Correlation between plasma diphenhydramine level and sedative and antihistamine effects

Area of Science:

• Pharmacology
• Clinical Pharmacology

Background:

• Diphenhydramine is a common antihistamine with known sedative properties.
• Understanding the pharmacokinetic and pharmacodynamic relationship is crucial for optimizing its use.

Purpose of the Study:

• To assess the sedative and antihistamine effects of diphenhydramine in relation to plasma concentration.
• To determine the pharmacokinetic parameters of diphenhydramine after intravenous and oral administration.
• To identify a potential therapeutic window for antihistamine effect without significant sedation.

Main Methods:

• A randomized, placebo-controlled, three-way crossover study was conducted in 6 healthy volunteers.
• Diphenhydramine was administered intravenously (50 mg) and orally (50 mg), with placebo on separate occasions.
• Plasma concentrations, sedative effects, and antihistamine effects (histamine-induced wheal reduction) were measured.

Main Results:

• Diphenhydramine plasma elimination half-life (t1/2) ranged from 3.0 to 4.3 hr, volume of distribution from 188 to 336 L, and clearance from 637 to 1,014 ml/min.
• Systemic bioavailability of oral diphenhydramine varied between 0.26 and 0.60.
• Sedative effects were significant for only 3 hours post-intravenous administration, whereas antihistamine effects persisted for at least 8 hours.
• A positive correlation was observed between plasma diphenhydramine levels and both sedative and antihistamine effects, with considerable inter-individual variability.
• A plasma concentration range of 25-50 ng/ml appears to offer significant antihistamine effects with minimal sedation.

Conclusions:

• Diphenhydramine exhibits a prolonged antihistamine effect compared to its sedative effect.
• A specific plasma concentration range may allow for effective allergy management without significant drowsiness.
• Inter-individual variability in response necessitates careful dosing and monitoring.