Population Pharmacokinetics of Doxycycline in Children.
2019 Sep 23
Journal Article
Authors:
Thompson, E.J.;
Wu, H.;
Melloni, C.;
Balevic, S.;
Sullivan, J.E.;
Laughon, M.;
Clark, K.M.;
Kalra, R.;
Mendley, S.;
Payne, E.H.;
Erinjeri, J.;
Gelber, C.E.;
Harper, B.;
Cohen-Wolkowiez, M.;
Hornik, C.P.
Secondary:
Antimicrob Agents Chemother
PMID:
31548185
Abstract:
Doxycycline is a tetracycline-class antimicrobial labeled by the United States (U.S.) Food and Drug Administration for children >8 years of age for many common childhood infections. Doxycycline is not labeled for children ≤8 years of age, due to the association between tetracycline class antibiotics and tooth staining, although doxycycline may be used off-label in severe conditions. Accordingly, there is a paucity of pharmacokinetic (PK) data to guide dosing in children 8 years and younger. We leveraged opportunistically-collected plasma samples after intravenous (IV) and oral doxycycline doses received per standard of care to characterize the PK of doxycycline in children of different ages, and evaluated the effect of obesity and fasting status on PK parameters.We developed a population PK model of doxycycline using data collected from 47 patients 0-18 years of age, including 14 participants ≤8 years. We developed a 1 compartment PK model and found doxycycline clearance to be 3.32 L/h/70 kg and volume to be 96.8 L/70kg for all patients; comparable to values reported in adults. We estimated a bioavailability of 89.6%, also consistent with adult data. Allometrically scaled clearance and volume of distribution did not differ between children 2 to ≤8 years of age and children >8 to ≤18 years of age, suggesting that younger children may be given the same per kg dosing. Obese and fasting status were not selected for inclusion in the final model. Additional doxycycline PK samples collected in future studies may be used to improve model performance and maximize its clinical value.
