Population Pharmacokinetics of Primaquine in the Korean Population.

While primaquine has long been used for malaria treatment, treatment failure is common. This study aims to develop a population pharmacokinetic model of primaquine and its metabolite, carboxyprimaquine, and examine factors influencing pharmacokinetic variability. The data was obtained from a clinical study in 24 Korean subjects randomly assigned to normal and obese groups. The participants received primaquine 15 mg daily for 4 days and blood samples were collected at day 4. Pharmacokinetic modeling was performed with NONMEM and using simulations; the influences of doses and covariates on drug exposure were examined. A minimal physiology-based pharmacokinetic model connected with a liver compartment comprehensively described the data, with CYP450 mediated clearance being positively correlated with the body weight and CYP2D6 activity score (p < 0.05). In the simulation, while the weight-normalized area under drug concentration for primaquine in the obese group decreased by 29% at the current recommended dose of 15 mg, it became similar to the normal weight group at a weight-normalized dose of 3.5 mg/kg. This study has demonstrated that the body weight and CYP2D6 activity score significantly influence the pharmacokinetics of primaquine. The developed model is expected to be used as a basis for optimal malaria treatment in Korean patients.

Pharmacodynamic evaluation of YH4808 for Helicobacter pylori eradication in healthy subjects.

YH4808 is a novel selective potassium-competitive acid blocker demonstrated to be safe and to have inhibitory effects against gastric acid secretion in previous studies. A randomized, open-label, multiple-dose, 3-treatment, 1-period, parallel design study was conducted to compare the Helicobacter pylori eradication rates and acid suppression capacities of three regimens in 60 healthy subjects with H. pylori-positive, and the potential of YH4808 to replace proton-pump inhibitors (PPIs) in standard regimens for H. pylori eradication. Group 1 received YH4808, amoxicillin, and clarithromycin as a novel triple regimen, while Group 2 received YH4808 and amoxicillin only, and Group 3 received esomeprazole, amoxicillin, and clarithromycin, as the standard triple regimen. H. pylori eradication rates were 85.0% for Group 1, 25.0% for Group 2, and 83.3% for Group 3. Relative response rate between Group 1 and 3 was 1.02 (0.50-2.07; 95% CI, χ2 test p = 0.8881). Furthermore, the novel triple regimen, YH4808, amoxicillin, and clarithromycin, stably inhibited acid secretion and maintained a gastric pH greater than 4 or 5 for 24 hours, which was comparable to the pH range in the standard triple regimen. However, the onset times of the YH4808 regimens were earlier than that for the regimens using esomeprazole. There were no differences in the incidences or severity of adverse events among the three groups. Overall, the novel triple regimen was safe and well-tolerated. YH4808 could replace PPIs in standard triple regimens used for H. pylori eradication. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01921647.

Evaluation of pharmacokinetic interactions between amoxicillin, clarithromycin, and the potassium-competitive acid blocker YH4808 in healthy subjects.

YH4808 is a novel potassium-competitive acid blocker that was developed as a therapeutic agent for gastric acid-related diseases; it may replace proton pump inhibitors, which are widely used in combination with amoxicillin and clarithromycin for Helicobacter pylori eradication. We compared the pharmacokinetic (PK) profiles and safety of amoxicillin, clarithromycin, and YH4808 used as monotherapies or in combination for evaluating potential drug interactions. An open-label, randomized, single-dose, Latin-square (4 × 4) crossover study was conducted in 32 healthy Korean volunteers. Subjects were randomly assigned to one of the 4 treatment sequences that consisted of 4 periods separated by 21-day washout intervals. PK parameters of YH4808, amoxicillin and clarithromycin administered in combination were compared with those of the respective monotherapies. The geometric mean ratios of the maximum concentration (Cmax) and the area under the time-concentration curve from time zero to time of the last quantifiable concentration (AUClast) of YH4808 increased during the triple therapy by 48.6% and 29.1%, respectively. Similarly, the Cmax and AUClast of M3 (active metabolite of YH4808) increased by 23.3% and 16.0%, respectively. The Cmax and AUClast of clarithromycin increased by 27.4% and 30.5%, and those of 14-hydroxyclarithromycin were increased by 23.1% and 32.4%, respectively. The corresponding amoxicillin values decreased during the triple therapy by 21.5% and 15.6%, respectively. There was no clinically significant change in safety assessment related to either monotherapies or triple therapy. In conclusion, amoxicillin, clarithromycin and YH4808 administered as triple therapy did not exhibit significant PK interactions and were not associated with safety issues. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01921647.

The effect of an interfragmentary gap on the clinical outcome after mandibular angle fracture surgery.

BACKGROUND/AIM: The mandibular angle fracture occasionally widens at the lower border after surgery using a single miniplate. However, the effects of an interfragmentary gap have not been fully investigated. The aim of this study was to determine the effects of gaps caused by mandibular angle fracture surgery using a single superior border miniplate technique. MATERIAL AND METHODS: In this prospective study, the interfragmentary gap was measured by panoramic radiography and cone-beam computed tomography (CBCT) postoperatively. The width of the gap measured by panoramic radiography and CBCT scans was compared. The patients were divided into two groups based on the gap width (more or less than 1.5 mm). In CBCT scans, bucco-lingual displacement of the proximal segment was evaluated. Clinical results and complication rates were investigated according to the gap and displacement. The findings were statistically analyzed. RESULTS: Thirty-two patients were included in the study. The mean interfragmentary gap widths were 1.56 ± 0.83 mm by panoramic radiography and 2.12 ± 0.87 mm by CBCT scans. CBCT measured a gap width of approximately 0.5 mm wider than panoramic radiography (P = 0.001). Twenty-two patients (68.8%) had an interfragmentary gap width of >1.5 mm, and ten patients (31.2%) had a gap width of <1.5 mm. All patients had favorable occlusion at the last clinical examination. There were no statistically significant differences in intermaxillary fixation periods and complication rates (P > 0.05). One patient in the wider gap group experienced pain in the temporomandibular joint when opening the mouth. Six patients (18.8%) had lingual displacement of the proximal fragment. Displacement did not significantly influence the complication rate (P > 0.05). CONCLUSION: The presence of an interfragmentary gap after mandibular angle fracture surgery did not affect the clinical outcome.

Simultaneous surgery for subcondylar fracture and prominent angle of the mandible.

We experienced a patient of subcondylar fracture who had a squared contour of the lower face with prominent angle of the mandible and masseter hypertrophy. Our patient was increasingly seeking esthetic improvement of the lower third of the face. But she did not want multi-stage operations. Thus, we decided and performed a one-stage mandibular angle ostectomy with fracture management. We have a stable and esthetic result simultaneously despite fractures of the fixation plates during follow-up period, so report a case.