Computing optimal drug dosing with OptiDose: implementation in NONMEM

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

<p xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="first" dir="auto" id="d2171419e146">Determining a drug dosing recommendation with a PKPD model can be a laborious and complex task. Recently, an optimal dosing algorithm (OptiDose) was developed to compute the optimal doses for any pharmacometrics/PKPD model for a given dosing scenario. In the present work, we reformulate the underlying optimal control problem and elaborate how to solve it with standard commands in the software NONMEM. To demonstrate the potential of the OptiDose implementation in NONMEM, four relevant but substantially different optimal dosing tasks are solved. In addition, the impact of different dosing scenarios as well as the choice of the therapeutic goal on the computed optimal doses are discussed. </p>

Related collections

Most cited references 23

Record: found
Abstract: found
Article: not found

Optimal control of the chemotherapy of HIV.

S Serbin, Suzanne Lenhart, Ralf Kirschner (1997)

Using an existing ordinary differential equation model which describes the interaction of the immune system with the human immunodeficiency virus (HIV), we introduce chemotherapy in an early treatment setting through a dynamic treatment and then solve for an optimal chemotherapy strategy. The control represents the percentage of effect the chemotherapy has on the viral production. Using an objective function based on a combination of maximizing benefits based on T cell counts and minimizing the systemic cost of chemotherapy (based on high drug dose/strength), we solve for the optimal control in the optimality system composed of four ordinary differential equations and four adjoint ordinary differential equations.

0 comments Cited 82 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: not found
Article: not found

Optimal control of an HIV immunology model

Hem Joshi (2002)

0 comments Cited 62 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Comparison of four basic models of indirect pharmacodynamic responses.

Natalie Dayneka, Varun Garg, William Jusko (1993)

Four basic models for characterizing indirect pharmacodynamic responses after drug administration have been developed and compared. The models are based on drug effects (inhibition or stimulation) on the factors controlling either the input or the dissipation of drug response. Pharmacokinetic parameters of methylprednisolone were used to generate plasma concentration and response-time profiles using computer simulations. It was found that the responses produced showed a slow onset and a slow return to baseline. The time of maximal response was dependent on the model and dose. In each case, hysteresis plots showed that drug concentrations preceded the response. When the responses were fitted with pharmacodynamic models based on distribution to a hypothetical effect compartment, the resulting parameters were dose-dependent and inferred biological implausibility. Indirect response models must be treated as distinct from conventional pharmacodynamic models which assume direct action of drugs. The assumptions, equations, and data patterns for the four basic indirect response models provide a starting point for evaluation of pharmacologic effects where the site of action precedes or follows the measured response variable.