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

Sagal Mohamed, Happiness C Mvungi, Margaretha Sariko, Prakruti Rao, Peter Mbelele, Erwin M Jongedijk, Claudia A J van Winkel, Daan J Touw, Suzanne Stroup, Jan-Willem C Alffenaar, Stellah Mpagama, Scott K Heysell, Sagal Mohamed, Happiness C Mvungi, Margaretha Sariko, Prakruti Rao, Peter Mbelele, Erwin M Jongedijk, Claudia A J van Winkel, Daan J Touw, Suzanne Stroup, Jan-Willem C Alffenaar, Stellah Mpagama, Scott K Heysell

Abstract

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 <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 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.

© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy.

Figures

Figure 1.
Figure 1.
Passing–Bablok analysis of serum and saliva AUC0–24. The solid black line represents the fitted Passing–Bablok line and the solid grey line represents the line of identity.
Figure 2.
Figure 2.
ROC curve to identify serum AUC0–24 below 80 mg·h/L.

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Source: PubMed

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