Study of the pharmacokinetics of levofloxacin when combined with st. John’s wort preparations in healthy volunteers and in patients with lower respiratory tract infection

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Abstract

In patients with pneumonia and concomitant diseases, the administration of antimicrobial agents together with other medications accompanied by the risk of side effects and drug-drug interactions. We studied the pharmacokinetics (PK) of levofloxacin when combined with a herbal preparation (common St. John’s wort extract) in healthy volunteers and in patients with community-acquired pneumonia on the days 1 and 5 of the drugs intake. Individual differences in the average concentrations (AUC analog) of the antibiotic before and after the course of administration of the St. John’s wort extract within each group were quite significant; however, the group-average differences were statistically insignificant. Intergroup differences in PK with St. John’s wort intake were also statistically insignificant. To search for factors that make a significant contribution to the variations observed in PK indices, we used a statistical multivariate analysis of variance which included factors such as gender, age, body mass index, smoking history, and cardiovascular system parameters. We found that smoking only and, to a lesser extent, the patient’s gender had an effect on levofloxacin PK, while the intake of St. John’s wort completely eliminated this effect. Other factors played an insignificant role in the antibiotic PK regardless of the St. John’s wort administration.

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About the authors

Liudmila M. Krasnyk

Scientific Centre for Expert Evaluation of Medicinal Products

Author for correspondence.
Email: krasnyh@expmed.ru
ORCID iD: 0000-0003-3650-6014

candidate of medical sciences “Scientific Centre for Expert Evaluation of Medicinal Products”; senior analyst of the Department of clinical pharmacokinetics “Clinical Pharmacology Center”

Russian Federation, Moscow

Olga A. Goroshko

Scientific Centre for Expert Evaluation of Medicinal Products

Email: olga_goroshko@mail.ru
ORCID iD: 0000-0003-0448-3612

MD, PhD

Russian Federation, Moscow

Dmitry V. Tsyganko

I.V.Davydovsky State Clinical Hospital DZM

Email: riverdrinkins@mail.ru
Russian Federation, Moscow

Nadezhda G. Berdnicova

I.V.Davydovsky State Clinical Hospital DZM; I.M. Sechenov First Moscow State Medical University (Sechenov University)

Email: berdnad@mail.ru
ORCID iD: 0000-0002-2036-7403

MD, PhD

Russian Federation, Moscow

Viktoria G. Krasnyanskaya

Scientific Centre for Expert Evaluation of Medicinal Products

Email: krasnyanskaya65@mail.ru
ORCID iD: 0000-0001-7604-8172
Russian Federation, Moscow

Valeriy A. Menshov

N.M. Emanuel Institute of Biochemical Physics

Email: vinoman66@mail.ru
ORCID iD: 0000-0002-9183-8292

MD, PhD

Russian Federation, Moscow

References

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  8. Hall S.D., Wang Z., Huang S.M., Hamman M.A., Vasavada N., Adigun A.Q. et al. The interaction between St John’s wort and an oral contraceptive. Clin Pharmacol Ther. 2003;74(6):525-35. doi: 10.1016/j.clpt.2003.08.009.
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Supplementary files

Supplementary Files
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1. Fig. 1. Individual values of the concentration of levofloxacin in patients receiving SEZP (1st day of the study). P1-P5 - patient code numbers.

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2. Fig. 2. Individual PK levels of levofloxacin in patients treated with SESP (5th day of the study). P1-P5 - patient code numbers.

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3. Fig. 3. Average concentrations of levofloxacin in patients with community-acquired pneumonia treated with SESP.

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4. Fig. 4. Average concentrations of levofloxacin in patients with CAP without additional intake of SEZP.

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5. Fig. 5. Average concentrations of a single dose of levofloxacin 500 mg in healthy volunteers taking SEZP.

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6. Fig. 6. Mean group changes in mean daily concentrations of levofloxacin with or without SEZP (data are presented as mean and standard deviations, Mean ± SD).

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7. Fig. 7. Visual analysis of the influence of the most significant factors and interfactor interactions.

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