RESUMEN
Clofazimine is included in drug regimens to treat rifampicin/drug-resistant tuberculosis (DR-TB), but there is little information about its interaction with other drugs in DR-TB regimens. We evaluated the pharmacokinetic interaction between clofazimine and isoniazid, linezolid, levofloxacin, and cycloserine, dosed as terizidone. Newly diagnosed adults with DR-TB at Klerksdorp/Tshepong Hospital, South Africa, were started on the then-standard treatment with clofazimine temporarily excluded for the initial 2 weeks. Pharmacokinetic sampling was done immediately before and 3 weeks after starting clofazimine, and drug concentrations were determined using validated liquid chromatography-tandem mass spectrometry assays. The data were interpreted with population pharmacokinetics in NONMEM v7.5.1 to explore the impact of clofazimine co-administration and other relevant covariates on the pharmacokinetics of isoniazid, linezolid, levofloxacin, and cycloserine. Clofazimine, isoniazid, linezolid, levofloxacin, and cycloserine data were available for 16, 27, 21, 21, and 6 participants, respectively. The median age and weight for the full cohort were 39 years and 52 kg, respectively. Clofazimine exposures were in the expected range, and its addition to the regimen did not significantly affect the pharmacokinetics of the other drugs except levofloxacin, for which it caused a 15% reduction in clearance. A posteriori power size calculations predicted that our sample sizes had 97%, 90%, and 87% power at P < 0.05 to detect a 30% change in clearance of isoniazid, linezolid, and cycloserine, respectively. Although clofazimine increased the area under the curve of levofloxacin by 19%, this is unlikely to be of great clinical significance, and the lack of interaction with other drugs tested is reassuring.
Asunto(s)
Antituberculosos , Clofazimina , Cicloserina , Interacciones Farmacológicas , Isoniazida , Levofloxacino , Linezolid , Tuberculosis Resistente a Múltiples Medicamentos , Clofazimina/farmacocinética , Clofazimina/uso terapéutico , Humanos , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológico , Adulto , Antituberculosos/farmacocinética , Antituberculosos/uso terapéutico , Masculino , Femenino , Linezolid/farmacocinética , Linezolid/uso terapéutico , Isoniazida/farmacocinética , Isoniazida/uso terapéutico , Levofloxacino/farmacocinética , Levofloxacino/uso terapéutico , Cicloserina/farmacocinética , Cicloserina/uso terapéutico , Persona de Mediana Edad , Sudáfrica , Adulto Joven , Quimioterapia CombinadaRESUMEN
Specific Event Identifiers a. Event type: Outdoor music festival. b. Event onset date: December 3, 2016. c. Location of event: Regatta Point, Commonwealth Park. d. Geographical coordinates: Canberra, Australian Capital Territory (ACT), Australia (-35.289002, 149.131957, 600m). e. Dates and times of observation in latitude, longitude, and elevation: December 3, 2016, 11:00-23:00. f. Response type: Event medical support. Abstract Introduction Young adult patrons are vulnerable to risk-taking behavior, including drug taking, at outdoor music festivals. Therefore, the aim of this field report is to discuss the on-site medical response during a music festival, and subsequently highlight observed strategies aimed at minimizing substance abuse harm. METHOD: The observed outdoor music festival was held in Canberra (Australian Capital Territory [ACT], Australia) during the early summer of 2016, with an attendance of 23,008 patrons. First aid and on-site medical treatment data were gained from the relevant treatment area and service. RESULTS: The integrated first aid service provided support to 292 patients. Final analysis consisted of 286 patients' records, with 119 (41.6%) males and 167 (58.4%) females. Results from this report indicated that drug intoxication was an observed event issue, with 15 (5.1%) treated on site and 13 emergency department (ED) presentations, primarily related to trauma or medical conditions requiring further diagnostics. CONCLUSION: This report details an important public health need, which could be met by providing a coordinated approach, including a robust on-site medical service, accepting intrinsic risk-taking behavior. This may include on-site drug-checking, providing reliable information on drug content with associated education. Luther M , Gardiner F , Lenson S , Caldicott D , Harris R , Sabet R , Malloy M , Perkins J . An effective risk minimization strategy applied to an outdoor music festival: a multi-agency approach. Prehosp Disaster Med. 2018;33(2):220-224.