Pharmacokinetics of zanamivir in critically ill patients undergoing continuous venovenous hemofiltration.

BACKGROUND: Limited data exist for dosing of zanamivir in the setting of CVVH in the intensive care unit (ICU). Our objective is to report the pharmacokinetics and sieving coefficient (Sv) of zanamivir in patients receiving continuous venovenous hemofiltration (CVVH). METHODS: In this prospective observational study, patients of ≥18 years admitted to the ICU with a life-threatening Influenza A or B infection, treated with zanamivir i.v. undergoing CVVH were included. Patients received a zanamivir loading dose of 600 mg i.v., 12 h later followed by maintenance dosages two times daily according to the treating physician. Per patient, nine CFT plasma and nine ultrafiltrate samples were drawn on day 2 of treatment and analysed with a validated HPLC-MS/MS method. RESULTS: Four patients were included in the study. The zanamivir elimination half-life was prolonged with 5.6-9.9 h, compared to patients with normal renal function. A Sv of approximately 1.0 was identified, with unrestricted transport of zanamivir to the ultrafiltrate. CONCLUSIONS: Zanamivir is well cleared by CVVH. In absence of the possibility for therapeutic drug monitoring, the ultrafiltration rate seems as a good surrogate parameter to estimate the CLCVVH and may help guide the dosing of zanamivir.

Assessing methods of measuring medication adherence in chronically ill children-a narrative review.

Nonadherence in children who use long-term medication is a serious problem and assessing adherence is an important step to provide solutions to this problem. Medication adherence can be measured by several methods, including (a) self-report questionnaires or structured interviews, (b) therapeutic drug monitoring (TDM), (c) electronic devices, and (d) pick-up/refill rates. The objective of this narrative review is to provide an overview of the literature about methods for the measurement of medication adherence in chronically ill children and adolescents. Therefore, we conducted a literature search by using multiple databases. Four methods of monitoring medication adherence are presented for the most described chronic diseases: asthma, HIV/AIDS, epilepsy, diabetes mellitus and ADHD. First, 10 commonly used self-report questionnaires and structured interviews are described, including the main characteristics, (dis)advantages and their validation studies. Second, the use of TDM in pediatric trials for medication adherence measurement is discussed. New sampling methods (e.g. dried blood spot) and sampling matrices (e.g. hair, saliva and urine) have shown their benefits for TDM in children. Third, electronic devices to measure medication adherence in children are presented, being developed for several drug administration routes. Fourth, the analyses, advantages and disadvantages of pharmacy data are discussed. The usage of this data requires specific calculations and interpretations to assess adherence. As presented in this review, every adherence method has specific (dis)advantages. When deciding which adherence method is applicable, validity and generalizability should be taken into account. Combining multiple methods seems to offer the best solution in the daily clinical practice.