RESUMO
BACKGROUND: When shared by people who inject drugs, needles and syringes with different dead space may affect the probability of HIV and hepatitis C virus (HCV) transmission differently. METHODS: We measured dead space in 56 needle and syringe combinations obtained from needle and syringe programs across 17 countries in Europe and Asia. We also calculated the amounts of blood and HIV that would remain in different combinations following injection and rinsing. RESULTS: Syringe barrel capacities ranged from 0.5 to 20 mL. Needles ranged in length from 8 to 38 mm. The average dead space was 3 µL in low dead space syringes with permanently attached needles, 13 µL in high dead space syringes with low dead space needles, 45 µL in low dead space syringes with high dead space needles, and 99 µL in high dead space syringes with high dead space needles. Among low dead space designs, calculated volumes of blood and HIV viral burden were lowest for low dead space syringes with permanently attached needles and highest for low dead space syringes with high dead space needles. CONCLUSION: The dead space in different low dead space needle and syringe combinations varied substantially. To reduce HIV transmission related to syringe sharing, needle and syringe programs need to combine this knowledge with the needs of their clients.
Assuntos
Desenho de Equipamento , Infecções por HIV/complicações , Uso Comum de Agulhas e Seringas/efeitos adversos , Agulhas/estatística & dados numéricos , Abuso de Substâncias por Via Intravenosa/complicações , Seringas/estatística & dados numéricos , Ásia , Europa (Continente) , Infecções por HIV/prevenção & controle , Redução do Dano , HumanosRESUMO
Among National Institutes of Health HIV Research Networks conducting multicenter trials, samples from protocols that span several years are analyzed at multiple clinical pharmacology laboratories (CPLs) for multiple antiretrovirals. Drug assay data are, in turn, entered into study-specific data sets that are used for pharmacokinetic analyses, merged to conduct cross-protocol pharmacokinetic analysis, and integrated with pharmacogenomics research to investigate pharmacokinetic-pharmacogenetic associations. The CPLs participate in a semiannual proficiency testing (PT) program implemented by the Clinical Pharmacology Quality Assurance program. Using results from multiple PT rounds, longitudinal analyses of recovery are reflective of accuracy and precision within/across laboratories. The objectives of this longitudinal analysis of PT across multiple CPLs were to develop and test statistical models that longitudinally: (1) assess the precision and accuracy of concentrations reported by individual CPLs and (2) determine factors associated with round-specific and long-term assay accuracy, precision, and bias using a new regression model. A measure of absolute recovery is explored as a simultaneous measure of accuracy and precision. Overall, the analysis outcomes assured 97% accuracy (±20% of the final target concentration of all (21) drug concentration results reported for clinical trial samples by multiple CPLs). Using the Clinical Laboratory Improvement Act acceptance of meeting criteria for ≥2/3 consecutive rounds, all 10 laboratories that participated in 3 or more rounds per analyte maintained Clinical Laboratory Improvement Act proficiency. Significant associations were present between magnitude of error and CPL (Kruskal-Wallis P < 0.001) and antiretroviral (Kruskal-Wallis P < 0.001).
Assuntos
Antirretrovirais/uso terapêutico , Infecções por HIV/tratamento farmacológico , Ensaio de Proficiência Laboratorial , Farmacologia Clínica , Controle de Qualidade , Antirretrovirais/farmacocinética , Humanos , Laboratórios , Estudos Longitudinais , Farmacogenética/métodos , Projetos de PesquisaRESUMO
Tablet formulations fail to meet the needs of patients unable to swallow tablets such as pediatric, elderly, and patients that must receive medications via feeding tubes. Our objective was to develop and test a new, simple device (XTEMP-R) and the methodology for converting tablets into a homogeneous suspension for medication administration. We developed a new device comprised of a flexible receptacle, a tight-fitting cap, and a suction cup bottom to convert tablets into liquid preparations. Tuberculosis treatment drugs, TBAJ-876 and TBI-223, were dispersed within the device utilizing water and commonly available suspending vehicles. We investigated the effectiveness of the XTEMP-R device in dispersing tablets. This was accomplished by visual observations, determining the fineness of dispersion, and measuring the total drug recovery from the dispersions in XTEMP-R. We investigated the accuracy and reproducibility of delivering aliquots from these suspensions by determining the dose reproducibility upon suspension and upon redispersion after 24 hours. The effectiveness of the device was also evaluated using commercially available tablets of acetaminophen, amlodipine, glimepiride, metformin, and valsartan. The suspensions were visually uniform without any large particles. The suspensions passed through a #18 sieve confirming that the particles were less than 1000 µm. The average total dose recovery of three suspensions each was determined to be 101.3% and 99.2% for TBI-223 and TBAJ-876, respectively. Reproducibility from aliquots of 2 mL each was 98.9% to 99.7% for three replicates of TBI-223 suspensions, and 102.6% to 103.2% for TBAJ-876 suspensions. Aliquots tested after 24 hours confirmed uniform redispersibility. We have demonstrated that XTEMP-R can be utilized to prepare homogeneous suspensions conveniently and efficiently in less than 10 minutes without any drug loss. Aliquots for partial dose delivery can be withdrawn accurately. These findings demonstrate that XTEMP-R can be used to accurately deliver doses of suspensions for patients who cannot swallow tablets.
Assuntos
Acetaminofen , Humanos , Criança , Idoso , Reprodutibilidade dos Testes , Suspensões , Composição de Medicamentos , Comprimidos , Administração OralRESUMO
BACKGROUND: Clinical trial specimens tested for antiretroviral (ARV) concentrations often require compliance with Clinical Laboratory Improvement Act and/or the Food and Drug Administration bioanalytical guidance. EXPERIMENTAL: The Clinical Pharmacology Quality Assurance Program (CPQA) designed 8 proficiency testing (PT) rounds over 4 years to assess precision, specificity and stability. RESULTS: Ten laboratories provided blinded proficiency data to support continued acceptable precision of ARV methods. Specificity samples identified little bias for individual methods; hemolyzed (87%) and lipemic (86%) results were ≤ 10% of their control results. Stability was established for ARVs in plasma at -70°C for 2.5-3.6 years. CONCLUSION: PT provided by the CPQA assured continued acceptability of individual laboratory assay performances for precision and specificity, and obtained ARV stability during long term storage.
Assuntos
Ensaio de Proficiência Laboratorial/métodos , Humanos , Controle de QualidadeRESUMO
The increasing prevalence and use of herbal mixtures containing synthetic cannabinoids presents a growing public health concern and legal challenge for society. In contrast to the plant-derived cannabinoids in medical marijuana and other cannabinoid-based therapeutics, the commonly encountered synthetic cannabinoids in these mendaciously labeled products constitute a structurally diverse set of compounds of relatively unknown pharmacology and toxicology. Indeed, the use of these substances has been associated with an alarming number of hospitalizations and emergency room visits. Moreover, there are already several hundred known cannabinoid agonist compounds that could potentially be used for illicit purposes, posing an additional challenge for public health professionals and law enforcement efforts, which often require the detection and identification of the active ingredients for effective treatment or prosecution. A solid-phase microextraction headspace gas chromatography-mass spectrometry method is shown here to allow for rapid and reliable detection and structural identification of many of the synthetic cannabinoid compounds that are currently or could potentially be used in herbal smoking mixtures. This approach provides accelerated analysis and results that distinguish between structural analogs within several classes of cannabinoid compounds, including positional isomers. The analytical results confirm the continued manufacture and distribution of herbal materials with synthetic cannabinoids and provide insight into the manipulation of these products to avoid legal constraints and prosecution.