Main objective- To study the influence of the polymorphisms of nuclear receptor proteins pregnane X receptor (PXR), Liver X receptor alpha (LXRα), and Cytochrome P450 (CYP450) on the clindamycin clearance during clindamycin/rifampin combination therapy. Secondary objectives To study the influence of these polymorphisms on clindamycin clearance, before combination therapy with rifampin (clindamycin monotherapy) To study the influence of these polymorphisms on CYP450 activity before combination therapy with rifampin (clindamycin monotherapy) To study the influence of these polymorphisms on the increase of CYP450 activity after clindamycin/rifampin combination therapy To study the difference between the expected and observed clindamycin serum concentrations after dosage adjustment, in patients with clindamycin dosage adjustment after combination therapy with rifampin
Eligible patients will be informed on the study during their hospitalisation in the unit for the treatment of bone and joint infection by the medical doctor. If they agree to participate in the study, the following samples will be performed : * After at least 24 hours of clindamycin therapy and before combination therapy with rifampin: * 1 urine sample (5 mL) for CYP 450 activity phenotyping * 1 blood sample (5 mL on ethylenediaminetetraacetic acid (EDTA) tubes) for measuring clindamycin serum concentration and genotyping * After ten days of clindamycin-rifampin combination therapy: * 1 urine sample (5 mL) for CYP 450 activity phenotyping * 1 blood sample (5 mL on EDTA tubes) for measuring clindamycin serum concentration and genotyping
Study Type
OBSERVATIONAL
Enrollment
84
Groupe Hospitalier Diaconesses Croix Saint Simon
Paris, France
Genetic polymorphism of PXR, LXRalpha, CYP450 on clindamycin clearance with clindamycin/rifampin combination therapy
Impact of PXR, LXRα, CYP 450 3A4/A5 polymorphism on clindamycin clearance after combination clindamycin-rifampin therapy will be analyzed by studying the association of these polymorphisms and clindamycin serum concentrations.
Time frame: 10 days after onset of clindamycin/rifampin combination therapy
Genetic polymorphism of PXR, LXRalpha, CYP450 on clindamycin clearance before combination therapy with rifampin (clindamycin monotherapy)
Impact of PXR, LXRα, CYP 450 3A4/A5 polymorphism on clindamycin clearance before rifampin therapy will be analyzed by studying the association of these polymorphisms and clindamycin serum concentrations.
Time frame: One to four days after onset of clindamycin therapy and before starting rifampin therapy
Genetic polymorphism of PXR, LXRalpha, CYP450 on the increase of CYP 3A4 activity before combination therapy with rifampin
Impact of PXR, LXRα, CYP 450 3A4/A5 polymorphism on CYP 450 3A activity before combination therapy with rifampin will be analyzed by studying the association of these polymorphisms and clindamycin serum concentrations.
Time frame: One to four days after onset of clindamycin therapy and before starting rifampin therapy
Genetic polymorphism of PXR, LXRalpha, CYP450 on the increase of CYP 3A4 activity after clindamycin/rifampin combination therapy
Impact of PXR, LXRα, CYP 450 3A4/A5 polymorphism on CYP 450 3A activity after combination with rifampin therapy will be analyzed by studying the association of these polymorphisms and clindamycin serum concentrations.
Time frame: 10 days after onset of clindamycin/rifampin combination therapy
Difference between expected and observed clindamycine serum concentration after dosage adjustment, in patients after combination therapy with clindamycin and rifampin,.
The gap between the predicted and observed clindamycin serum concentrations will be quantified by MPE (Mean Prediction Errors) and RMSE (Root Mean Square Prediction Errors). Dosage adjustment will be considered predictive of the concentration if MPE and RMSE are \< 20 %.
Time frame: 10 days after onset of clindamycin/rifampin combination therapy
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