Validation of a simple HPLC-UV method for rifampicin determination in plasma: Application to the study of rifampicin arteriovenous concentration gradient


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Abstract

HIGHLIGHTSRifampicin exposure is usually estimated from its concentration in the venous blood.A simple HPLC-UV method for rifampicin determination in plasma was validated.Rifampicin arterial and venous plasma kinetics were compared in baboons.Arterial concentrations are higher than in venous plasma in the distribution phase.Arteriovenous concentration equilibrium is obtained 6 h after rifampicin infusion.In clinical practice, rifampicin exposure is estimated from its concentration in venous blood samples. In this study, we hypothesized that differences in rifampicin concentration may exist between arterial and venous plasma.An HPLC-UV method for determining rifampicin concentration in plasma using rifapentine as an internal standard was validated. The method, which requires a simple protein precipitation procedure as sample preparation, was performed to compare venous and arterial plasma kinetics after a single therapeutic dose of rifampicin (8.6 mg/kg i.v, infused over 30 min) in baboons (n = 3).The method was linear from 0.1 to 40 μg mL−1 and all validation parameters fulfilled the international requirements. In baboons, rifampicin concentration in arterial plasma was higher than in venous plasma. Arterial Cmax was 2.1 ± 0.2 fold higher than venous Cmax. The area under the curve (AUC) from 0 to 120 min was ˜80% higher in arterial plasma, indicating a significant arteriovenous concentration gradient in early rifampicin pharmacokinetics. Arterial and venous plasma concentrations obtained 6 h after rifampicin injection were not different.An important arteriovenous equilibration delay for rifampicin pharmacokinetics is reported. Determination in venous plasma concentrations may considerably underestimate rifampicin exposure to organs during the distribution phase.

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