title: A Novel Study Using Accelerated Mass Spectrometry to Evaluate the Pharmacokinetics of Total (14)C AL-8309 (Tandospirone) Following Topical Ocular Administration in Healthy Male Subjects.
abstract: The primary objective of this study is to characterize the pharmacokinetics of total (14)C concentrations following bilateral, topical ocular drops of (14)C-AL-8309B labeled either at the pyrimidyl ring (cohort A) position or at the imido-carbonyl ring (cohort B) position twice daily from day 1 through day 6 and once in the morning of day 7 in 16 healthy male subjects (8 per cohort). Each drop (approximately 24 μL) of (14)C-AL-8309B 1.75% ophthalmic solution (equivalent to 420 μg-equiv AL-8309) contained approximately 500 nCi of (14)C-AL-8309. AL-8309 systemic absorption was relatively slow; the time of maximum observed plasma concentrations ranged from 0.25 to 3 hours. Moderate accumulation (1.48- to 1.86-fold) was observed in the mean systemic total (14)C plasma concentrations at steady state (day 7) compared with single dose (day 1). The mean total (14)C eliminated was 3.5-fold and 3.7-fold greater in the urine than the feces for cohort A and cohort B, indicating that (14)C-AL-8309 is primarily excreted through renal elimination. Single and multiple topical doses of AL-8309B were found to be safe and well-tolerated in healthy subjects. This is the first reported use of accelerator mass spectrometry technology with a topically applied ophthalmic product.
authors.affiliation: Alcon Labs, Fort Worth, Texas, USA.
authors.forename: Ganesh R
authors.initials: GR
authors.lastname: Iyer
authors.affiliation: Alcon Labs, Fort Worth, Texas, USA.
authors.forename: Yamini
authors.initials: Y
authors.lastname: Patel
authors.affiliation: Alcon Labs, Fort Worth, Texas, USA.
authors.forename: Nathan S
authors.initials: NS
authors.lastname: Teuscher
keywords: 5HT1A; AL‐8309 (Tandospirone); accelerator mass spectrometry technology; geography atrophy; low radioactive dose; retina; serotonin