Bioavailability analysis of chlorpromazine in humans from pupilometric data

Area of Science:

• Pharmacology
• Ophthalmology
• Clinical Pharmacology

Background:

• Chlorpromazine is an antipsychotic medication with known effects on pupil size.
• Assessing the bioavailability of chlorpromazine, particularly at low doses, presents challenges with traditional methods.

Purpose of the Study:

• To investigate the dose-response relationship of chlorpromazine's miotic effect.
• To evaluate pupilometry as a method for determining chlorpromazine bioavailability.
• To compare the potency of intravenous versus oral chlorpromazine administration.

Main Methods:

• Studied time variation of miotic response intensity in 16 human subjects over 6-8 hours post-dosing.
• Administered various oral liquid and intravenous doses of chlorpromazine.
• Utilized pupilometry to measure miotic response and construct dose-effect curves.

Main Results:

• Intravenous chlorpromazine infusion was approximately 11 times more potent than oral syrup in eliciting miotic response.
• Miotic activity demonstrated dose sensitivity, with approximately linear dose-effect curves for both administration routes.
• Pupilometry proved to be a sensitive, reliable, and rapid method for detecting differences in chlorpromazine bioavailability.

Conclusions:

• Pupilometry is a valuable tool for comparative bioavailability studies of chlorpromazine, especially for low oral doses where direct assays are insufficient.
• The method allows for the detection of significant bioavailability differences between oral dosage forms at low therapeutic levels.