A 30-years Review on Pharmacokinetics of Antibiotics: Is the Right Time for Pharmacogenetics?
Lorena Baietto, Silvia Corcione, Giovanni Pacini, Giovanni Di Perri, Antonio D’Avolio and Francesco Giuseppe De Rosa
Affiliation: Department of Medical Sciences, University of Turin, Infectious Diseases at Amedeo di Savoia Hospital, Corso Svizzera 164, 10149. Turin, Italy.
Keywords: Metabolism, pharmacology, pharmacogenomic, single nucleotide polymorphism (SNP), tailored therapy, therapeutic drug monitoring
(TDM), transporter, treatment.
Drug bioavailability may vary greatly amongst individuals, affecting both efficacy and toxicity: in humans, genetic variations
account for a relevant proportion of such variability. In the last decade the use of pharmacogenetics in clinical practice, as a tool to individualize
treatment, has shown a different degree of diffusion in various clinical fields.
In the field of infectious diseases, several studies identified a great number of associations between host genetic polymorphisms and responses
to antiretroviral therapy. For example, in patients treated with abacavir the screening for HLA-B*5701 before starting treatment
is routine clinical practice and standard of care for all patients; efavirenz plasma levels are influenced by single nucleotide polymorphism
(SNP) CYP2B6-516G>T (rs3745274). Regarding antibiotics, many studies investigated drug transporters involved in antibiotic bioavailability,
especially for fluoroquinolones, cephalosporins, and antituberculars. To date, few data are available about pharmacogenetics of
recently developed antibiotics such as tigecycline, daptomycin or linezolid. Considering the effect of SNPs in gene coding for proteins
involved in antibiotics bioavailability, few data have been published.
Increasing knowledge in the field of antibiotic pharmacogenetics could be useful to explain the high drug inter-patients variability and to
individualize therapy. In this paper we reported an overview of pharmacokinetics, pharmacodynamics, and pharmacogenetics of antibiotics
to underline the importance of an integrated approach in choosing the right dosage in clinical practice.
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