A study of the relative bioavailability of cysteamine hydrochloride, cysteamine bitartrate and phosphocysteamine in healthy adult male volunteers. (1/3)

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, infinity) (geometric mean and s.d. in micromol l(-1) h: 169+/-51, 158+/-46, 173+/-49 with cysteamine hydrochloride, phosphocysteamine and cysteamine bitartrate respectively), Cmax (geometric mean and s.d. in micromol 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 [75.6-105.81 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<0.001). The nature of the salt tested did not influence vomiting. CONCLUSIONS: While none of the three forms of cysteamine tested has a clear advantage over the others in terms of pharmacokinetics and tolerance profile, this should now however be addressed in patients treated for cystinosis during repeat administrations.  (+info)

Effects of oral phosphocysteamine and rectal cysteamine in cystinosis. (2/3)

Diurnal variation in leucocyte cystine and the effects of equimolar single doses of oral phosphocysteamine and rectal cysteamine were studied in eight patients with cystinosis, aged 1.8-16.5 years. No significant diurnal variation in leucocyte cystine was found. Absorption of cysteamine was reduced after rectal administration compared with the oral dose: mean (SD) peak concentration 17.2 (6.3) mumol/l v 36.4 (5.5) mumol/l at 40 min and mean (SD) area under the curve 22.3 (14.3) v 59.4 (33.1) mumol/h/l. Oral phosphocysteamine significantly reduced the mean (SD) leucocyte cystine from 8.09 (0.47) to 3.26 (1.48) nmol 1/2 cystine/mg protein at three hours. At 12 hours the mean leucocyte cystine was significantly lower than the pretreatment concentration. Rectal cysteamine did not significantly reduce the mean leucocyte cystine concentration. In conclusion, phosphocysteamine suspension may be administered every 12 hours. Rectal cysteamine administration is feasible but higher doses are required before efficacy can be judged.  (+info)

Combination small molecule PPT1 mimetic and CNS-directed gene therapy as a treatment for infantile neuronal ceroid lipofuscinosis. (3/3)