Levofloxacin pharmacokinetics in saliva as measured by a mobile microvolume UV spectrophotometer among people treated for rifampicin-resistant TB in Tanzania

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 (AUC(0–24)). Subtarget exposures of levofloxacin were defined by serum AUC(0–24) <80 mg·h/L. The study was registered at Clinicaltrials.gov with clinical trial identifier NCT04124055. RESULTS: Among 45 patients, 11 (25.6%) were women and 16 (37.2%) were living with HIV. Median AUC(0–24) in serum was 140 (IQR = 102.4–179.09) mg·h/L and median AUC(0–24) in saliva was 97.10 (IQR = 74.80–121.10) mg·h/L. A positive linear correlation was observed with serum and saliva AUC(0–24), and a receiver operating characteristic curve constructed to detect serum AUC(0–24) below 80 mg·h/L demonstrated excellent prediction [AUC 0.80 (95% CI = 0.62–0.94)]. Utilizing a saliva AUC(0–24) cut-off of 91.6 mg·h/L, the assay was 88.9% sensitive and 69.4% specific in detecting subtarget serum AUC(0–24) 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.