Pharmacokinetic Studies of Cysteamine Bitartrate Delayed-Release.

Abstract

A twice-daily microsphere formulation of cysteamine bitartrate has been developed for cystinosis and other potential applications. To date, there are no published pharmacokinetic data for cysteamine bitartrate delayed-release in healthy adults. Three randomized open-label, crossover studies to determine the effects of fasting, high fat, and carbohydrate meals on the bioavailability of cysteamine bitartrate delayed-release (600 mg) administered in capsule or sprinkle form to healthy adults. Adverse events were monitored. Fifty-eight adults were studied. Cysteamine absorption (AUC0-24 hours ) was the same for capsule and sprinkle forms during all meal/fasting states. The AUC0-24 hours for capsules while fasted, 30 and 120 minutes before a carbohydrate meal and during a high fat meal were 6,313 ± 329, 4,616 ± 878, 6,691 ± 669, 2,572 ± 295 minutes × µM, respectively, and the mean Cmax values were 29.4 ± 1.7, 20.7 ± 4.9, 31.6 ± 3.0, and 10.9 ± 1.7 µM, respectively. The mean Tmax following fasting and high fat meal were about 3 and 6 hours, respectively. Minor transient GI adverse events occurred. Cysteamine bitartrate delayed-release capsule and sprinkle forms are bioequivalent and optimal absorption occurs during fasting state. High fat diet reduces drug absorption, increases the Tmax and should be avoided at the time of drug ingestion. Cysteamine bitartrate delayed-release (RP103) is best ingested >30 minutes before a carbohydrate-rich meal.