Pharmacokinetics of chloroquine and primaquine in healthy volunteers

Background Vivax malaria is a neglected disease. There is an irrefutable need for better treatments with higher acceptability and efficacy. The treatment efficacy is influenced by many factors, including bioavailability. Hence, a straightforward strategy to improve vivax malaria treatment efficacy is the deployment of good quality formulations of primaquine and chloroquine. As these treatments were developed more than 70 years ago, many of the available data on blood levels of both drugs are based on obsolete analytical methodologies or pharmaceutical formulations, which are not available anymore. Herein, the results of three bioequivalence studies are presented, providing individual pharmacokinetic data on chloroquine and primaquine of more than a hundred healthy volunteers and using up-to-date analytical methods. Methods Three trials were designed as a single centre, randomized, single dose, open label, fasting, crossover bioequivalence studies comparing a new coated chloroquine tablet to the uncoated tablet, and 5 and 15 mg primaquine formulations to either an international reference product or the currently distributed tablets. Plasma concentrations of chloroquine and primaquine were measured using a validated HPLC–MS/MS method in accordance with current international regulatory requirements for bio-analytical methods. Results In total, a hundred eleven healthy volunteers of both genders were included in the three studies (n = 32; 30 and 56 respectively). No serious adverse events occurred. Drugs levels were measured in 5,520 blood samples. The estimated ratio of the geometric means of Cmax, AUC0-t and AUC0-inf of test and reference drugs and their 90% CI for chloroquine 150 mg, primaquine 15 mg and primaquine 5 mg were: 95.33% (89.18; 101.90), 86. 85% (82.61; 91.31), and 84.45% (76.95; 92.67); 93.28% (81.76; 106.41), 94.52% (86.13; 103.73) and 93.93% (85.83; 102.79); 97.44% (90.60; 104.78), 93.70% (87.04; 100.87) and 91.36% (85.27; 97.89), respectively. As Cmax and AUC0-t 90% CI were within the acceptance interval of 80–125% in all cases, the formulations tested were bioequivalent. Conclusions In conclusion, the three studies provided detailed chloroquine and primaquine pharmacokinetic data in accordance with current regulatory standards. Together with other open data initiatives, this individual data may increase the accuracy of pharmacokinetic models guiding best dose, new combinations, regimens and formulations to optimize the current chloroquine and primaquine treatments for vivax malaria. The data presented here may support the deployment of high-quality drugs and evidence-based public health policies.

Current Prospects of Herbal STW 5 Agent in Treatment of Functional Gastrointestinal Diseases

Aim. A review of current therapeutic perspectives of the herbal STW 5 medicine (Iberogast®) in functional gastrointestinal (GI) diseases.Key points. A limited remediation in most common functional GI diseases, functional dyspepsia (FD) and irritable bowel syndrome (IBS), is conditioned by their multifactorial pathogenesis. Meanwhile, most specific medicines only target selected pathogenesis components, thus warranting a multitarget agent development. Such is Iberogast® that acts at variant components of FD and IBS pathogenesis. The article reviews the Iberogast® mechanisms of action and evaluates its treatment efficacy in FD and IBS.Conclusion. The current evidence claims that Iberogast® provides an effective and safe treatment for FD and IBS.

Clinical Efficacy of Conventional Heparin Anticoagulation Combined with Apixaban in the Treatment of Patients with Cerebral Venous Thrombosis and Its Effect on Serum D-Dimer and FIB Expression

Objective. The aim of this study was to explore the clinical efficacy of conventional heparin anticoagulation in combination with apixaban in the treatment of patients with cerebral venous thrombosis (CVT) and its influence on serum D-dimer (D-D) and fibrinogen (FIB). Methods. One hundred and fifty-seven consecutive CVT patients admitted to our hospital from January 1, 2006, to December 31, 2013, were allocated into two groups according to the different treatment methods, of which 95 cases received standard anticoagulation therapy (standard group (SG)) and the remaining 62 cases were given apixaban therapy (research group (RG)). The curative effects and the changes of coagulation function during the treatment, as well as the incidence of adverse reactions, were analyzed in the two groups. The changes of D-D and FIB levels before treatment and at days 1, 4, and 7 posttreatment were detected. Results. In treatment efficacy, RG was superior to SG. No evident difference was observed in the incidence of adverse events or coagulation function between the two groups. At day 1 posttreatment, D-D level was increased largely in both SG and RG, but the increase was much more significant in RG. However, D-D level was decreased gradually with time in both groups, and the reduction was more notable in RG. The FIB level in SG declined gradually with time after treatment and was higher than that in RG at the same time point. In RG, FIB was decreased gradually at day 1 and day 4 posttreatment, and its level at day 7 posttreatment showed no difference compared with that at day 4 posttreatment. Spearman’s analysis identified that the higher the D-D level or the lower the FIB level at day 1 posttreatment was, the better the treatment efficacy was. After seven-day treatment, the lower the level of D-D and FIB was, the better the therapeutic effect was. Logistic analysis indicated that age, time of diagnosis, deep vein thrombosis (DVT), Glasgow Coma Scale (GCS) score, infection, Apixaban, D-D, and FIB all independently affect the treatment effect of patients. Conclusions. The combined use of Apixaban with heparin is high-performing and safe in the treatment of CVT. The changes of D-D and FIB levels during the treatment are strongly linked to the therapeutic effect, which can be used as plausible evaluation indexes for the efficacy of CVT.

What Is Valued Most by Patients With Type 2 Diabetes Mellitus When Selecting Second-Line Antihyperglycemic Medications in China

Objective: To estimate patient preferences for second-line antihyperglycemic medications in China.Methods: A face to face survey with the best-worst scaling (BWS) choices was administered in patients with diagnosed type 2 diabetes mellitus (T2DM). Study participants were asked to indicate which attribute they valued most and which attribute they valued least in 11 choice sets, each of which consisted of five alternatives out of 11 antihyperglycemic medication-specific attributes (treatment efficacy, weight change, hypoglycemic events, gastrointestinal side effects, cardiovascular health, urinary tract infection and genital infection side effects, edema, mode of administration, bone fracture, dosing frequency and out-of-pocket cost). A counting approach, a conditional logit model, and K-means clustering were used to estimate the relative importance of items and preference heterogeneity.Results: A total of 362 participants were included with a mean age of 63.6 (standard deviation: 11.8) years. There were 56.4% of participants were women, and 56.3% being diagnosed with diabetes for at least 5 years. Efficacy, cardiovascular health and hypoglycemic events were valued most, while dosing frequency, mode of administration and bone fracture were valued least. The K-means clustering further showed preference heterogeneity in out-of-pocket cost across the participants.Conclusion: Our study suggests that treatment efficacy, cardiovascular health and hypoglycemic events are valued most by Chinese patients with T2DM when selecting second-line antihyperglycemic medications. The study improves the understanding of patients’ preferences for second-line antihyperglycemic medications in China.

Usefulness of combined handheld ultrasound and fluoroscopy-guided injection in adhesive capsulitis of the shoulder: A prospective, randomized single blind-pilot study

BACKGROUND: Ultrasound is increasingly being utilized in the diagnosis and treatment of adhesive capsulitis. OBJECTIVE: To compare the therapeutic effects and advantages of combined handheld ultrasound and fluoroscopy-guided intra-articular corticosteroid injection with those of conventional ultrasound-guided corticosteroid injection in adhesive capsulitis of the shoulder. METHODS: A total of 39 patients diagnosed with adhesive capsulitis of the shoulder were randomly assigned into two groups. Group A patients (n= 19) underwent combined handheld ultrasound and fluoroscopy-guided corticosteroid injection and group B patients (n= 20) underwent conventional ultrasound-guided corticosteroid injection to the intra-articular space of the shoulder twice. Treatment efficacy was assessed at 2 and 6 weeks after the final injection, based on the verbal numeric pain scale, Shoulder Pain and Disability Index, and range of motion. Secondary outcome measures were the accuracy and procedure time. RESULTS: Both injection methods were effective in the treatment of adhesive capsulitis. No significant differences in treatment efficacy and injection accuracy were observed between the two groups (p> 0.05). CONCLUSIONS: This study showed no statistical differences in treatment efficacy between 2 groups. However, the combined use of ultrasound and fluoroscopy can increase the accuracy of injection compared with conventional ultrasound alone.

BIOECOLOGICAL DEVELOPING PECULIARITIES OF MELON FLY AND CONTROLLING ACTIONS

The article describes the development of biological and ecological features and harmfulness of melon fly on crops of melons in conditions of Karakalpakstan. It is studied the efficiency of the deep autumn plowing of soil against overwintering pests, special traps to kill the larvae and pupae, chemical treatments against the imaginal phase melon fly on crops of melon. The impact on the conservation of wild melon pest overwintered individuals. Recommended optimal protective measures in extreme conditions of Karakalpakstan. KEYWORDS. Melon fly, melon, pest, biological, chemical treatment efficacy.

Therapeutic Response of CCKBR-Positive Tumors to Combinatory Treatment with Everolimus and the Radiolabeled Minigastrin Analogue [177Lu]Lu-PP-F11N

The inhibition of the mammalian target of rapamycin complex 1 (mTORC1) by everolimus (RAD001) was recently shown to enhance the tumor uptake of radiolabeled minigastrin. In this paper, we investigate if this finding can improve the in vivo therapeutic response to [177Lu]Lu-PP-F11N treatment. The N-terminal DOTA-conjugated gastrin analogue PP-F11N (DOTA-(DGlu)6-Ala-Tyr-Gly-Trp-Nle-Asp-Phe) was used to evaluate treatment efficacy in the human A431/CCKBR xenograft nude mouse model in combination with RAD001. Both RAD001 and [177Lu]Lu-PP-F11N single treatments as well as their combination inhibited tumor growth and increased survival. In concomitantly treated mice, the average tumor size and median survival time were significantly reduced and extended, respectively, as compared to the monotherapies. The histological analysis of kidney and stomach dissected after treatment with RAD001 and [177Lu]Lu-PP-F11N did not indicate significant adverse effects. In conclusion, our study data demonstrate the potential of mTORC1 inhibition to substantially improve the therapeutic efficacy of radiolabeled minigastrin analogues in CCKBR-positive cancers.