ReferencesAcknowledgements

Methods

Background

Conclusions

Results

We chose which drugs to analyze for nonlinear pharmacokinetics by searching for new drug approvals on the FDA website from the years 2000-2015. We recorded the

generic names, brand names, mechanism of action, metabolic pathway, bioavailability and indications of all drugs approved in this time period. The information on the

package insert was used to determine which drugs exhibited nonlinear kinetics and the mechanism of nonlinear kinetics. When this information wasn’t available from the

package insert, we used Pubmed to find additional information.

Key Words● Nonlinear, non-proportional, non-proportional, saturable, Michaelis-Menten

kinetics

Statistical Analysis● Student t-test: examines the comparison between the amount of linear vs.

nonlinear drugs approved from 2000-2015● Fisher’s exact test: comparison of drug classes between linear and nonlinear

drugs approved from 2000-2015

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1. College of Pharmacy, University of Iowa, Iowa City, IA 52242, USA2. The Division of Pharmaceutics and Translational Therapeutics, College of Pharmacy, University of Iowa, Iowa City, IA 52242, USA

Giang Ho1, Erik Gunderson1, Adaeze Emecheta1, Sarah Blackwell1, Guohua An2

Nonlinear pharmacokinetics (PK) can cause increases in drug concentrations that are disproportionately high or low relative to the change in dose. The cause of nonlinear PK can be from absorption, metabolism, distribution, dissolution, or target-mediated drug disposition (TMDD). Nonlinear pharmacokinetic drugs pose a challenge in therapy management due to their complex nature and presently there are no updated databases dedicated to this group despite their growing number on the market. Our objective was to use the FDA database to search for new drugs with nonlinear PK properties and analyze trends within this group. Any correlational relationship and current clinical utilities of nonlinear PK drugs were analyzed, which served as a basis for developing a clinical guideline to improve the therapeutic drug management and patient care.

We greatly appreciate Sharon Huang and James Nguyen for helping us collecting the data from 2005-2010, and Ronilda D’cunha for helping us analyze the data.

Clinical guideline(s) examined

Nonlinear drugs listed for TDM

Type of nonlinear drugs

Gao et al[9] Erlotinib, Gefitinib, Sunitinib, Nilotinib, Sorafenib

Oncology (N=5)

Medina et al[10] Tocilizumab Immune suppressant (N=1)

Heimke et al[11] Rivastigmine, Paroxetine, Iloperidone, Lamotrigine,

Fluvoxamine

CNS agent (N=5)

Casteele et al[12] Natalizumab, Temsirolimus Immune suppressant (N=2)

Non-linear pharmacokinetic profiles are a great challenge for therapeutic management due to unpredictable behavior of drugs in vivo. This can be due to saturation of the enzyme they interact with, autoinduction, auto-inhibition and a variety of other mechanisms. By reverting to package information to determine nonlinear properties exist, it may be difficult to know where to find this information as there are an extensive amount of graphs that need to be analyzed or key terms that could be missing in the search process. Thus, it’s important for healthcare professionals to stay consistent with any new drugs that may reach the market. We discovered there does not to appear any significance in medication classes between linear and nonlinear drugs found within 2000-2015. That being said, careful monitoring of drugs that are nonlinear with narrow therapeutic windows is extremely crucial not only to provide the most benefits to the patient, but to also provide the best safety outcome. It is in the best interest of the healthcare professional to always examine the package insert for newer drugs that they may be unfamiliar with in therapy. Future considerations should address the need of a searchable database regarding nonlinear drugs that can better optimize the quality and care the patient receives.