Pharmacokinetics of colistin after nebulization or intravenous administration of colistin methanesulphonate (Colimycin®) to cystic fibrosis patients.
J Cyst Fibros
; 19(3): 421-426, 2020 05.
Article
in En
| MEDLINE
| ID: mdl-31501050
ABSTRACT
OBJECTIVES:
Colistin, administered as the prodrug colistin methanesulphonate (CMS), is an antibiotic frequently administered as aerosol in cystic fibrosis (CF) patient. Our aim was to assess the plasma PK of colistin in CF patients treated with CMS administered intravenously or as aerosol and to compare these results with those previously reported in healthy volunteers.METHODS:
Six CF patients were included, CMS and colistin concentrations were measured in plasma, urine and sputum. Either after single intravenous administration of 2 Million International Unit (MIU) or after repeated nebulizations of 2 MIU of CMS. PK of CMS and colistin were assessed by a mixed effect modeling approach.RESULTS:
Renal clearance of CMS was lower in CF patients compared to that previously reported in healthy volunteers (64.3â¯mL/min (RSEâ¯=â¯15%) vs. 103â¯mL/min (RSEâ¯=â¯8%)). However, apparent clearance of colistin was higher in CF patients compared to healthy volunteers (124â¯mL/min (RSEâ¯=â¯13%) vs. 48.7â¯mL/min (RSEâ¯=â¯15%)), resulting in reduced systemic exposure to colistin (dose normalized AUC (2 MIU) of 7.4â¯h.mg/L/MIU vs. 11.2â¯h.mg/L/MIU). After repeated nebulizations, colistin concentrations were very low in plasma (<0.21â¯mg/L).CONCLUSIONS:
Although our study suggests a lower median dose normalized colistin plasma concentrations in CF patients compared with healthy controls, this difference was not significant and a larger study is needed to substantiate this.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Administration, Inhalation
/
Colistin
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Cystic Fibrosis
/
Administration, Intravenous
Limits:
Adult
/
Female
/
Humans
/
Male
Language:
En
Journal:
J Cyst Fibros
Year:
2020
Document type:
Article
Affiliation country:
France