Detectable prednisolone is delayed in pericardial fluid, compared with plasma of patients with tuberculous pericarditis: A pilot study

BACKGROUND: In patients with tuberculous pericarditis [TBP] adjunctive prednisolone reduces the incidence of constrictive pericarditis. It is unknown whether prednisolone permeates adequately into pericardial fluid. Drug measurements in pericardial fluid require invasive procedures, and thus less invasive methods are needed to perform full pharmacokinetic characterization of prednisolone in large numbers of patients. We sought to evaluate the relationship between prednisolone concentrations in pericardial fluid, plasma, and saliva. METHODS: Plasma, pericardial fluid, and saliva samples were collected at 7 time points from TBP patients randomized to 120 mg prednisolone or placebo. Compartmental pharmacokinetic parameters, peak concentration [C(max)], and 0–24 h area under the concentration-time curve [AUC(0–24)] were identified in plasma, saliva and pericardial fluid. RESULTS: There were five patients each in the prednisolone and placebo groups. Prednisolone concentrations were best described using a one compartment model. The absorption half-life into plasma was 1 h, while that into pericardial fluid was 9.4 h, which led to a median time-to-maximum concentration in plasma of 2.0 h versus 5.0 h in pericardial fluid [p = 0.048]. The concentration-time profiles in pericardial fluid versus plasma exhibited system hysteresis. The pericardial fluid-to-plasma C(max) peak concentration ratio was 0.28 (p = 0.032), while the AUC(0–24) ratio was 0.793. The concentration-time profiles in saliva had a similar shape to those in plasma, but the saliva-to-plasma C(max) was 0.59 [p = 0.032]. CONCLUSION: The prednisolone AUC(0–24) achieved in pericardial fluid approximates that in plasma, but the C(max) is low due to delayed absorption. Saliva can be used as surrogate sampling site for pericardial fluid prednisolone.