Increased Prevalence of Abnormalities in Glucocorticoid Pharmacokinetics Among Clinically Steroid Resistant Obese Asthmatics

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RATIONALE: Abnormal glucocorticoid (GC) pharmacokinetics (PK) can affect clinical response to GCs. How obesity influences GC PK in asthma is unclear.

METHODS: A modified prednisone PK study with blood samples obtained at baseline, 2 and 6 h post oral prednisone dose (40 mg/1.73m2 of body surface area) was performed in 17 adult steroid resistant (SR) asthmatics (based on ≤12% improvement in FEV1% after 1 week of prednisone 40 mg daily) using high performance liquid chromatography. Prednisolone concentration at 2 h was classified as abnormal if <400 ng/ml was detected. Prednisolone clearance (estimated log clearance= 2.66 + [6 h post dose concentration][-0.00167]) above 255 ml/min/1.73m2 was considered rapid.

RESULTS: Patients with BMI > 30 had significantly lower baseline FEV1% (Mean ± SD 61.5 ± 10.7% vs 74.4 ± 9.8%, p30 had low 2 h prednisolone concentrations and/or rapid clearance, whereas only 3 (1 with BMI < 25, 2 with BMI 25-30) out of 11 in the BMI group < 30 had such abnormalities (p30 vs BMI30 group. Hence, the estimated clearance was greater in patients with BMI > 30 (272.1 ± 34.8 vs 210.4 ± 43.4 ml/min/1.73m2, p = 0.01).

CONCLUSIONS: The higher prevalence of PK abnormalities among obese SR asthmatics may contribute to their suboptimal response to steroid treatment. The specific PK abnormalities (e.g. absorption, interconversion, or clearance) and the relationship to obesity require further investigation.