Glucocorticoids dosing in obese subjects: A systematic review

Area of Science:

• Pharmacology
• Clinical Pharmacy
• Endocrinology

Background:

• Glucocorticoids (GCs) are vital for managing inflammatory and autoimmune conditions.
• Obesity presents challenges in GC dosing due to altered drug metabolism and increased risk of side effects.
• Accurate dosing strategies are crucial for optimizing GC therapy in obese individuals.

Purpose of the Study:

• To review the determinants of GC pharmacokinetics (PK) in obese subjects.
• To analyze existing PK studies on GC dosing in obesity.
• To identify appropriate body size descriptors for GC dosage adjustments in obese patients.

Main Methods:

• Systematic literature search of PubMed using MeSH terms: "glucocorticoids", "pharmacokinetics", and "obesity" or "overweight".
• Inclusion criteria: English language, human studies, published up to August 31, 2017.
• Analysis of three published PK studies comparing dexamethasone, prednisolone, and methylprednisolone in obese and normal-weight subjects.

Main Results:

• GCs partially distribute into excess body weight, making total body weight (TBW) or excess body weight (EBW) inappropriate for dose adjustment.
• Adjusting doses by TBW or EBW may inappropriately increase initial plasma GC concentrations.
• Conflicting results exist regarding GC exposure and clearance based on the specific GC studied.

Conclusions:

• Current evidence indicates that adjusting GC doses by total body weight is likely inappropriate and potentially dangerous in obese patients.
• Further pharmacokinetic studies are essential to guide optimal GC dosing in obesity.
• Increased GC sensitivity in obese individuals, even with reduced exposure, highlights the need for cautious dosing strategies.