Dataset Information

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

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.

SUBMITTER: Su JT

PROVIDER: S-EPMC7036280 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

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Publications

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

Su Jonathan T JT Teller Ryan S RS Srinivasan Priya P Zhang Jining J Martin Amy A Sung Samuel S Smith James M JM Kiser Patrick F PF

Pharmaceutical research 20170802 10

<h4>Purpose</h4>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.<h4>Methods</h4>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 IC<sub>90</sub> of 146 ng/mL. These IVRs consisted of drug-loaded seg ...[more]

PMID: 28770490

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Project description:BackgroundZoonotic diseases are a serious threat to both public health and animal conservation. Most non-human primates (NHP) are facing the threat of forest loss and fragmentation and are increasingly living in closer spatial proximity to humans. Humans are infected with soil-transmitted helminths (STH) at a high prevalence, and bidirectional infection with NHP has been observed. The aim of this study was to determine the prevalence, genetic diversity, distribution and presence of co-infections of STH in free-ranging gorillas, chimpanzees and other NHP species, and to determine the potential role of these NHP as reservoir hosts contributing to the environmental sustenance of zoonotic nematode infections in forested areas of Cameroon and Gabon.MethodsA total of 315 faecal samples from six species of NHPs were analysed. We performed PCR amplification, sequencing and maximum likelihood analysis of DNA fragments of the internal transcribed spacer 2 (ITS2) nuclear ribosomal DNA to detect the presence and determine the genetic diversity of Oesophagostomum spp., Necator spp. and Trichuris spp., and of targeted DNA fragments of the internal transcribed spacer 1 (ITS1) to detect the presence of Ascaris spp.ResultsNecator spp. infections were most common in gorillas (35 of 65 individuals), but also present in chimpanzees (100 of 222 individuals) and in one of four samples from greater spot-nosed monkeys. These clustered with previously described type II and III Necator spp. Gorillas were also the most infected NHP with Oesophagostomum (51/65 individuals), followed by chimpanzees (157/222 individuals), mandrills (8/12 samples) and mangabeys (7/12 samples), with O. stephanostomum being the most prevalent species. Oesophagostomum bifurcum was detected in chimpanzees and a red-capped mangabey, and a non-classified Oesophagostomum species was detected in a mandrill and a red-capped mangabey. In addition, Ternidens deminutus was detected in samples from one chimpanzee and three greater spot-nosed monkeys. A significant relative overabundance of co-infections with Necator and Oesophagostomum was observed in chimpanzees and gorillas. Trichuris sp. was detected at low prevalence in a gorilla, a chimpanzee and a greater spot-nosed monkey. No Ascaris was observed in any of the samples analysed.ConclusionsOur results on STH prevalence and genetic diversity in NHP from Cameroon and Gabon corroborate those obtained from other wild NHP populations in other African countries. Future research should focus on better identifying, at a molecular level, the species of Necator and Oesophagostomum infecting NHP and determining how human populations may be affected by increased proximity resulting from encroachment into sylvatic STH reservoir habitats.

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Dataset Information

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

Purpose

Methods

Results

Conclusions

Publications

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

Similar Datasets

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