BackgroundCysteamine has recently been shown to have in vitro properties potentially therapeutically beneficial in cystic fibrosis (CF). In this study we investigated the antimicrobial and mucolytic activity of cysteamine against the complex biologic matrix of CF sputum.MethodsSputum samples were obtained from 23 CF adults. Sputum polymicrobial content after in vitro exposure to cysteamine and standard CF antibiotics was assessed after a single exposure and after 14 days low-dose exposure. The effect of cysteamine on sputum spinnbarkeit was assessed.FindingsCysteamine reduced sputum polymicrobial burden by 3 · 18 (95% CI 2 · 30–4 · 07, p < 0.001) log10 units after 24 h incubation. Combined cysteamine and tobramycin reduced polymicrobial burden by a further 3 · 75 (95% CI 2 · 63–5 · 07, p < 0 · 001) log10 units above that seen with tobramycin. Repeated low dosing with cysteamine reduced sputum polymicrobial load from day 10 onwards (p = 0.032). Cysteamine reduced CF sputum viscoelasticity, sputum spinnbarkeit cysteamine 11.1 mm/s (95% CI 3.95–18.2) vs DNAse 1.69 mm/s (95% CI 0.73–2.65), p = 0.016. Cysteamine was active against Mycobacterium abscessus as a monotherapy and also potentiated the effects of amikacin and azithromycin.ConclusionFurther investigation is required into the therapeutic potential of cysteamine in CF to treat emerging as well as established microbial pathogens and as a mucolytic agent.

Background and ObjectiveCysteamine is licensed for use in nephropathic cystinosis but preclinical data suggest a role in managing cystic fibrosis (CF). This study aimed to determine whether oral cysteamine is absorbed in adult CF patients and enters the bronchial secretions. Tolerability outcomes were also explored.MethodsPatients ≥18 years of age, weighing >50 kg with stable CF lung disease were commenced on oral cysteamine bitartrate (Cystagon®) 450 mg once daily, increased weekly to 450 mg four times daily. Serial plasma cysteamine concentrations were measured for 24 h after the first dose. Participants were reviewed every week for 6 weeks, except at 4 weeks. Plasma cysteamine concentrations were measured 8 h after dosing when reviewed at 1, 2 and 3 weeks and 6 h after dosing when reviewed at 5 weeks. Sputum cysteamine concentration was also quantified at the 5-week assessment.ResultsSeven of the ten participants reported adverse reactions typical of cysteamine, two participants discontinued intervention. Following the first 450-mg dose, mean (SD) maximum concentration (Cmax) was 2.86 (1.96) mg/l, the time corresponding to Cmax (Tmax) was 1.2 (0.7) h, the half-life (t½) was 3.7 (1.7) h, clearance (CL/F) 89.9 (30.5) L/h and volume of distribution (Vd/F) 427 (129) L. Cysteamine appeared to accumulate in sputum with a median (interquartile range) sputum:plasma cysteamine concentration ratio of 4.2 (0.98–8.84).ConclusionOral cysteamine is absorbed and enters the bronchial secretions in patients with CF. Although adverse reactions were common, the majority of patients continued with cysteamine. Further trials are required to establish the risk benefit ratio of cysteamine therapy in CF.

Plasma phenytoin levels were measured in 60 patients under steady-state conditions for a period of six weeks. During the trial, the preparation of phenytoin was changed from Phenytoin BP (Regent) to Epanutin Infatabs. A significant increase in plasma phenytoin levels following the change of tablet was matched by a decrease in the number of seizures.