Exploration of the pharmacokinetics of clindamycin and its metabolites in special patients: from bioanalysis to clinical relevance

When antibiotics are administered to special patients like pregnant women as prophylactic drugs during fetal surgery, as well as during orthopedic and trauma surgery infections, the metabolism and pharmacokinetics are often different from reference patients without these specific characteristics. Furthermore, drug-drug interactions (DDIs) can also be relevant in the event of co-administration of drugs. The research of this dissertation will focus on the metabolism and pharmacokinetics of clindamycin and its active metabolites in these special patients and on the effects of simultaneous administration of clindamycin and CYP3A4-inducers (rifampicin, flucloxacillin). The bioanalytical part of the work will involve the development and validation of different LC-MS/MS assays for the quantification of clindamycin and its metabolites as well as for the co-administered antibiotics. The methods will be applied to clinical samples from these special patients to measure exposure. The drug and metabolite profiles will be evaluated by population pharmacokinetic modeling of the concentrations obtained from the clinical samples. This work will contribute to describe and quantify the potential relevance of CLI’s metabolites and aforementioned DDIs, as these findings hold the feasibility to guide clinical practice in specific subgroups (pregnant women, trauma) or individual cases (DDI).