Safety, tolerability, pharmacokinetics and pharmacokinetic-pharmacodynamic modeling of cetagliptin in patients with type 2 diabetes mellitus.

Aims: To evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of cetagliptin (CAS number:2243737-33-7) in Chinese patients with type 2 diabetes mellitus (T2DM). A population PK/PD model was developed to quantify the PK and PD characteristics of cetagliptin in patients. Materials and methods: 32 Chinese adults with T2DM were enrolled in this study. The subjects were randomly assigned to receive either cetagliptin (50 mg or 100 mg), placebo, or sitagliptin (100 mg) once daily for 14 days. Blood samples were collected for PK and PD analysis. Effects on glucose, insulin, C-peptide, and glucagon were evaluated following an oral glucose tolerance test (OGTT) (day15). Effects on HbA1c and glycated albumin (GA), and safety assessments were also conducted. Meanwhile, a population PK/PD model was developed by a sequential two-step analysis approach using Phoenix. Results: Following multiple oral doses, cetagliptin was rapidly absorbed and the mean half-life were 34.9-41.9 h. Steady-state conditions were achieved after 1 week of daily dosing and the accumulation was modest. The intensity and duration of DPP-4 inhibition induced by 50 mg cetagliptin were comparable with those induced by sitagliptin, and 100 mg cetagliptin showed a much longer sustained DPP-4 inhibition (≥80%) than sitagliptin. Compared with placebo group, plasma active GLP-1 AUEC0-24h increased by 2.20- and 3.36-fold in the 50 mg and 100 mg cetagliptin groups. A decrease of plasma glucose and increase of insulin and C-peptide were observed following OGTT in cetagliptin groups. Meanwhile, a tendency of reduced GA was observed, whereas no decreasing trend was observed in HbA1c. All adverse events related to cetagliptin and sitagliptin were assessed as mild. A population PK/PD model was successfully established. The two-compartment model and Sigmoid-Emax model could fit the observed data well. Total bilirubin (TBIL) was a covariate of volume of peripheral compartment distribution (V2), and V2 increased with the increase of TBIL. Conclusions: Cetagliptin was well tolerated, inhibited plasma DPP-4 activity, increased plasma active GLP-1 levels, and exhibited a certain trend of glucose-lowering effect in patients with T2DM. The established population PK/PD model adequately described the PK and PD characteristics of cetagliptin.

Effects of vacuum sealing drainage to improve the therapeutic effect in patients with orthopedic trauma and to reduce post-operative infection and lower-limb deep venous thrombosis.

The present study investigated the effects of vacuum sealing drainage (VSD) to improve the therapeutic efficacy in patients with orthopedic trauma (OT) and reduce post-operative infection and lower-limb deep venous thrombosis (DVT) through a retrospective analysis. A total of 76 patients with OT treated at our hospital were selected for observation. The patients were divided into the control group (CG; n=37) and the experimental group (EG; n=39) according to the treatment administered. For patients in the CG, routine dressing changes were applied. Patients in the EG underwent VSD treatment. The dressing change frequency, time between the first and second operation, hospital stay, treatment efficacy, wound healing time, interleukin-6 (IL-6) serum level, tumor necrosis factor-α (TNF-α) serum level, incidence of post-operative infection and incidence of lower-limb DVT were compared between the two groups. The dressing change frequency in the EG was less than that in the CG. The time between the first and second operation and hospital stay were shorter in the EG than in the CG (P<0.05). The total effective rate in the EG was 97.44%, which was higher than that in the CG (78.38%; P<0.05). The wound healing time in the EG was 1.72±0.73 weeks and shorter than that in the CG (2.23±0.85 weeks; P<0.05). With the progression of treatment, the serum IL-6 and TNF-α levels decreased in the two groups, but the levels in the EG were lower than those in the CG (P<0.05). The incidence of post-operative infection and lower-limb venous thrombosis in the EG were 7.69 and 0.00%, respectively, and lower than those in the CG (27.03 and 13.01%, respectively; P<0.05). In the treatment of OT, VSD may reduce the dressing change frequency, shorten the operation time and hospital stay, accelerate wound healing and reduce post-operative infection and lower-limb DVT. Thus, the VSD treatment method is worthy of promotion and implementation in clinic.

Severe traumatic valgus instability of the elbow: pathoanatomy and outcomes of primary operation.

BACKGROUND: The objective of the study was to depict the pathoanatomy of traumatic valgus instability of the elbow and to report clinical outcomes of primary operation. METHODS: Thirty-one patients presented with traumatic valgus instability of the elbow without dislocation. Thirty-one patients underwent surgical intervention of radial head fractures (28 open reduction and internal fixation and 3 radial head resection) and anatomical repair of the anterior bundle of medial collateral ligament (AMCL) with suture anchors. Twenty patients with disruption of the flexor-pronator tendon (FPT) and 14 patients with tears of the anterior capsule had primary repair of the FPT and anterior capsule simultaneously. Clinical outcomes were evaluated with the Mayo Elbow Performance Score (MEPS), modified hospital for special surgery assessment scale (HSS), and Disabilities of the Arm, Shoulder, and Hand (DASH) score. RESULTS: The median follow-up was 37.3 months (range, 15-53 months). Radial head fractures and complete avulsion of the medial collateral ligament (MCL) from its humeral footprint were confirmed in all patients intraoperatively. Intraoperative findings indicated disruption of the FPT in 20 patients and tears of the anterior capsule in 14 patients. Twenty-nine of 31 patients returned to previous activity and work levels within 6 months after surgery. The MEPS, modified HSS, and DASH score were 94 ± 4, 91 ± 5, and 8 ± 2 at the latest follow-up. CONCLUSIONS: Radial head fractures with avulsion of the MCL can lead to severe valgus instability of the elbow. Primary operation to repair these disrupted structures, especially repair of the AMCL, can effectively restore valgus stability.