Levofloxacin pharmacokinetics in saliva as measured by a mobile microvolume UV spectrophotometer among people treated for rifampicin-resistant TB in Tanzania
| Autor: | Happiness C Mvungi, Jan-Willem C. Alffenaar, Sagal Y Mohamed, Erwin M Jongedijk, Daan J Touw, Scott K. Heysell, Stellah G. Mpagama, Peter M. Mbelele, Margaretha Sariko, Suzanne Stroup, Claudia A J van Winkel, Prakruti Rao |
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| Přispěvatelé: | Pharmaceutical Analysis, Critical care, Anesthesiology, Peri-operative and Emergency medicine (CAPE), Medicinal Chemistry and Bioanalysis (MCB), Biopharmaceuticals, Discovery, Design and Delivery (BDDD) |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Microbiology (medical)
Saliva medicine.medical_specialty Rifampicin resistant Human immunodeficiency virus (HIV) Antitubercular Agents Levofloxacin medicine.disease_cause TUBERCULOSIS High-performance liquid chromatography Gastroenterology Tanzania Pharmacokinetics Internal medicine medicine AcademicSubjects/MED00740 Humans Pharmacology (medical) Dosing Original Research Pharmacology business.industry Bayes Theorem Regimen Infectious Diseases AcademicSubjects/MED00290 Spectrophotometry Female Rifampin business AcademicSubjects/MED00230 medicine.drug |
| Zdroj: | Journal of Antimicrobial Chemotherapy, 76(6), 1547-1552. Oxford University Press Journal of Antimicrobial Chemotherapy |
| ISSN: | 0305-7453 |
| Popis: | Background Early detection and correction of low fluoroquinolone exposure may improve treatment of MDR-TB. Objectives To explore a recently developed portable, battery-powered, UV spectrophotometer for measuring levofloxacin in saliva of people treated for MDR-TB. Methods Patients treated with levofloxacin as part of a regimen for MDR-TB in Northern Tanzania had serum and saliva collected concurrently at 1 and 4 h after 2 weeks of observed levofloxacin administration. Saliva levofloxacin concentrations were quantified in the field via spectrophotometry, while serum was analysed at a regional laboratory using HPLC. A Bayesian population pharmacokinetics model was used to estimate the area under the concentration–time curve (AUC0–24). Subtarget exposures of levofloxacin were defined by serum AUC0–24 Results Among 45 patients, 11 (25.6%) were women and 16 (37.2%) were living with HIV. Median AUC0–24 in serum was 140 (IQR = 102.4–179.09) mg·h/L and median AUC0–24 in saliva was 97.10 (IQR = 74.80–121.10) mg·h/L. A positive linear correlation was observed with serum and saliva AUC0–24, and a receiver operating characteristic curve constructed to detect serum AUC0–24 below 80 mg·h/L demonstrated excellent prediction [AUC 0.80 (95% CI = 0.62–0.94)]. Utilizing a saliva AUC0–24 cut-off of 91.6 mg·h/L, the assay was 88.9% sensitive and 69.4% specific in detecting subtarget serum AUC0–24 values, including identifying eight of nine patients below target. Conclusions Portable UV spectrophotometry as a point-of-care screen for subtarget levofloxacin exposure was feasible. Use for triage to other investigation or personalized dosing strategy should be tested in a randomized study. |
| Databáze: | OpenAIRE |
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