A study of the relative bioavailability of cysteamine hydrochloride, cysteamine bitartrate and phosphocysteamine in healthy adult male volunteers

Aims Cysteamine, the only drug available for the treatment of cystinosis in paediatric patients, is available as the hydrochloride, the bitartrate and as sodium phosphocysteamine salts. It has been suggested that cysteamine bitartrate and phosphocysteamine are better tolerated and may have a better bioavailability than cysteamine hydrochloride. This has, however, never been demonstrated. Methods We compared the pharmacokinetics and tolerance of these three formulations of cysteamine in 18 healthy adult male volunteers in a double‐blind, latin‐square, three‐period, single oral dose cross‐over relative bioavailability study. Results No statistical difference was found between relative bioavailabilities, AUC (0, ∞) (geometric mean and s.d. in μmol l−1h: 169±51, 158±46, 173±49 with cysteamine hydrochloride, phosphocysteamine and cysteamine bitartrate respectively), Cmax (geometric mean and s.d. in μmol l−1: 66±25.5, 59±12, 63±20) and tmax (median and range in h: 0.88 (0.25–2), 1.25 (0.25–2), 0.88 (0.25–2)) with each of the three forms of cysteamine tested. Bioequivalence statistics (90% confidence intervals) showed non equivalence of Cmax of cysteamine base as the only non equivalence of pharmacokinetics between the three formulations: 90% CI for Cmax relative ratios to cysteamine hydrochloride were [75.6–105.8] for phosphocysteamine and [74.2–124.2] for cysteamine bitartrate. The only significant adverse event was vomiting whose frequency was inversely correlated with body weight (Spearman’s r=−0.76, P