Key result
In patients with tuberculous pericarditis, prednisolone absorption into pericardial fluid was delayed compared to plasma, with a median time-to-maximum concentration of 5.0 h vs 2.0 h (p=0.048).
Why the study?
It is unknown whether adjunctive prednisolone permeates adequately into pericardial fluid in tuberculous pericarditis, and less invasive pharmacokinetic methods are needed.
Does prednisolone 120 mg permeate adequately into pericardial fluid compared to plasma in patients with tuberculous pericarditis?
RCT (n=10)
randomized
Does prednisolone 120 mg permeate adequately into pericardial fluid compared to plasma in patients with tuberculous pericarditis?
Prednisolone absorption into pericardial fluid is delayed compared to plasma, but overall exposure is similar, and saliva may be used as a surrogate sampling site for pericardial fluid prednisolone.
Supports standard dosing despite delayed absorption; extends PK data and validates saliva as pericardial surrogate.
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. 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 [Cmax], and 0–24 h area under the concentration-time curve [AUC0–24] were identified in plasma, saliva and pericardial fluid. 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 Cmax peak concentration ratio was 0.28 (p = 0.032), while the AUC0–24 ratio was 0.793. The concentration-time profiles in saliva had a similar shape to those in plasma, but the saliva-to-plasma Cmax was 0.59 [p = 0.032]. The prednisolone AUC0–24 achieved in pericardial fluid approximates that in plasma, but the Cmax is low due to delayed absorption. Saliva can be used as surrogate sampling site for pericardial fluid prednisolone.
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Shenje et al. (2019) conducted an RCT in Tuberculous pericarditis (n=10). Prednisolone vs. Placebo was evaluated on Median time-to-maximum concentration in pericardial fluid versus plasma (p=0.048). In patients with tuberculous pericarditis, prednisolone absorption into pericardial fluid was delayed compared to plasma, with a median time-to-maximum concentration of 5.0 h vs 2.0 h (p=0.048).
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