congenital heart disease (CHD), the most common type of birth defect, is an abnormal cardiocirculatory structure or function present at birth, although the disease is often discovered later in life. During prenatal life, the incidence of cardiac defect is higher due to affected fetuses that are aborted. CHD stems from an alteration in the embryonic development from a normal structure, or a failure of a structure to properly develop beyond an early stage of embryonic and fetal development. The non-typical patterns of cardio-circulatory flow owning to an anatomical defect may significantly influence the structural and functional development of the remainder of the circulatory system. Additionally, postnatal events have a marked impact on the clinical presentation of a specific isolated malformation. As CHD accounts for the most frequent cause of lethal malformation among infants, CHD is also considered a major problem affecting public health worldwide (Bernier et al., 2010). Despite the continuing progress in non-surgical and surgical treatments that allow for the survival of the majority of patients, some complex heart diseases are still associated with substantial morbidity and mortality. According to a report, 45% of infant deaths owing to congenital anomalies were caused by CHD in Western Europe. In Latin America, North America, Eastern Europe and the South Pacific region (including Japan) this proportion has been reported to be 35%, 37%, 42% and 48%, respectively (Botto, 2003). 20% of spontaneous abortions and 10% of stillbirths are attributed to CHD (Botto, 2001). CHD causes high morbidity and mortality among infants, and affects the quality of life during childhood and adulthood, depending on the progression of the disease (Majnener et al., 2008). It also affects social interactions and the quality of life for parents of children with CHD. While newborns with the cardiac disorder are symptomatic and identified soon after birth, many others are not diagnosed until the disease progresses into a severe stage. Data from the Northern Region Pediatric Cardiology database suggest around 1 in 4 cases of congenital heart disease in the UK are diagnosed later in childhood (Petersen et al., 2003). The signs and symptoms of heart disease depend on the type and severity of the disease. Children with critical cardiac lesion generally exhibit high morbidity and mortality because the risk of morbidity and mortality increases as treatment and diagnosis is delayed. The screening process is very important to detect congenital heart malformations. One of the major contributors to increased mortality and morbidity is clinical deterioration and heart