Comparative pharmacokinetics of levofloxacin in the saliva and blood plasma of patients with pneumonia

BACKGROUND: Levofloxacin concentrations do not always reach desired levels when administered at a standard dose; therefore, measuring levofloxacin levels in the blood plasma or other alternative matrices, such as the saliva, can help clinicians make informed decisions concerning the dosage and mode of administration. Saliva, as an object of research, is of particular interest due to the simplicity and non-invasiveness of sampling for analysis.

AIM: This study aimed to determine the comparative pharmacokinetics of levofloxacin in the blood plasma and saliva of patients with community-acquired pneumonia (CAP) and assess the possibility of using saliva as an alternative sampling matrix in pharmacokinetic studies.

MATERIALS AND METHODS: Levofloxacin concentration in the blood plasma and saliva of patients with CAP and volunteers was determined using high-performance liquid chromatography on an Agilent 1200 liquid chromatography (Agilent, USA) with an ultraviolet detector. Sample preparation of bioassays was performed using protein precipitation. Patients and volunteers took 1 tablet (500 mg dose) of levofloxacin per os in the morning, on an empty stomach. Blood and saliva samples were taken at the initial blood sample and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 24 h after taking the drug. The pharmacokinetic parameters were determined, namely C_max as the peak concentration of the drug; Т_max as the time-to-peak concentration; AUC_0–t as the area under the pharmacokinetic curve in the range from 0 to the last experimental point on the curve; AUC_0–∞ as the total area under the pharmacokinetic curve from zero to infinity; t_1/2 as half-life period; MRT as mean residence time of the drug in the blood (h); Cl/F as clearance; and Vss/F as the total distribution volume.

RESULTS: The maximum blood plasma and saliva concentration of patients was reached 1 h after taking the drug and amounted to С_max=5.98±2.89 µg/ml and С_max=4.41±3.83 µg/ml, respectively. Additionally, the maximum concentrations in blood plasma and saliva were recorded 1 h after taking the drug as 5.52±3.07 μg/ml and 3.25±0.85 μg/ml, respectively, in healthy volunteers. The correlation coefficient (r) between the mean values of the levofloxacin concentrations in the blood plasma and the saliva of patients with CAP was 0.953 and that of healthy volunteers was 0.977.

DISCUSSION: Pharmacokinetic parameters were calculated based on blood plasma and saliva concentrations. Their comparative analysis revealed almost the same absorption rate from the gastrointestinal tract in patients and healthy volunteers. Correlation-regression analysis revealed a high correlation between the average values of C_max in saliva and plasma both in the patient (r=0.96) and healthy volunteer group (r=0.98).

CONCLUSIONS: With statistically significant differences in the areas under pharmacokinetic curves in blood plasma and saliva, the remaining pharmacokinetic parameters of saliva and blood plasma did not significantly differ between patients with CAP and healthy volunteers. A significant direct correlation was revealed between the mean concentration and pharmacokinetic parameters in saliva and blood plasma in both groups. The study demonstrated the possibility of using saliva as a biomaterial in the study of levofloxacin pharmacokinetics.