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4CPS-253 The importance of the pharmacokinetic profile in patients with ultra-rare diseases: a case report
  1. C Castillo-Martin,
  2. J Cordero-Ramos,
  3. R Castillejo García,
  4. A Martínez Suárez,
  5. L Rendón De Lope,
  6. M Camean Fernández
  1. Hospital Universitario Virgen Macarena, Pharmacy, Seville, Spain


Background and importance Mucopolysaccharidosis VII (MPSVII), also known as Sly syndrome, is an ultra-rare disease characterised by deficiency of β-glucuronidase. Sly phenotypes vary from severe forms with hydrops fetalis and skeletal dysplasia, hepatosplenomegaly, heart valve abnormalities and mental retardation, to milder forms with fewer manifestations.

Aim and objectives To compare the vancomycin pharmacokinetic (PK) profile observed in a newborn with MPSVII with that expected in an average neonate.

Material and methods Clinical data were collected from the electronical medical record (Diraya), and an extensive literature research was made using different electronic databases (Pubmed, Scopus). Serum concentration–time profiles were adjusted to a one compartment neonatal population PK model incorporating body weight and renal function as the significant covariates, using the Abottbase PK System (PKS) programme.

Results The patient was a 26-day-old male, with a postmenstrual age of 38 weeks, and diagnosed with MPS VII, who initially had phlebitis and fever during his stay in the neonatal intensive care unit. His blood cultures were positive for coagulase negative Staphylococcus aureus. The patient was treated with vancomycin 10 mg/kg/8 hours intravenously. PK were evaluated before the sixth dose, with weight of 2.2 kg, height 44 cm and a creatinine serum level of 0.92 mg/L. After obtaining a serum level of 123.6 µg/mL (normal trough range 10–15 µg/mL), vancomycin was stopped. After 2 days, serum levels were 11.4 µg/mL, so vancomycin was restarted at 10 mg/kg/12 hours. After four administrations, serum levels were again out of range (48.2 µg/mL), and the antimicrobial was switched to cloxacillin. Based on the vancomycin levels, we estimated a half-life of 15.8 hours, instead of the 4–8 hours described. The distribution volume calculated was 1.99 L with a clearance of 0.088 L/hour. The expected distribution volume was 1.8 L and a clearance of 0.148 L/hour.

Unfortunately, the baby passed away 3 days later due to other complications.

Conclusion and relevance A 2–3 times greater half-life was observed in this patient with Sly syndrome. The large accumulation of vancomycin was not described in the literature and was not expected with the features of this disease, highlighting the importance of therapeutic drug monitoring in patients with ultra-rare diseases whose pharmacokinetics could be disturbed by factors still unknown.

Conflict of interest No conflict of interest

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