Safety, pharmacokinetics and pharmacodynamics of HWH486 capsules in healthy adults: A randomized, double-blind, placebo-controlled, phase I dose-escalation study.

OBJECTIVES: HWH486 inhibits Bruton's tyrosine kinase and therefore shows promise as a treatment against rheumatoid arthritis and chronic spontaneous urticaria. This phase I trial assessed tolerability, safety, pharmacokinetics and pharmacodynamics of a single oral dose of HWH486 capsules in healthy adults. METHODS: A single-center, randomized, double-blind, placebo-controlled, dose-escalation study from 10 to 800 mg was conducted in 96 healthy Chinese adults, of whom 80 received HWH486 and 16 received placebo. RESULTS: A total of 96 subjects were enrolled, and all completed the study. In the HWH486 group, mean Tmax ranged from 1.03 to 2.00 h, and mean T1/2 ranged from 0.85 to 8.67 h across the dose range from 10 to 800 mg. Mean Cmax increased linearly with dose, while mean AUC0-t increased non-linearly. Occupancy of Bruton's tyrosine kinase peaked within 0.50-4.00 h after administration across the dose groups, and the delay until peak occupancy decreased with increasing dose. Twenty-five subjects (31.25 %) in the HWH486 group experienced 35 treatment-emergent adverse events, while four subjects (25.00 %) in the placebo group experienced eight such events. CONCLUSIONS: HWH486 is well tolerated and safe in healthy adults, in whom it can strongly bind Bruton's tyrosine kinase. These findings justify clinical studies of HWH486 efficacy against autoimmune diseases.

Comparative Pharmacokinetics and Safety of Imrecoxib, a Novel Selective Cyclooxygenase-2 Inhibitor, in Elderly Healthy Subjects.

Background: Imrecoxib is a novel and moderately selective cyclooxygenase-2 inhibitor with properties of anti-inflammation and alleviating pain, which is widely applied in osteoarthritis patients. The pharmacokinetic data supporting imrecoxib's rational use in elderly population are not available. Purpose: The study aims to investigate the pharmacokinetics of imrecoxib and its main metabolites and explore the safety of imrecoxib in elderly healthy subjects. Methods: A total of 19 healthy subjects including 10 non-elderly and 9 elderly subjects received single dose of 100 mg imrecoxib under fasting condition. Pharmacokinetics, safety and tolerability profiles were assessed. Results: After oral administration of single dose of 100 mg imrecoxib, it was absorbed into plasma with median time to reach peak concentration (Tmax) around 2 hours. The concentration-time curves of imrecoxib (M0) showed higher interindividual variability in elderly subjects compared with non-elderly subjects. Peak concentration (Cmax) of M0, its hydroxyl metabolite M1 and carboxylated metabolite M2 in plasma increased by 39%, 21% and 17%, and area under concentration-time curve from time 0 to time t (AUC0-t) of M0, M1 and M2 in plasma increased by 34%, 13% and 27%, respectively, in elderly subjects compared with non-elderly subjects. The 90% CIs of geometric mean ratios of Cmax, AUC0-t and AUC0-∞ of M0, M1 and M2 between the two groups were not located within 80-125%, indicating Cmax, AUC0-t and AUC0-∞ were not completely equivalent between non-elderly and elderly healthy subjects. However, comparison of pharmacokinetic data of M0, M1 and M2 between the two groups showed no significant difference (P>0.05). Imrecoxib was well tolerated in both non-elderly and elderly healthy subjects, especially with favorable gastrointestinal and cardiovascular safety profiles. Conclusion: Pharmacokinetic and safety profiles of imrecoxib in elderly healthy subjects indicated that no dose adjustment should be required for elderly population.

Randomized, double-blinded, placebo-controlled phase I study of the pharmacokinetics, pharmacodynamics, and safety of KL130008, a novel oral JAK inhibitor, in healthy subjects.

BACKGROUND AND OBJECTIVES: KL130008 is a novel selective inhibitor of Janus kinase (JAK) 1/2 that may have therapeutic benefit against rheumatoid arthritis (RA) and other autoimmune diseases. Here, we developed a first-in-human trial of KL130008 to evaluate its pharmacokinetics (PK), pharmacodynamics (PD), and safety in healthy subjects. METHODS: Randomized, double-blinded, placebo-controlled phase I study was designed. Healthy Chinese subjects received KL130008 in single-ascending doses (1-20 mg) or multiple-ascending doses (2-6 mg) once daily for seven days, and data on PK, PD, and safety data including QT interval were evaluated. RESULTS: A total of 79 subjects were enrolled, of whom 77 completed the study. After oral administration following at least a 10-h fast, KL130008 was rapidly absorbed and reached a maximum concentration (Cmax) in 0.6-1.5 h. KL130008 exposure was approximately linear and dose-proportional. The drug showed exponential elimination with t1/2 = 14-18 h, and 8-20% of KL130008 was excreted in the urine. Dose-dependent inhibition of the phosphorylated signal transduction and transcriptional activator 3 (p-STAT3) was observed in subjects who received single KL130008 doses of 4-20 mg, while multiple dosing of KL130008 at 2, 4, or 6 mg once daily for seven consecutive days sustainably inhibited p-STAT3. The rates of treatment-emergent adverse events were 88.7% with KL130008 and 81.3% with placebo. All such events were grade 1 or 2 and disappeared or resolved by the end of the study. The most frequent such events were a decrease in neutrophil percentage, which occurred in 30.6% of subjects on KL130008; a decrease in neutrophil count, which occurred in 29.0% of subjects on KL130008; and an increase in lymphocyte percentage, which occurred in 25.8% of subjects on KL130008. None of these three events occurred while subjects were on placebo. CONCLUSION: Our results support that KL130008 is a safe and well-tolerated oral JAK1/2 inhibitor. The present study may help optimize the KL130008 dosing regimen for a phase II study. CLINICAL TRIAL REGISTRATION NUMBER: ChiCTR1800018743 (chictr.org); registered on October 7, 2018.

Sedation Effects Produced by a Ciprofol Initial Infusion or Bolus Dose Followed by Continuous Maintenance Infusion in Healthy Subjects: A Phase 1 Trial.

INTRODUCTION: The effects of continuous infusions of ciprofol on its pharmacodynamic and pharmacokinetic properties and safety profiles in healthy Chinese subjects were evaluated. METHODS: In this open-label, randomized, two-way cross-over study, subjects received initial doses of continuous ciprofol/propofol as an infusion for 30 min in part 1 (n = 8) and a bolus dose in part 2 (n = 8) followed by maintenance infusions for a total of 4 h in part 1 and 12 h in part 2. Each subject participated in both parts with a washout time of at least 40 h. RESULTS: The safety and tolerability parameters of ciprofol were similar to those of propofol, and all treatment-emergent adverse events were mild. The incidences of injection pain and respiratory depression in subjects given ciprofol were lower than those receiving propofol. The pharmacokinetic parameters Cmax, tmax, t1/2, λz and MRT for ciprofol and propofol were similar, while CL, Vd and Vss were statistically significantly different. Pharmacodynamic parameters including the Richmond Agitation Sedation Scale and bispectral index profiles of ciprofol were similar to those of propofol. CONCLUSION: Ciprofol has potential for clinical application for continuous intravenous infusion to maintain sedation for 12 h with the same safety, tolerability and efficacy as propofol.

Bioequivalence of 2 Aripiprazole Orally Disintegrating Tablets in Healthy Chinese Volunteers Under Fasting and Fed Conditions.

To assess the bioequivalence of 2 formulations of aripiprazole orally disintegrating tablets and to monitor their safety and tolerability in Chinese subjects, a single-site, open-label, randomized, 2-preparation, single-dose, 2-period crossover design was conducted. All 60 subjects were randomly divided into the fasting group and the fed group. Blood samples were collected at scheduled times after a single oral dose of orodispersible tablets containing 10 mg of aripiprazole. In the fasting state, the geometric mean ratios (90% confidence intervals [CIs]) of the test/reference formulation were 92.22%-100.20% for the area under the concentration-time curve (AUC) from time zero to the last measured concentration (AUC0-t ), 91.73%-100.14% for the AUC from administration to infinite time (AUC0-∞ ), and 98.52%-112.52% for the maximum plasma concentration (Cmax ). In the fed state, AUC0-t , AUC0-∞ , and Cmax were 92.23%-100.20%, 91.73%-100.14%, and 95.91%-105.13%, respectively. The 90%CIs of the test/reference AUC ratio and Cmax ratio were within the acceptance range of 80.00%-125.00% for bioequivalence. Neither the maximum peak plasma concentration (tmax ) nor the terminal elimination half-life (t1/2 ) showed any significant difference. No serious adverse events) were encountered during the study. The test and reference formulations were bioequivalent under both fasting and fed conditions and were found to be safe and tolerated.

The safety and tolerability of alkaloids from Alstonia scholaris leaves in healthy Chinese volunteers: a single-centre, randomized, double-blind, placebo-controlled phase I clinical trial.

CONTEXT: Capsule of alkaloids from the leaf of Alstonia scholaris (L.) R.Br. (Apocynaceae) (CALAS) is a new investigational botanical drug (No. 2011L01436) for bronchitis, post-infectious cough and asthma. OBJECTIVE: To observe the clinical safety and tolerability of CALAS. MATERIALS AND METHODS: Subjects were assigned to eight cohorts, and each received randomly CALAS or placebo in one of single ascending dose (SAD) of 8, 40, 120, 240, 360, 480, or in one of multiple ascending dose (MAD) of 40 or 120 mg, three times daily for 7 days. Each cohort contained two placebo subjects. RESULTS: Sixty-two enrolled volunteers completed the study and no serious adverse events and clinically significant changes in vital signs, electrocardiography, and upper abdominal Doppler ultrasonography were observed. The ratios of treatment-emergent adverse events (TEAEs) were reported in 11/46 (23.91%) of CALAS groups and 3/16 (18.75%) of the placebo group (p > 0.05), respectively, based on the results of SAD and MAD. All TEAEs were mild, transient, and disappeared without any intervention. The TEAEs possibly related to CALAS treatment were as followings: hiccups (4/46: 8%), dry mouth and nausea (3/46: 6%), increased sleep (2/46: 4%), abdominal distension (1/46: 2%), bilirubin elevated (1/46: 2%). DISCUSSION AND CONCLUSIONS: CALAS is safe and well-tolerated with no unexpected or clinically relevant safety concerns up to a single dose of 360 mg and three times daily for 7 days up to 120 mg in healthy Chinese volunteers, supporting further Phase II studies.

Pharmacokinetics and safety of tiotropium+olodaterol 5 µg/5 µg fixed-dose combination in Chinese patients with COPD.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is one of the major causes of morbidity and mortality worldwide and in China. For patients with more severe symptoms, initial treatment with long acting ß2-agonists and long-acting muscarinic antagonists combination therapy is recommended. Tiotropium + olodaterol fixed-dose combination (Tio + Olo FDC) is an aqueous solution of tiotropium bromide and olodaterol delivered by the RESPIMAT® Soft Mist™ inhaler for patients with moderate to very severe COPD. METHODS: This single site, open-label, phase Ib clinical study assessed the pharmacokinetic (PK) and safety profiles of once-daily Tio + Olo FDC (5 µg/5 µg) after single dose and at steady state in Chinese patients with moderate to severe COPD over 3 weeks. The PK and safety profiles of Japanese and Caucasian populations from 2 independent COPD studies were provided for comparison. RESULTS: A total of 12 Chinese patients received Tio + Olo FDC. After multiple inhaled administration of Tio + Olo FDC, tiotropium and olodaterol were rapidly absorbed and reached peak plasma concentration at about 5 and 25 min, respectively. The accumulation ratios after multiple administrations were 1.3 and 1.6 for tiotropium and olodaterol in Chinese patients. Tio + Olo FDC was well-tolerated; all AEs were mild. CONCLUSION: Tio + Olo FDC (5 µg/5 µg) was rapidly absorbed and had a good safety profile in Chinese patients with COPD.

Pharmacokinetics, pharmacodynamics and safety of a novel extrafine BDP/FF/GB combination delivered via metered-dose inhaler in healthy Chinese subjects.

BACKGROUND: BDP/FF/GB pMDI is a novel triple fixed-dose combination of extra-fine inhalation aerosol beclomethasone dipropionate (BDP)/formoterol fumarate (FF)/glycopyrronium bromide (GB). Limited data on the pharmacokinetic (PK) and pharmacodynamic (PD) properties of BDP/FF/GB fixed-dose combination in healthy subjects was available. PURPOSES: This study aimed to evaluate the pharmacokinetics, pharmacodynamics and safety of BDP/FF/GB pMDI in healthy Chinese subjects. METHODS: This is an open-label, parallel-group, randomized, single and multiple dose study. In the single dose group, subjects received single supra-therapeutic inhaled dose of BDP/FF/GB pMDI (BDP/FF/GB 400/24/50 µg). In the multiple dose group, subjects received therapeutic inhaled dose of BDP/FF/GB pMDI (BDP/FF/GB 200/12/25 µg), twice daily, for 7 consecutive days. Plasma BDP, B17MP, formoterol and GB were determined by a validated ultra performance liquid chromatography method with tandem mass spectrometric detection (UPLC/MS-MS). Heart rate (HR), QTcF, systolic blood pressure (SBP) and diastolic blood pressure (DBP) were evaluated as the surrogate indicators of pharmacodynamic effects. RESULTS: A total of 24 subjects were randomized and 22 (11 in each group) completed the study. The dose adjusted pharmacokinetic profiles of BDP, beclomethasone-17-monopropionate (B17MP, the most active metabolite of BDP), formoterol and GB were overall similar in therapeutic and supra- therapeutic dose group, showing dose proportional increase of the systemic exposure to BDP, B17MP, formoterol and GB. The pharmacodynamic variables were within the normal range and showed no significant difference between the two groups. All the treatment-emergent adverse events (TEAEs) were mild and no severe TEAE was reported. CONCLUSIONS: Dose adjusted PK profiles were similar between therapeutic and supra-therapeutic dose for all compounds, nearly dose proportional systemic exposure to B17MP, formoterol and GB after BDP/FF/GB pMDI administration in healthy Chinese subjects. BDP/FF/GB pMDI was safe and well tolerated in healthy Chinese subjects. The PK profiles were comparable to previously published data from Western European healthy Caucasian subjects.

Pharmacokinetics and Bioequivalence Evaluation of a New Oxycodone Tamper-Resistant Tablet Administered with an Opioid Antagonist in Patients with Chronic Pain.

BACKGROUND AND OBJECTIVES: Oxycodone tamper resistant (OTR) is a new extended-release abuse-deterrent formulation providing improvements in the tamper resistant characteristics. This study aimed to investigate the pharmacokinetic properties of the new OTR tablets and evaluate the bioequivalence of oxycodone from OTR and the original extended release (ER) formulation tablets administered with an opioid antagonist in patients with chronic pain. METHODS: In this open-label, randomized, cross-over study, the enrolled patients were randomised to receive a single dose of 40 mg OTR or 40 mg OXYCONTIN® (OXY) tablet administered with naltrexone blockade under fasting conditions. Serial blood samples for pharmacokinetic analysis were collected. Plasma oxycodone was quantified by a high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method. Tolerability was evaluated by monitoring adverse events, physical examinations, 12-lead ECG and laboratory tests. RESULTS: A total of 38 patients were enrolled and 33 subjects completed the study. After a single dose of 40 mg tablets, pharmacokinetic results of the new OTR tablet were found to be similar to those of original extended-release oxycodone tablet. OTR 40 mg was bioequivalent to OXY 40 mg and was well tolerated in patients with chronic pain. CONCLUSIONS: The new OTR formulation could provide a new choice in the treatment of chronic pain and reduce the potential for oxycodone abuse. Chictr.org identifier: ChiCTR1800017253.

[Pharmacokinetics of Phosphate Retagliptin Tabletin in Patients with Renal Dysfunction].

OBJECTIVE: To compared the differences in pharmacokinetics of phosphate retagliptin tablets in patients with varying degrees of renal dysfunction. METHODS: A total of 32 patients were categorized into five groups according to their renal function: normal,mild dysfunction, moderate dysfunction,severe dysfunction,and end stage renal dysfunction (ESRD). All of the patients took a single dose of 50 mg phosphate retagliptin tablet. Their plasma and urinary concentrations of phosphate retagliptin (SP2086) and phosphate retagliptin acid (SP2086 acid) were determined using LC-MS/MS methods. The plasma pharmacokinetic parameters were calculated using WinNolin 6.1 software. RESULTS: Peak concentrations (Cmax) of SP2086 reached at (1.07±0.35) h in the patients with mild renal dysfunction,(1.50±0.89) h in the patients with moderate renal dysfunction,(1.67±2.16) h in the patients with severe renal dysfunction,(2.42±2.15) h in the patients with ESRD,and (1.75±1.21) h in the normal participants,with a clearance (CL/F) of (23.50±6.01) ,(12.90±4.34) ,(6.70±1.55) ,(3.10±0.48) ,and (30.50±10.70) L/h,respectively. With the increasing damages in renal function presented an incease in Cmax,time to reach Cmax (Tmax),and area under curve (AUC), a decrease in CL/F, of SP2086 and SP2086 acid. The 0-96 hurine cumulative excretion percentage (Ae%) of SP2086 ranged from 0.441% to 4.530%. The Ae% of SP2086 acid reached (71.7±14.3) % in the patients with mild renal dysfunction, (59.5±22.7) % in the patients with moderate renal dysfunction, (63.3±13.9) % in the patients with severe renal dysfunction, (34.1±20.0) % in the patient with ESRD,and (74.2±14.6) % in the normal participants, with a renal clearance (CL/R) of (220.0±51.2),(105.0±64.5),(54.5±7.6),(13.5±7.8),and (289.0±73.7) mL/min,respectively. Compared with the participants with normal renal function,the AUCs of SP2086 and SP2086 acid were 1.44 times and 2.32 times higher in the patients with moderate renal dysfunction,2.20 times and 4.39 times higher in the patients with severe renal dysfunction, and 2.83 times and 9.28 times higher in the patients with ESRD. CONCLUSION: The dosage of phosphate retagliptin tablet is recommended at 100 mg/d for patients with normal renal function and those with mild renal dysfunction,at 50 mg/d for patients with moderate renal dysfunction,and at 25 mg/d for patients with severe renal dysfunction. No phosphate retagliptin tablet is recommended for patients with ESRD.

[Pharmacokinetics Study of Phentolamine Mesylate Injection in Healthy Volunteers].

OBJECTIVE: To study the pharmacokinetic profile of phentolamine mesylate injection in healthy Chinese volunteers. METHODS: A total of 16 healthy volunteers were randomly divided into two groups, each receiving anterior teeth submucosal infiltration anesthesia and inferior alveolar nerve block anesthesia, respectively. The participants were injected with 0.9 mL, 1.8 mL, and 3.6 mL of 2% lidocaine HCl with 1∶100 000 epinephrine over three periods sequentially, followed by corresponding sequential injection of 0.2 mg, 0.4 mg, 0.8 mg of phentolamine mesylate at the same sites 30 min later.Blood samples were drawn from 5 min before injection to 15 h post the injection of phentolamine mesylate (16 time points). Adverse events were closely observed all the time. Plasma phentolamine mesylate was detected using UPLC-MS/MS with isotope as internal standard. WinNolin 6.1 software was used to calculate the pharmacokinetic parameters. RESULTS: Time to peak concerntration (Tmax) ranged from 12 to 13 min. Half-time of elimination (t1/2) ranged from 3.84 to 4.07 h, with a clearance (CL) of 190 L/h. Peak concentration (Cmax), area under concentration-time curves from 0 to t hour and from 0 to infinite time (AUC0-t and AUC0-∞) increased proportionally in the dose range of 0.2 mg to 0.8 mg. The results of confidence interval analysis showed nearly linear dynamic characteristics for the injection of phentolamine mesylate. All participants experienced mild adverse events, including pain at the injection point, dizziness, and palpitations. These adverse events disappeared without treatments. CONCLUSIONS: Phentolamine mesylate injection is effective for reversing oral local anesthetic effects.

[Bioequivalence of Ubenimex Capsules in Healthy Volunteers].

OBJECTIVE: To evaluate bioequivalence of two specifications of ubenimex capsules in comparison with the Japanese branded product (R). METHODS: The study adopted a 3-way crossover design in twenty-four healthy male volunteers, whose plasma concentrations of ubenimex were determined by UPLC-MS/MS after administration a single oral dose of 30 mg of domestic ubenimex T1 (10 mg/capsule), T2 (30 mg/capsule) and branded ubenimex R (30 mg/capsule) sequentially. The bioequivalence was evaluated using WinNonlin6. 1 statistical analysis software. RESULTS: One volunteer was excluded because of failure to follow medication instructions. The main pharmacokinetic parameters of ubenimex of T1, T2 and R were as follows: C(max) (2 646.73 ± 454.09) ng/mL, (2 675.91 ± 474.32) ng/mL and (2 432.79 ± 544.32) ng/mL, respectively; T(max) (0.68 ± 0.23) h, (0.76 ± 0.19) h and (0.77 ± 0.26) h, respectively; AUC(0-t) (3 925.23 ± 478.34)(ng x h)/mL, (3 804.62 ± 448.84)(ng x h)/mL and (3 789.30 ± 443.15)(ng x h)/mL, respectively; AUC(0-∞)(3 938.31 ± 479.54)(ng x h)/mL, (3 817.26 ± 450.90) (ng x h)/mL and (3 800.90 ± 444.77) (ng x h)/mL, respectively; CL/F (7.72 ± 0.92) L/h, (7.97 ± 0.98) L/h and (7.99 ± 0.90) L/h, respectively; Vd (26.08 ± 9.20 )L, (25.65 ± 10.22) L and (26.03 ± 10.05) L, respectively. The relative bioavailability F(0-t) and F(0-∞) of T1 and T2 against the branded preparation R were (103.90 ± 9.19)% and (100.77± 9.36)%, and (103.93 ± 9.20)% and (100.79 ± 9.33)%, respectively. CONCLUSION: Both ubenimex capsules T1 and T2 are bioequivalent to the Japanese branded products.

[Pharmacokinetics study of injected doripenemin healthy volunteers].

OBJECTIVE: To study the pharmacokinetics of injected doripenem in Chinese healthy volunteers, in order to optimize dosages for patients. METHODS: Twelve healthy volunteers were recruited in the threecross Latin square designed study. Participants received intravenous infusions of 0.25, 0.5 and 1.0 g doripenem sequentially in three periods at a random order. Plasma and urine doripenem were measured by HPLC-UV, using an internal standard method with meropenem for plasma samples and an external standard method for urine samples, respectively. Phoenix WinNonlin 6.1 pharmacokinetic software was used to calculate non-compartment pharmacokinetics parameters. SPSS 19.0 software was used for statistical analysis. RESULTS: A single dose infusion of 0.25, 0.5 and 1.0 g doripenemin 60 min produced the following respective parameters: Cmax (11.81 +/- 1.52), (22.80 +/- 3.80) and (47.26 +/- 8.38) microg/mL, Tmax (60.42 +/- 1.44), (58.33 +/- 5.77) and (60.00 +/- 0) min, t(1/2) (63.48 +/- 10.51), (69.12 +/- 16.72) and (69.30 +/- 11.71) min, AUC(0-1), (1100.86 +/- 150.04), (2111.50 +/- 359.58) and (4359.50 +/- 789.38) microg/(mL x min). Linear Regression and Confidence Interval analyses suggested a linear kinetic characteristic. Doripenem was mainly excreted through kidneys, with 24 h cumulative urine excretion rates ranging from 70% to 75% for the three doses of infusions. It was safe to administer doripenem through infusion in healthy volunteers. Adverse reactions occurred in 19.44% cases of infusions, although all were mild reactions. Tinnitus happened in two cases (8.33%) of infusions, which required close observations. CONCLUSION: Doripenem infusion possesses a linear kinetics. There is no need to adjust the regimenpatients.

[Glycemic excursions in people with normal glucose tolerance in Chengdu].

OBJECTIVE: To investigate the characteristics of glycemic excursions in people with normal glucose tolerance (NGT) in Chengdu. METHODS: A total of 50 non-obese people with normal glucose tolerance (NGT, 23-68 years old), normal blood pressures and lipid profiles participated in the study. The fluctuations of glucose levels in the participants were measured by a continuous glucose monitoring system (CGMS) for three days 72 h. The 48 h mean blood glucose (MBG), mean amplitude of glycemic excursions (MAGE), Largest amplitude of glycemic excursions (LAGE), Postprandial peak glucose (PPG), Postprandial glucose excursion (PPGE), Mean of postprandial glucose excursion (MPPGE), and absolute means of daily differences (MODD) were measured. RESULTS: The number of glucose values detected by CGMS amounted to 861+/-7 with a mean absolute difference (MAD) of 11.3%+/-10.6%. The CGMS values were significantly correlated with the capillary glucose measurements (n=1076, r=0.761, P<0.005). The participants had a MBG of (5.9+/-1.2) mmol/L, a MAGE of (1.7+/-0.7) mmol/L, a LAGE of (4.4+/-1.9) mmol/L, a daily glycemic peak (PPG) of (8.7+/-1.7) mmol/L, a nadir level of (4.3+/-0.7) mmol/L, a MPPGE of (2.3+/-1.6) mmol/L, and a MODD of (0.75+/-0.79) mmol/L. The post-breakfast Postprandial glycemic excursions (PPGE) were lower than those of post-lunch and post-dinner (P=0.01 and P=0.05). The postprandial glucose excursions in the 60-70 year-old participants were the highest (P<0.022). In 95% (77%-100%) of the daytime, the glycose levels fluctuated between 4.1 and 8.8 mmol/L, and 78% of the participants (n=39) had hyperglycemia (BG>7.8 mmol/L) and 10% (n=5) had asymtomatic hypoglycemia (BG<2.8 mmol/L). CONCLUSION: CGMS tests may be important for detecting asymptomatic hyperglycemia and hypoglycemia. The NGT people in Chengdu have exhibited abnormal blood glucose values in CGMS, revealing problems in people with normal range of blood glucose.

Severe insulin allergy after percutaneous transluminal coronary angioplasty.

BACKGROUND: Insulin therapy is essential for type 1 and inadequately controlled type 2 diabetic patients. Insulin allergies have become less common since the introduction of highly purified human recombinant insulin. There are rare reports of severe insulin allergic reactions after percutaneous transluminal coronary angioplasty (PTCA) in patients with type 2 diabetes who had no previous allergic reactions. To better understand the causes and presentation of this rare acute reaction, we present the following observed case. CASE SUMMARY: A 63-year-old Chinese man (height, 172 cm; weight, 68.5 kg) with a 17-year history of type 2 diabetes and hypertension was first admitted to the West China Hospital, Sichuan University, Sichuan, People's Republic of China, for uncontrolled type 2 diabetes. He used regular human insulin, neutral protamine Hagedorn insulin, or premixed insulin without any allergic reactions. Four months later, PTCA was performed because of an acute myocardial infarction. The patient was administered 50 mg of protamine after active abdominal bleeding due to a right external iliac artery rupture. Three months later, recurrent raised, pruritic erythema occurred at the insulin injection site immediately after injection. Four weeks later, he experienced an attack of generalized urticaria at multiple previous injection sites (abdomen, upper arms, thighs) after injecting premixed insulin. It was accompanied by dizziness and palpitations. During the following 3 months, the symptoms recurred 3 times; one time, the patient reported losing consciousness for 2 to 3 minutes. The results of a skin prick test found that he was allergic to human recombinant insulin and insulin lispro. The allergy was resolved by changing his treatment regimen from insulin to oral hypoglycemic agents. A Naranjo score of 10 suggested a definite relationship (score >or=9) between the adverse drug reaction and the insulin administration. CONCLUSIONS: We present a definite case of allergy associated with insulin and insulin lispro administration. The patient had not experienced anaphylactic reactions prior to PTCA and protamine administration.

[The preliminary application of autologous platelet-rich gel used to treat refractory diabetic dermal ulcer].

OBJECTIVE: To assess the effectiveness and security of autologous platelet-rich gel (APG) in the treatment of refractory diabetic dermal ulcers. METHODS: Thirteen diabetic patients with refractory skin lesions were enrolled for this study, and APG was produced by platelet (PLT)-rich plasma (PRP) with thrombin and calcium gluconate. APG treatment consisted of wound dressed with APG, followed by topical washing and cleaning. The APG was then covered with Vaseline gauze and left for 48 to 72 hours, after which the wounds were treated conventionally until the next PLT-gel treatment. The clinical endpoints of the study were the healing rate. RESULTS: A total of 13 patients entered the pilot study. There were no drop-outs in the study. 69.2% ulcers were cured, and especially the ulcer areas were reduced significantly in the first 3 weeks; no adverse reactions were observed. CONCLUSION: Topical therapy with APG may be considered as an effective adjuvant method to treating refractory diabetic dermal ulcer.