[Comparison of molluscicidal cost and effectiveness between 5% niclosamide ethanolamine salt granules and 26% suspension concentrate of metalaldehyde and niclosamide ethanolamine salt].

OBJECTIVE: To compare the molluscicidal effects and cost-effectiveness of 5% niclosamide ethanolamine salt granules (NEG) and 26% suspension concentrate of metalaldehyde and niclosamide ethanolamine salt (MNSC) . METHODS: Two plots with high Oncomelania hupensis snail density were selected as research areas in Nanjing Chemical Industry Zone, and 5% NEG (40 g/m2) and 26% MNSC (40 g/m2) were used by the spraying method for snail control in the two plots, and their molluscicidal effects and cost-effectiveness were investigated and statistically analyzed. RESULTS: There was no significant difference between 5% NEG and 26% MNSC in the molluscicidal effects. The cost of 5% NEG was 1.25 times higher than that of 26% MN-SC per ten thousand square meters in snail control. CONCLUSIONS: The cost of 5% NEG is higher than that of 26% MNSC per ten thousand square meters in snail control. Their molluscicidal effects are similar.

Quality of artemisinin-based antimalarial drugs marketed in Nigeria.

Background: Artemisinin combination therapy is first-line therapy for treatment of malaria, which is one of the most significant public health problems in Nigeria. With the increasing level of use of these drugs coupled with the emergence of resistance, there is a need for regular post-market surveillance. Method: Twenty different brands of artesunate-containing antimalarial drugs and 10 brands of artemether-lumefantrine were multi-sourced in the south western part of Nigeria and were subjected to identification, weight uniformity test, and assay using United State pharmacopoeia and International Pharmacopoeia monographs. In vitro-dissolution test of the artemether tablets was also investigated. Results: All 10 brands (100%) of the artemether-lumefantrine tablets met the assay requirement for artemether and 8 (80%) met the assay requirement for lumefantrine, but only 4 brands (40%) met the requirement for artemether dissolution. One of these brands failed the weight uniformity test. Of the 20 brands of artesunate-containing brands included in this study, 15 (75%) met the standard assay requirement for artesunate and two failed the weight uniformity test. Conclusions: There is evidence of the presence of substandard artemisinin products in the Nigerian market.

Integration of novel low-cost colorimetric, laser photometric, and visual fluorescent techniques for rapid identification of falsified medicines in resource-poor areas: application to artemether-lumefantrine.

The availability of falsified antimalarial drugs can be reduced with effective drug regulatory agencies and proper enforcement. Fundamental to these agencies taking action, rapid identification must be made as soon as they appear in the market place. Since falsified antimalarials occur mostly in developing countries, performing drug analysis presents itself with unique challenges. A fundamental factor in choosing a useful technique is affordability and simplicity. Therefore, we suggest a three-tiered drug evaluation strategy for identifying a falsified drug in resource-poor areas. Tier I is a simple comparison of a tablet's weight and dimensions with official specifications. Tier II uses inexpensive photometric devices (laser and fluorescence) to evaluate a tablet. Suspicious samples from Tier I and II assessments are then subjected to a colorimetric assay for active ingredients identification and quantification. In this article, we evaluate a novel colorimetric assay for the simultaneous assessment of both lumefantrine and artemether in co-formulated Coartem™ tablets, and integrate the method with two novel, low-cost, fluorescence and laser photometric devices. Image analysis software is used for the assessments. Although artemether-lumefantrine is used as an example, the strategy may be adapted to other medicines.

Derivation of a No-Significant-Risk-Level (NSRL) for diethanolamine (DEA).

Diethanolamine (DEA) has been listed on the State of California's Proposition 65 List. This listing is based in part on tumors reported in a National Toxicology Program (NTP) 2-year dermal carcinogenicity study in mice which found clear evidence of carcinogenic activity in B6C3F1 mice based on increased incidences of liver neoplasms in both sexes, and increased incidences of renal tubule neoplasms in males. Although considerable controversy exists on the relevance of the NTP study to humans, industries are obligated to comply with the Proposition 65 labeling requirement and drinking water discharge prohibition, unless they are able to demonstrate that DEA levels in their products are below a specific No Significant Risk Level (NSRL). The State of California has not published an NSRL for DEA. In this article, a NSRL of 5.6 µg/day and a life-stage-adjusted NSRL(adj) of 1.4 µg/day are derived from the NTP carcinogenicity study using a benchmark dose modeling method based on the incidence of hepatocellular carcinomas in female mice, in accordance with the guidelines of California EPA.

Rapid and economic chiral-HPLC method of nebivolol enantiomers resolution in dosage formulation.

A fast, economic, reproducible, accurate, effective, rugged and selective chiral-HPLC method was developed and validated for the enantiomeric resolution of nebivolol enantiomers [(+)-RRRS and (-)-SSSR)] in dosage formulation. The method was rapid as chiral separation occurred within only 12 min. The mobile phase used was n-heptane-ethanol-DEA (85:15:0.1, v/v) at 3.0 mL/min flow-rate with 225 nm detection. The column used was an amylase-based 3-AmyCoat (150 × 46 mm) [tris-(3,5-dimethylphenyl carbamate)]. The capacity factors of (+)-RRRS and (-)-SSSR enantiomers were 7.85 and 10.90 while the separation and resolution factors were 1.39 and 1.83, respectively. The limits of detection and quantitation for (+)-RRRS enantiomer were 4.5 and 10.00 µg/mL, while these values for (-)-SSSR enantiomer were 4.1 and 8.2 µg/mL, respectively. The linearity was observed in the concentrations range of 0.10-1.0 mg/mL for both enantiomers. The π-π interactions, hydrogen bonds, dipole-dipole interactions and steric effects control the chiral resolution of nebivolol enantiomers on the reported chiral column. The reported method can be used for the quality control of nebivolol in pharmaceutical preparations with good economy. In addition, this method can also be used for the analysis of (+)-RRRS and (-)-SSSR) enantiomers in biological and environmental samples.

Harmonization of values for serum alkaline phosphatase catalytic activity concentration employing commutable calibration materials.

BACKGROUND: Harmonization of results allows a more effective utilization of laboratory tests; we verified the feasibility of harmonizing serum alkaline phosphatase results by two methods. METHODS: Patient sera (n=106) and candidate calibration materials (n=8) were analyzed by two methods, employing either diethanolamine (DEA) or 2-amino-2-methyl-1-propanol (AMP) as phosphate-accepting buffers. Results for patient sera by the DEA method were recalculated, with either a commutable or a non-commutable calibration material, both with values assigned by the AMP method. RESULTS: After calibration with the commutable material, the median intermethod difference (DEA-AMP) and ratio (DEA/AMP) dropped from 195 U/l to 0 U/l and from 2.47 to 1.00, respectively. When a non-commutable material was used the former became 124 U/l and the latter 1.94. After recalibration with the commutable material, linear regression and correlation analysis of DEA vs AMP values for the set of 106 patient sera gave: intercept=0.8 U/l; slope=0.997; and nonparametric correlation coefficient r=0.9995. CONCLUSIONS: Harmonization of alkaline phosphatase results by AMP and DEA methods is feasible when commutable calibration materials are used in the trueness transfer process.

Physical and chemical stability of expired fixed dose combination artemether-lumefantrine in uncontrolled tropical conditions.

BACKGROUND: New artemisinin combination therapies pose difficulties of implementation in developing and tropical settings because they have a short shelf-life (two years) relative to the medicines they replace. This limits the reliability and cost of treatment, and the acceptability of this treatment to health care workers. A multi-pronged investigation was made into the chemical and physical stability of fixed dose combination artemether-lumefantrine (FDC-ALU) stored under heterogeneous, uncontrolled African conditions, to probe if a shelf-life extension might be possible. METHODS: Seventy samples of expired FDC-ALU were collected from private pharmacies and malaria researchers in seven African countries. The samples were subjected to thin-layer chromatography (TLC), disintegration testing, and near infrared Raman spectrometry for ascertainment of active ingredients, tablet integrity, and chemical degradation of the tablet formulation including both active ingredients and excipients. RESULTS: Seventy samples of FDC-ALU were tested in July 2008, between one and 58 months post-expiry. 68 of 70 (97%) samples passed TLC, disintegration and Raman spectrometry testing, including eight samples that were post-expiry by 20 months or longer. A weak linear association (R2 = 0.33) was observed between the age of samples and their state of degradation relative to brand-identical samples on Raman spectrometry. Sixty-eight samples were retested in February 2009 using Raman spectrometry, between eight and 65 months post-expiry. 66 of 68 (97%) samples passed Raman spectrometry retesting. An unexpected observation about African drug logistics was made in three batches of FDC-ALU, which had been sold into the public sector at concessional pricing in accordance with a World Health Organization (WHO) agreement, and which were illegally diverted to the private sector where they were sold for profit. CONCLUSION: The data indicate that FDC-ALU is chemically and physically stable well beyond its stated shelf-life in uncontrolled, tropical conditions. While these data are not themselves sufficient, it is strongly suggested that a re-evaluation of the two-year shelf-life by drug regulatory authorities is warranted.

Treatment of acute uncomplicated falciparum malaria with artemether-lumefantrine in nonimmune populations: a safety, efficacy, and pharmacokinetic study.

The efficacy and safety of artemether-lumefantrine for the treatment of malaria in nonimmune populations are not well defined. In this study, 165 nonimmune patients from Europe and non-malarious areas of Colombia with acute, uncomplicated falciparum malaria or mixed infection including P. falciparum were treated with the six-dose regimen of artemether-lumefantrine. The parasitologic cure rate at 28 days was 96.0% for the per protocol population (119/124 patients). Median times to parasite clearance and fever clearance were 41.5 and 36.8 hours, respectively. No patient had gametocytes after Day 7. Treatment was well tolerated; most adverse events were mild to moderate and seemed to be related to malaria. There were few serious adverse events, none of which were considered to be drug-related. No significant effects on ECG or laboratory parameters were observed. In conclusion, the six-dose regimen of artemether-lumefantrine was effective and well tolerated in the treatment of acute uncomplicated falciparum malaria in nonimmune patients.

Efficacy and safety of the six-dose regimen of artemether-lumefantrine in pediatrics with uncomplicated Plasmodium falciparum malaria: a pooled analysis of individual patient data.

Patient data from eight clinical trials were pooled and analyzed to study the efficacy and safety of the six-dose versus four-dose regimen of artemether-lumefantrine (coartemether; Coartem) in children weighing 5-25 kg. A total of 544 patients with uncomplicated P. falciparum malaria (six-dose: 343; four-dose: 201), matched for demographic and baseline characteristics and individual coartemether doses were included in the analysis. Analysis of day 28 cure rate based on the intention-to-treat and evaluable populations yielded corrected cure rates for the six-dose regimen of 93% and 96% compared with 61% and 76%, respectively, for the four-dose regimen (P < 0.0001 for both comparisons). Similarly high cure rates were achieved with the six-dose regimen in non-immune infants weighing as little as 5 kg. The six- and four-dose regimens were equally well tolerated. The main finding of this analysis is that the six-dose regimen of coartemether is safe and more efficacious than the four-dose regimen in children.

Evaluation of procaterol and albuterol (salbutamol) aerosol in the treatment of asthma.

Procaterol aerosol (10 micrograms/inhalation) was compared to albuterol (salbutamol) aerosol (100 micrograms/inhalation), two inhalations t.i.d. or q.i.d., in 333 outpatients with reversible bronchial airway obstruction over a 12-week period in a double-blind randomized and parallel study. Predose and postdose pulmonary function tests (PFTs) were performed initially and after 2, 4, 8, and 12 weeks of therapy. Patients maintained a daily diary of asthma symptom scores. A significantly higher percentage of patients receiving procaterol (59%) continued therapy on a t.i.d. schedule rather than a q.i.d. schedule compared with patients receiving albuterol (48%, P less than .05). Pulmonary function tests indicated similar improvement in both groups. Clinically significant improvement in mean FEV1 was maintained for four to seven hours postdose for procaterol and for three to six hours for albuterol. Adverse experiences were reported in 15% of procaterol-treated patients and 17% of albuterol-treated patients. Headache and tremor were most frequent, with no significant differences in frequencies between groups. Both procaterol and albuterol were highly effective in improving pulmonary function and controlling symptoms of asthma; both were well tolerated. Procaterol had a longer duration of action, and more patients were controlled on a t.i.d. dosage regimen.

Influence of inorganic phosphate on the activity determination of isoenzymes of alkaline phosphatase in various buffer systems.

The inhibitory effect of inorganic phosphate on the activity determination of isoenzymes of alkaline phosphatase (AP) in diethanolamine (DEA), glycine and 2-amino-2-methyl-1,3-propandiol (AMPD) buffer was studied. This effect depends on the buffer used and isoenzyme investigated. Especially the placental isoenzyme is inhibited; the inhibitory effect in DEA buffer is stronger than in the other buffers used. The requirement of purity for 4-nitrophenylphosphate with respect to its content of inorganic phosphate and conclusions for using control sera enriched with AP isoenzymes are discussed.