Computational Opioid Prescribing: A Novel Application of Clinical Pharmacokinetics

Abstract

We implemented a pharmacokinetics-based mathematical modeling technique using algebra to assist pre-scribers with point-of-care opioid dosing. We call this technique computational opioid prescribing (COP). Because population pharmacokinetic parameter values are needed to estimate drug dosing regimen designs for individual patients using COP, and those values are not readily available to prescribers because they exist scattered in the vast pharmacology literature, we estimated the population pharmacokinetic parameter values for 12 commonly prescribed opioids from various sources using the bootstrap resampling technique. Our results show that opioid dosing regimen design, evaluation, and modification is feasible using COP. We conclude that COP is a new technique for the quantitative assessment of opioid dosing regimen design evaluation and adjustment, which may help prescribers to manage acute and chronic pain at the point-of-care. Potential benefits include opioid dose optimization and minimization of adverse opioid drug events, leading to potential improvement in patient treatment outcomes and safety.

A New Model for Using Quantitative Urine Testing as a Diagnostic Tool for Oxycodone Treatment and Compliance

“…A clinician could take the following steps: (1) Determine initial dosing regimen using the COP model. 8 (2) Use our model to calculate the expected OCNP based upon the dose regimen. (3) Once the patient has taken OC for at least 5 half-lives, test OCNP (OC half-life = 4.5 hours).…”

“…But to predict OCNP, we needed to measure k u , the rate at which the body eliminates OC into urine from the bloodstream. Figure 1, Model A, 8 shows a simplified diagram of OC's path through a patient's body. The patient takes a pill (D po ), which enters the gastrointestinal (GI) tract (D GI ) and is absorbed into the bloodstream (D B ).…”

“…We treated each patient with OC, according to a dosing regimen determined by computational opioid prescribing (COP). 8 …”

“…This value is reasonably close to our previous estimate of 0.174 ± 0.034 h −1 (95% confidence interval [CI]: 0.167, 0.180), which we computed using data from other studies in the literature of OC pharmacokinetics. 8 In addition, we used our model and the Smith et al 23 data to estimate OC's elimination rate into the urine k u . We found that k u = 0.0282 ± 0.0058 h −1 [21 ± 5%].…”

A Transit Compartment Model Unmasks OxyContin's Reflective Pharmacokinetics From Urine Measurements in Humans

“…OXC's absorption pattern makes it difficult to quantify its pharmacokinetics, which, although studied extensively, 2,[8][9][10][11][12][13][14][15][16] have been characterized only to a limited extent. One reason is that OXC's absorption cannot be directly measured.…”