Lionel Trottet

Assessing Drug Concentration in Skin: Direct and Indirect Methods

This chapter reviews the most commonly used topical pharmacokinetic techniques. Numerous other techniques (e.g., the non-invasive spectroscopic techniques like confocal, fluorescence techniques as well as the NMR technique) are not described here as they will have one or more of the following characteristics: very specific for a drug or disease, possibly impractical, possibly not quantitative, possibly lacking sensitivity or possibly at a too early stage of development. They cannot, therefore, be applicable as versatile techniques for studying topical pharmacokinetics.

Key Factors Affecting the Efficacy of a Topical Drug Candidate: Learnings from Past Topical Drug Development

This chapter focuses on lessons learned from the success and failure of topical drug development over the last 60 years. First, the skin barrier quality for a particular skin disease will be compared to the easiness of topical drug development. The importance of the candidate molecule potency will be considered as well in comparison to its clinical efficacy.

Topical Versus Oral/Systemic Drug Discovery

Over the past decades, the drug discovery process of the pharmaceutical industry has vastly improved.

Assessing Therapeutic Index

One key advantage of a topical administration is the decreased risk of toxicological findings. This perceived element is generally the driving rationale for developing a topical medicine.

Selecting Dermal Drug Candidate: Some Useful Quotations and “Rules”

In the preceding chapters, several elements and concepts have emerged. In order to put in perspectives some of them in the industrial context, some quotations and rules are listed in this chapter. Extra comments met during the course of various topical drug development programs are added too. Overall these quotations and rules, sometimes considered provocative, may be found helpful for program teams developing a topical molecule.

Choosing Topical Drug Candidate: Historical Overview

Historically most topical drug classes seem to have been originally developed following the pragmatic principle that, “if an existing drug with an interesting pharmacology is effective orally/systemically, and the target is in the skin, it could well work topically without giving side effects and, therefore, would deserve to be tried topically”.

Topical Vehicle Selection: Myths and Reality

During the development of a dermal drug, much efforts tend to be placed on improving its delivery through skin. These efforts are driven by the known risk of not engaging the target. Indeed to increase comfort that the target will be engaged one need to try fullfill as best as it can evidence of (1) sufficient compound on board for a desired time (i.e., PK within skin) and (2) demonstration of pharmacological activity [1].

Assessing Topical Efficacy

As seen previously, a large part of the selection of a candidate process for an oral/systemic application relies on the use of plasma exposure and in vitro potency. This allows translating reachable plasma exposure (pharmacokinetics) into reachable in vivo pharmacodynamic effect: This is PharmacoKinetic/Pharmacodynamic (PK/PD) (Fig. 6.1).

Dermal Drug Development Strategies

As seen in Chap. 1, the pharma industry nowadays works on more therapeutic targets than it used to do thanks to the advances in the understanding of the molecular basis of diseases as well as the push from payors to deliver better medicines compared to standard of care. This presents a strong opportunity for pharma companies who want to invest into dermal drug development projects as more assets and more therapeutic targets are becoming available.

Topical Drug Candidate Selection Criteria and Cascade

A key objective of the drug discovery project team is to discharge as much risk as possible for the selected candidate such that the best possible molecule can be progressed.