TY - JOUR
T1 - Saliva monitoring of prednisolone in children with first onset steroid-sensitive nephrotic syndrome
T2 - Is it possible?
AU - Veltkamp, Floor
AU - Pistorius, Marcel C. M.
AU - Mak-Nienhuis, Elske M.
AU - Schreuder, Michiel F.
AU - Bouts, Antonia H. M.
AU - Mathôt, Ron A. A.
N1 - Publisher Copyright: © 2024 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.
PY - 2024
Y1 - 2024
N2 - Aims: Prednisolone is the cornerstone of treatment for idiopathic nephrotic syndrome in children, but is associated with marked side-effects. Therapeutic drug monitoring using saliva would be a patient-friendly option to monitor prednisolone treatment. To assess the feasibility of saliva monitoring, we described the pharmacokinetics (PK) of unbound prednisolone in plasma and saliva of children with first onset steroid-sensitive nephrotic syndrome (SSNS). Methods: Children (age 2–16 years) with SSNS participating in a randomized, placebo-controlled trial with levamisole were treated with an 18-week tapering schedule of prednisolone. Five serial samples were collected at 4 (saliva) and 8 weeks (saliva and plasma) after first onset. A nonlinear mixed-effects model was used to estimate the PK parameters of unbound prednisolone and the saliva-to-plasma ratio. Monte Carlo simulations were performed to assess the predictive performance of saliva monitoring. Results: From 39 children, 109 plasma and 275 saliva samples were available. Estimates (relative squared error) of unbound plasma clearance and volume of distribution were 93 (5%) L h−1 70 kg−1 and 158 (7%) L 70 kg−1, respectively. Typical saliva-to-plasma ratio was 1.30 (8%). Monte Carlo simulations demonstrated that on basis of 4 saliva samples and a single plasma sample unbound plasma area-under-the-concentration–time curve can be predicted within 20% imprecision in 79% of the patients compared to 87% based on 4 plasma samples. Conclusion: Saliva proved to be a reliable and patient-friendly option to determine prednisolone plasma exposure in children with SSNS. This opens opportunities for further PK and pharmacodynamics studies of prednisolone in a variety of paediatric conditions.
AB - Aims: Prednisolone is the cornerstone of treatment for idiopathic nephrotic syndrome in children, but is associated with marked side-effects. Therapeutic drug monitoring using saliva would be a patient-friendly option to monitor prednisolone treatment. To assess the feasibility of saliva monitoring, we described the pharmacokinetics (PK) of unbound prednisolone in plasma and saliva of children with first onset steroid-sensitive nephrotic syndrome (SSNS). Methods: Children (age 2–16 years) with SSNS participating in a randomized, placebo-controlled trial with levamisole were treated with an 18-week tapering schedule of prednisolone. Five serial samples were collected at 4 (saliva) and 8 weeks (saliva and plasma) after first onset. A nonlinear mixed-effects model was used to estimate the PK parameters of unbound prednisolone and the saliva-to-plasma ratio. Monte Carlo simulations were performed to assess the predictive performance of saliva monitoring. Results: From 39 children, 109 plasma and 275 saliva samples were available. Estimates (relative squared error) of unbound plasma clearance and volume of distribution were 93 (5%) L h−1 70 kg−1 and 158 (7%) L 70 kg−1, respectively. Typical saliva-to-plasma ratio was 1.30 (8%). Monte Carlo simulations demonstrated that on basis of 4 saliva samples and a single plasma sample unbound plasma area-under-the-concentration–time curve can be predicted within 20% imprecision in 79% of the patients compared to 87% based on 4 plasma samples. Conclusion: Saliva proved to be a reliable and patient-friendly option to determine prednisolone plasma exposure in children with SSNS. This opens opportunities for further PK and pharmacodynamics studies of prednisolone in a variety of paediatric conditions.
KW - clinical pharmacology
KW - paediatric nephrology
KW - pharmacokinetics
UR - http://www.scopus.com/inward/record.url?scp=85190457131&partnerID=8YFLogxK
U2 - 10.1111/bcp.16066
DO - 10.1111/bcp.16066
M3 - Article
C2 - 38599658
SN - 0306-5251
JO - British journal of clinical pharmacology
JF - British journal of clinical pharmacology
ER -