British Journal of Clinical Pharmacology · 2013 · 92 citations · 14 references
PharmacyPharmacokineticsPharmacologyBioavailabilityClinical PharmacologyPharmacokinetic ModelingBioavailability AnalysisCommunity-acquired Infection TreatmentPharmacokinetics In Critical IllnessPneumonia PharmacotherapyPulmonary PharmacokineticsArea Under The Concentration - Time CurveCommunity-acquired Pneumonia TreatmentGastric Emptying TimeIntravenous Corticosteroid TherapyOral Corticosteroid TherapyOral Corticosteroid UseSystemic Exposure AssessmentSystemic Exposure Measurement
AIM: The use of corticosteroids as adjunctive therapy might be effective in patients with community-acquired pneumonia (CAP). Oral administration of dexamethasone is a practical and safer alternative to the intravenous route. Since patients hospitalized with pneumonia might have delayed gastric emptying, this study explored systemic exposure in terms of area under the concentration-time curve (AUC) of oral dexamethasone in patients hospitalized with CAP. METHODS: In this randomized, open label study, 30 patients admitted with CAP were randomized to receive either 4 mg intravenous or 6 mg oral dexamethasone for 4 consecutive days. Serial blood samples were obtained before and after drug administration. RESULTS: Median AUC to infinity was 626 μg l(-1) h (IQR 401-1161) for the intravenous group and 774 μg l(-1) h (IQR 618-1146) for the oral group. The AUC ratio of 6 mg oral and 4 mg intravenous dexamethasone was 1.22 (95% confidence interval (CI) 0.81, 1.82), which represents a bioavailability of 81% (95% CI 54, 121) after correction for differences in dexamethasone dose. CONCLUSIONS: Bioavailability of oral dexamethasone in patients hospitalized with pneumonia is sufficient. This makes oral dexamethasone an appropriate alternative for intravenous administration in these patients.
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