Ranjan Dohil1, Betty L Cabrera1, Jon Gangoiti1, Patrice Rioux1. 1. Department of Pediatrics, University of California, San Diego, CA, USARady Children's Hospital, San Diego, CA, USARaptor Pharmaceuticals, Novato, CA, USA.
Abstract
OBJECTIVES: Treatment with cysteamine reduces the rate of progression to end-stage kidney disease in cystinosis. Although food is often taken with cysteamine to reduce associated gastrointestinal symptoms, this may alter the bioavailability of cysteamine. METHODS: This is a prospective, randomized, 3-treatment study to determine the effects of fasting and high-fat/calorie and high-protein meals on cysteamine absorption in healthy adult controls. On 3 separate days, serial plasma cysteamine levels were measured after cysteamine bitartrate 500 mg was ingested while fasting and also 30 minutes after high-fat/calorie and high-protein diets. Gastrointestinal (GI) symptoms were also monitored. RESULTS:Eight participants (5 men) were enrolled. Cysteamine absorption, as measured by area under the cysteamine concentration-time curve (AUC0-∞ ) while fasted and following high-fat/calorie and high-protein meals, was 3618 ± 372 min·μM, 2799 ± 405 min·μM (P = .04 vs fasted), and 2457 ± 353min·μM (P = .005), respectively, and the mean Cmax values for participants were 26.3 ± 3.5 μM, 22.4 ± 5.6 μM (P = .16 vs fasted), and 17.2 ± 2.6 μM (P = .036 vs fasted), respectively. Mild GI symptoms were reported in 3 participants. CONCLUSIONS:Cysteamine absorption may be decreased by 30% when taken with food as compared with the fasting state. Food causes wide variation in tmax and Cmax for cysteamine. 2012 American College of Clinical Pharmacology.
RCT Entities:
OBJECTIVES: Treatment with cysteamine reduces the rate of progression to end-stage kidney disease in cystinosis. Although food is often taken with cysteamine to reduce associated gastrointestinal symptoms, this may alter the bioavailability of cysteamine. METHODS: This is a prospective, randomized, 3-treatment study to determine the effects of fasting and high-fat/calorie and high-protein meals on cysteamine absorption in healthy adult controls. On 3 separate days, serial plasma cysteamine levels were measured after cysteamine bitartrate 500 mg was ingested while fasting and also 30 minutes after high-fat/calorie and high-protein diets. Gastrointestinal (GI) symptoms were also monitored. RESULTS: Eight participants (5 men) were enrolled. Cysteamine absorption, as measured by area under the cysteamine concentration-time curve (AUC0-∞ ) while fasted and following high-fat/calorie and high-protein meals, was 3618 ± 372 min·μM, 2799 ± 405 min·μM (P = .04 vs fasted), and 2457 ± 353 min·μM (P = .005), respectively, and the mean Cmax values for participants were 26.3 ± 3.5 μM, 22.4 ± 5.6 μM (P = .16 vs fasted), and 17.2 ± 2.6 μM (P = .036 vs fasted), respectively. Mild GI symptoms were reported in 3 participants. CONCLUSIONS:Cysteamine absorption may be decreased by 30% when taken with food as compared with the fasting state. Food causes wide variation in tmax and Cmax for cysteamine. 2012 American College of Clinical Pharmacology.
Authors: Graham Devereux; Sandra Steele; Kairen Griffiths; Edward Devlin; Douglas Fraser-Pitt; Seonaidh Cotton; John Norrie; Henry Chrystyn; Deborah O'Neil Journal: Clin Drug Investig Date: 2016-08 Impact factor: 2.859
Authors: Nadine Pavloff; Terry A Hauser; Chris Williams; Sara Louis Isbell; Ben Cadieux; Mark Johnson Journal: Drug Des Devel Ther Date: 2018-09-06 Impact factor: 4.162