NextDose: A web-based Bayesian dose forecasting tool

Last updated 27 July 2021



Target Concentration

Caffeine is used to reduce apneic events in premature neonates. The current standard treatment is based on an acceptable range of concentrations between 10 and 20 mg/L which is the same range recommended for theophylline for the treatment of severe asthma. No concentration controlled study has been performed in neonates to confirm this range.

A prospective study of the pharmacokinetics of caffeine in premature neonates (Yang, Holford et al. 2019) also collected data on the time to event of apneic events (Holford, Yang et al. 2019). The caffeine concentration reducing the hazard of an apneic event by 50% was 1.8 mg/L with a predicted maximum reduction of 49%. This predicts that a target concentration of 5 mg/L would reduce the hazard by nearly 50%.

The NextDose pharmacokinetic model is based on (Yang, Holford et al. 2019).

Copyright All rights reserved | Developed by Sam Holford & Nick Holford 2012-2021


Holford, N., X. Yang, Z. Jiang, H. Shen, J. Shi, X. Shu, Y. Huang, J. Zhao, J. Tang and D. Mu (2019). "Rational dosing of caffeine using target concentration intervention to improve treatment of apnea of prematurity Abstr 9027 []." PAGE 28.

Yang, Y., N. Holford, Z. Jiang, H. Shen, J. Shi, X. Shu, Y. Huang, J. Zhao, J. Tang and D. Mu (2019). A Population Pharmacokinetic Study of Caffeine Citrate in Chinese Premature Neonates. PAGANZ. Auckland.