Evaluation of saliva as a potential alternative sampling matrix for therapeutic drug monitoring of levofloxacin in MDR-TB patientsGhimire, S., Maharjan, B., Jongedijk, E. M., Kosterink, J. G. W., Ghimire, G. R., Touw, D. J., van der Werf, T. S., Shrestha, B. & Alffenaar, J-W. C., 19-Feb-2019, In : Antimicrobial Agents and Chemotherapy. 26 p.
Research output: Contribution to journal › Article › Academic › peer-review
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Saliva may be a useful alternative matrix for monitoring levofloxacin concentrations in multi-drug resistant TB patients. The objectives of this study were: a) to evaluate the correlation between plasma and salivary Lfx concentrations in MDR-TB patients; and b) to gauge the possibility of using saliva as an alternative sampling matrix for therapeutic drug monitoring of Lfx in TB endemic areas. This was a prospective pharmacokinetic study that enrolled MDR-TB patients receiving levofloxacin (Lfx; 750-1000mg once daily dosing) under standardized treatment regimen in Nepal. Paired blood and saliva samples were collected at steady state. Lfx concentrations were quantified using liquid chromatography- tandem mass spectrometry. Pharmacokinetic parameters were calculated using non-compartmental kinetics. Lfx drug exposure was evaluated in 23 MDR-TB patients. During the first month, the median (IQR) area under the concentration-time curve (AUC0-24) was 67.09 (53.93-98.37) mg*h/L in saliva and 99.91 (76.80-129.70) mg*h/L in plasma, and the saliva plasma (S/P) ratio was 0.69 (0.53-0.99). Similarly, during the second month, the median (IQR) AUC0-24 was 75.63 (61.45-125.5) mg*h/L in saliva and 102.7 (84.46-131.9) mg*h/L in plasma with a S/P ratio of 0.73 (0.66-1.18). Furthermore, large inter-and intra-individual variabilities in Lfx concentrations were observed. This study could not demonstrate a strong correlation between plasma and saliva Lfx levels. Despite a good Lfx penetration in saliva, the variability in individual saliva-to-plasma ratios limits the use of saliva as a valid substitute for plasma. Nevertheless, saliva could be useful in semi-quantitatively predicting Lfx plasma levels.
|Number of pages||26|
|Journal||Antimicrobial Agents and Chemotherapy|
|Publication status||E-pub ahead of print - 19-Feb-2019|