Steady‐state pharmacokinetics and pharmacodynamics of cysteamine bitartrate in paediatric nephropathic cystinosis patients
EB Belldina, MY Huang, JA Schneider… - British journal of …, 2003 - Wiley Online Library
EB Belldina, MY Huang, JA Schneider, RC Brundage, TS Tracy
British journal of clinical pharmacology, 2003•Wiley Online LibraryAims Cysteamine is used to reduce tissue cystine content in patients suffering from
nephropathic cystinosis. The objectives of the current study were to investigate
pharmacokinetics and pharmacodynamics of cysteamine bitartrate in children and young
adults with nephropathic cystinosis. Methods Cysteamine bitartrate was administered to 11
cystinosis patients at their regular dose level in a single‐dose, open‐label, steady‐state
study. Blood samples were collected and analysed for plasma cysteamine and white blood …
nephropathic cystinosis. The objectives of the current study were to investigate
pharmacokinetics and pharmacodynamics of cysteamine bitartrate in children and young
adults with nephropathic cystinosis. Methods Cysteamine bitartrate was administered to 11
cystinosis patients at their regular dose level in a single‐dose, open‐label, steady‐state
study. Blood samples were collected and analysed for plasma cysteamine and white blood …
Aims Cysteamine is used to reduce tissue cystine content in patients suffering from nephropathic cystinosis. The objectives of the current study were to investigate pharmacokinetics and pharmacodynamics of cysteamine bitartrate in children and young adults with nephropathic cystinosis.
Methods Cysteamine bitartrate was administered to 11 cystinosis patients at their regular dose level in a single‐dose, open‐label, steady‐state study. Blood samples were collected and analysed for plasma cysteamine and white blood cell cystine content and pharmacokinetic and pharmacodynamic parameters estimated by NONMEM analysis using a linked pharmacokinetic–pharmacodynamic model.
Results Cysteamine was rapidly cleared from the plasma (mean CL/F = 32.3 ml min−1 kg−1, range = 17.3–52.2), appeared to be extensively distributed (mean Vss/F = 15.1 l, range 2.7–32.3) and exhibited a mean Tmax of 1.4 h. White blood cell cystine content post‐dosing was significantly decreased compared with pre‐ and post‐dose values (average decrement approximately 47%). A counter‐clockwise hysteresis was noted in all patients, suggestive of a lag time (mean Tlag = 0.44 h, range 0.22–0.92) between drug concentration and effect.
Conclusions The results of this study establish that cysteamine is rapidly cleared from the plasma but that an every 6 h dosing interval adequately maintains white blood cell cystine content below the target of 1 nmol cystine per mg protein.
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