Bioavailability analysis of chlorpromazine in humans from pupilometric data

VF Smolen, HR Murdock and EJ Williams

Results of studying the time variation of the miotic response intensity for periods of 6 to 8 hours after dosing in up to 16 normal human subjects who received various oral liquid and intravenous doses of chlorpromazine are reported. Relative to oral liquid doses of chlorpromazine syrup, intravenous doses of the drug slowly infused over a consistent time interval of 30 minutes are approximately 11 times as potent in eliciting miotic response activity. Miotic activity was found to be quite dose sensitive as seen from the response vs. time profiles and the dose-effect curves constructed as plots of areas under the response curves and peak response intensities. The dose-effect curves are approximately linear for both intravenous and oral dosing over the majority of the dose ranges studied. Pupilometry is demonstrated as providing a highly sensitive, reliable, rapid and convenient method for detecting differences in both rates and extents of systemic chlorpromazine bioavailability after parenteral or oral dosing with chlorpromazine. Pupilometry allows comparative bioavailability studies to be readily completed for low oral doses, e.g., 10 mg/70 kg, which are not possible to perform even under the most ideal conditions, using the best direct assay techniques presently available. It is precisely at such low oral doses that bioavailability between oral dosage forms are most pronounced and the use of pupilometry has its greatest utility.

Volume 195, Issue 3, pp. 404-415, 12/01/1975
Copyright © 1975 by American Society for Pharmacology and Experimental Therapeutics