Background: Nephropathic cystinosis is an autosomal recessive disorder resulting in an impaired transport of\r\ncystine trough the lysosomal membrane causing an accumulation of free cystine in lysosomes. The only specific\r\ntreatment for nephropathic cystinosis is cysteamine bitartrate. This study was aimed to describe the relationship\r\nbetween cysteamine plasma concentrations and white blood cell cystine levels, and to simulate an optimized\r\nadministration scheme to improve the management of patients with cystinosis.\r\nMethods: Cysteamine and cystine concentrations were measured in 69 nephropathic cystinosis patients. A total of\r\n250 cysteamine plasma concentrations and 243 intracellular cystine concentrations were used to perform a\r\npopulation pharmacokinetic and pharmacodynamic analysis. An optimized administration scheme was simulated in\r\norder to maintain cystine levels below 1 nmol half-cystine/mg of protein and to investigate the possibility of\r\nadministrating the treatment less than 4 times a day (QID, recommended). The current dosing recommendations\r\nare 1.3 g/m2/day for less than 50 kg BW and 2 g/day thereafter; the maximum dose should not exceed 1.95 g/m2/\r\nday.\r\nResults: Cysteamine concentrations were satisfactorily described by a one-compartment model. Parameter\r\nestimates were standardized for a mean standard bodyweight using an allometric model. WBC cystine levels were\r\nadequately described by an indirect response model where the first-order removal rate constant is stimulated by\r\nthe cysteamine concentrations.\r\nConclusions: According to simulations, in order to increase the percentage of patient with cystine levels below 1\r\nnmol half-cystine/mg of protein, the current dosages could be changed as follows: 80 mg/kg/day (QID) from 10 to\r\n17 kg, 70 mg/kg/day (QID) from 17 to 25 kg, 60 mg/kg/day (QID) from 25 to 40 kg and 50 mg/kg/day (QID) from\r\n40 to 70 kg (these dosages remain under the maximum recommended dose). However an 8-hourly daily treatment\r\n(TID) did not provide acceptable cystine levels and should not be proposed
Loading....