Pharmacodynamics rebound

Sharma, A., Ebling, W., and Jusko, W., Precursor-dependent indirect pharmacodynamic response model for tolerance and rebound phenomena, Journal of Pharmaceutical Sciences, Vol. 87, No. 12, 1998, pp. 1577-1584. 

An extension of indirect response models are precursor pool-dependent indirect response models that include the lihera-tion of an endogenous compound from a storage pool. These models possess the unique ability to characterize hoth tolerance and rebound phenomena [90]. Such a model was, for example, used to describe the effect of interferon- Sla on neopterin, an endogenous marker for cell-mediated immunity, in humans and monkeys (Fig. 8) [91, 92]. The primary elimination mechanism of interferon- 8 la was modeled as receptor-mediated endo-cytosis, and the pharmacodynamic model was driven by the amount of internalized drug-receptor complex DR ... 

Slow receptor dissociation brings the potential for extended pharmacodynamics beyond that suggested by pharmacokinetic predictions. In monotherapy trials of CCR5 antagonists the rebound in viral load after treatment discontinuation does not appear to be immediate, but is delayed by 1-2 days for vicriviroc [145] and aplaviroc [146] and up to 5 days for maraviroc [147]. It seems likely that a combination of pharmacokinetic half-life and slow receptor offrate is required for optimal efficacy [148]. 

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