Het Nederlands Platform voor Farmaceutisch Onderzoek (NPFO) presenteert onderzoek in de farmaceutische wetenschappen. De nadruk ligt op klinische toepassing zoals medicatieveiligheid, patiëntenzorg, formulering, analyse, farmacologie en casuïstiek.
Pharmacokinetics and tolerability of once daily double dose tobramycin inhalation in cystic fibrosis using controlled and conventional nebulization: comparison between PARI-LC Plus and AKITA nebulizer
OBJECTIVE
Better treatment outcomes in cystic fibrosis (CF) may be expected by changing standard twice daily tobramycin inhalation with the conventional PARI-LC Plus nebulizer to once daily inhalation of the double dose with the controlled-inhalation AKITA nebulizer. We aimed to determine pharmacokinetics (PK) and safety of once daily inhalation of the double recommended tobramycin dose with the AKITA in patients with CF. Systemic absorption can be used as surrogate for safety.
DESIGN and METHODS
In a randomized open-label crossover pilot study, PK of inhaled tobramycin in 10 adult CF patients was assessed following inhalation of the double recommended dose with the AKITA (300 mg fill dose) and PARI-LC Plus (600 mg fill dose). Blood samples were drawn until 24 hours after inhalation.
RESULTS
No significant differences were found in the maximum and trough serum levels, time to maximum level and area under the curve (0-24 hours). Both maximum and trough levels were well below their toxic limits for both nebulizers and for all patients. Both inhalations were well tolerated and no serious adverse events occurred. Nebulization time was 33% shorter with AKITA.
CONCLUSION
Once daily inhalation of the double tobramycin dose with the controlled-inhalation AKITA nebulizer resulted in safe serum levels, with comparable systemic exposure to once daily PARI-LC Plus inhalation and higher peak levels compared to the standard twice daily dosing regimen. Inhalation with both nebulizers was well tolerated. Nebulization time was significantly shortened, less side effects were reported and a higher degree of satisfaction was attained with the AKITA nebulizer.
Evaluation of a new Dutch guideline for vancomycin dosing and population pharmacokinetics of vancomycin for preterm and term neonates
OBJECTIVE
In May 2015 the Dutch pediatric formulary (Kinderformularium) introduced a new guideline for dosing of vancomycin in neonates. The primary aim of this study was to validate this guideline by assessing the percentage of therapeutic initial trough serum concentrations in a cohort of (pre)term neonates. The secondary aim of this study was to describe the population pharmacokinetics (PPK) of vancomycin in (pre)term neonates.
METHODS
In this prospective study, (pre)term neonates were included when admitted to the Neonatology department of the Academic Medical Center, Amsterdam from May 2015 to June 2017. Vancomycin dosing was performed according to the new guideline. Serum concentrations were measured prior to the administration of the fifth dose. Trough levels in the range of 10 to 15 mg/L were considered therapeutic. PPK parameters were estimated by nonlinear mixed-effects modeling.
RESULTS
Forty patients were included for the primary aim and 42 patients for the secondary aim of this study. The main category of patients were premature neonates with a postnatal age of 1 to 4 weeks (n = 27, 68%). In this group 15 patients (56%) had a subtherapeutic vancomycin serum level, while therapeutic and supratherapeutic levels were found in 7 (26%) and 5 (19%) of the patients, respectively. The PPK were best described by an allometric, one-compartment model. Inter-patient variability in clearance could be explained by variation in renal function and postmenstrual age.
CONCLUSION
The new dosing guideline does not produce therapeutic vancomycin concentrations in the majority of premature neonates from 1 to 4 weeks old. Further research is needed to optimize dosing of vancomycin in neonates.