Dose increase needed in most cystic fibrosis lung transplantation patients when changing from twice- to once-daily tacrolimus oral administration

• Published in: European journal of clinical pharmacology 2015-06, Vol.71 (6), p.715-722
• Main Authors: Soto, Gustavo Adolfo Centeno, Ruiz-Antorán, Belén, Laporta, Rosalía, Sancho, Arantxa, Lázaro, María Teresa, Herrera, Concepción Payares, Salcedo, Isabel, Cos, Maria Angeles, Torres, Ferrán, Usetti, Piedad, Avendaño-Sola, Cristina
• Format: Article
• Language: English
• Subjects: Administration, Oral; Adult; Area Under Curve; Biomedical and Life Sciences; Biomedicine; Cystic fibrosis; Cystic Fibrosis - metabolism; Cystic Fibrosis - physiopathology; Drug Administration Schedule; Drug therapy; Female; Humans; Immunosuppressive Agents - administration & dosage; Immunosuppressive Agents - pharmacokinetics; Lung Transplantation - methods; Lungs; Male; Pharmacokinetics and Disposition; Pharmacology; Pharmacology/Toxicology; Tacrolimus - administration & dosage; Tacrolimus - pharmacokinetics; Transplants & implants; Young Adult
• ISSN: 0031-6970; 1432-1041
• DOI: 10.1007/s00228-015-1859-2

Aim The aim of this pharmacokinetic (PK) study was to evaluate tacrolimus (TAC) exposure in stable cystic fibrosis (CF) lung transplant (LT) recipients, converted from TAC twice daily to TAC once daily in an open-label, prospective, single-centre study. Methods Eligible patients were post-transplant CF patients (18–65 years) with stable lung function, on stable doses of TAC twice daily and who were candidates to switch to TAC once daily. Twelve consecutive patients were included in the study. Patients had their first PK analysis on day 1, still under the stable TAC twice-daily regimen, and were converted to TAC once daily from day 2 onwards. The doses were adjusted according to clinical judgement to achieve target levels, and a second 24-h PK period profile was obtained once the patient was on a stable dosage on the therapeutic range. Results The mean total (SD) daily dose of TAC twice daily at baseline upon enrolment was 0.17 (0.10) mg/kg/day. The mean (SD) daily dose of TAC once daily after adjustments was 0.22 (0.12) mg/kg/day. In order to achieve target C min levels with a similar AUC 0–24 , 82 % of subjects who were converted to TAC once daily required an increase of dose, in a range of 0–66.7 %, with a mean dose increase of 28 %. Conclusions Our study results indicate that the switch for conversion from TAC twice daily to TAC once daily in patients with CF may need dose adjustment in order to reach levels within the therapeutic target.