title: Challenges regarding analysis of unbound fraction of highly bound protein antiretroviral drugs in several biological matrices: lack of harmonisation and guidelines.
abstract: The unbound drug concentration in plasma is usually considered the only active fraction; thus the binding of a drug to a protein limits its pharmacological actions. This is of special importance for those highly bound drugs. Therefore, binding studies can be of great utility for those drugs where relationship between free and total drug concentration is variable among patients, or it can be altered by some condition or disease, or even by interactions with other drugs. However, there is a lack of validation guidelines for the determination of unbound concentrations. Antiretroviral drugs (ARVs), protease inhibitors (PIs), efavirenz and nevirapine are highly bound to proteins. Here, we present a review on the overall methods for the study of unbound fractions of highly bound plasma protein ARVs. We also provide a critical evaluation of the methods applied, their differences and the main points to be controlled and validated.
authors.affiliation: Unité de Recherche Clinique, AP-HP, Hôpital Tarnier, Paris, France. Electronic address: 07silvia@gmail.com.
authors.forename: Sílvia M
authors.initials: SM
authors.lastname: Illamola
authors.affiliation: Service de Pharmacologie Clinique, AP-HP, Groupe Hospitalier Paris Centre, Paris, France; EA 3620 Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
authors.forename: Déborah
authors.initials: D
authors.lastname: Hirt
authors.affiliation: Unité de Recherche Clinique, AP-HP, Hôpital Tarnier, Paris, France; Service de Pharmacologie Clinique, AP-HP, Groupe Hospitalier Paris Centre, Paris, France; EA 3620 Université Paris Descartes, Sorbonne Paris Cité, Paris, France; CIC-0901 INSERM, Cochin-Necker, Paris, France.
authors.forename: Jean M
authors.initials: JM
authors.lastname: Tréluyer
authors.affiliation: EA 08 Université Paris Descartes, Sorbonne Paris Cité, France Unité de Recherche Clinique, AP-HP, Hôpital Tarnier, Paris, France.
authors.forename: Saik
authors.initials: S
authors.lastname: Urien
authors.affiliation: Service de Pharmacologie Clinique, AP-HP, Groupe Hospitalier Paris Centre, Paris, France; EA 3620 Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
authors.forename: Sihem
authors.initials: S
authors.lastname: Benaboud
mesh_terms: D000480:Alkynes; D000818:Animals; D044966:Anti-Retroviral Agents / Q000097:blood* / Q000134:cerebrospinal fluid / Q000493:pharmacokinetics; D048588:Benzoxazines / Q000097:blood* / Q000134:cerebrospinal fluid / Q000493:pharmacokinetics; D003521:Cyclopropanes; D016903:Drug Monitoring / Q000379:methods / Q000592:standards*; D006801:Humans; D019829:Nevirapine / Q000097:blood* / Q000134:cerebrospinal fluid / Q000493:pharmacokinetics; D017410:Practice Guidelines as Topic / Q000592:standards*; D011237:Predictive Value of Tests; D011485:Protein Binding; D015203:Reproducibility of Results
chemical_list: D000480:Alkynes; D044966:Anti-Retroviral Agents; D048588:Benzoxazines; D003521:Cyclopropanes; D019829:Nevirapine; C098320:efavirenz