1. Academic Validation
  2. A Dose Ranging Pharmacokinetic Evaluation of IQP-0528 Released from Intravaginal Rings in Non-Human Primates

A Dose Ranging Pharmacokinetic Evaluation of IQP-0528 Released from Intravaginal Rings in Non-Human Primates

  • Pharm Res. 2017 Oct;34(10):2163-2171. doi: 10.1007/s11095-017-2224-1.
Jonathan T Su 1 Ryan S Teller 1 Priya Srinivasan 2 Jining Zhang 3 Amy Martin 2 Samuel Sung 1 James M Smith 2 Patrick F Kiser 4 5
Affiliations

Affiliations

  • 1 Department of Biomedical Engineering, Northwestern University, 2145 Sheridan Road, Tech E310, Evanston, Illinois, 60208, USA.
  • 2 Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
  • 3 Total Solutions Inc., Atlanta, Georgia, USA.
  • 4 Department of Biomedical Engineering, Northwestern University, 2145 Sheridan Road, Tech E310, Evanston, Illinois, 60208, USA. Patrick.kiser@northwestern.edu.
  • 5 Department of Obstetrics and Gynecology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA. Patrick.kiser@northwestern.edu.
Abstract

Purpose: Design of intravaginal rings (IVRs) for delivery of antiretrovirals is often guided by in vitro release under sink conditions, based on the assumption that in vivo release will follow a similar release profile.

Methods: We conducted a dose-ranging study in the female reproductive tract of pigtail macaques using matrix IVRs containing IQP-0528, a poorly soluble but highly potent antiretroviral drug with an IC90 of 146 ng/mL. These IVRs consisted of drug-loaded segments, 15.6% IQP-0528 in Tecoflex 85A, comprising either all, half, or a quarter of the entire ring.

Results: In vitro release under sink conditions demonstrates loading-proportional release, with a cumulative 30-day release of 48.5 ± 2.2 mg for our 100% loaded ring, 24.8 ± .36 mg from our 50% loaded ring, and 13.99 ± 1.58 mg from our 25% loaded ring. In vivo, while drug concentration in vaginal fluid is well in excess of IQP-0528's EC90, we find no statistical difference between the different ring loadings in either swab drug levels or drug released from our rings.

Conclusions: We show that in vitro release may not accurately reflect in vivo release, particularly for poorly soluble drugs. All tested loadings of our IVRs are capable of delivering IQP-0528 well in excess of the IC90.

Keywords

IQP-0528; intravaginal rings; macaque; pharmacokinetics.

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