Clinical Pharmacokinetics of Atropine Administered Ocularly Using an Ultrasensitive Bioanalytical Assay.

Previous pharmacokinetic studies conducted on atropine sulfate ophthalmical solution have utilized bioanalytical assays that lacked sufficient sensitivity to fully characterize the complete pharmacokinetic profile. To address these limitations, Pharma Medica Research Inc. has developed and validated an ultrasensitive bioanalytical method capable of accurately quantifying the active enantiomer, L-hyoscyamine, with a very low limit of quantitation of 0.

A Novel Faster-Acting, Dry Powder-Based, Naloxone Intranasal Formulation for Opioid Overdose.

Objective: To examine the pharmacokinetics and safety of FMXIN001, a new intranasal powder-based naloxone formulation, in comparison to Narcan® nasal liquid spray.

Methods: FMXIN001, was developed by blending drug microspheres with larger lactose monohydrate particles, that serve as diluent and carrier, as well as a disaggregating agent. Scanning electron microscopy and X-ray were used to characterize the formulation and in vitro deposition was investigated using a nasal cast.

A single-dose, comparative bioavailability study comparing amphetamine extended-release oral suspension with extended-release mixed amphetamine salts capsules.

Background: To evaluate the relative bioavailability of a single dose of amphetamine extended-release oral suspension (AMPH EROS) compared with a single dose of extended-release mixed amphetamine salts (ER MAS) in healthy, fasted adult subjects.

Methods: The study population consisted of healthy adult volunteers. The study drug used in this study was 7.

The Pharmacokinetics of Fluticasone Furoate Given Intranasally in Healthy Subjects Using an Ultra-Sensitive Analytical Assay.

Purpose: It has been previously shown that the complete pharmacokinetic profile, in particular the elimination phase, of intranasal fluticasone furoate has not been fully characterized due to the inability to quantify concentrations at low enough levels. This study was designed to evaluate the pharmacokinetic profile of intranasal FF using a validated, ultra-sensitive analytical method in healthy subjects.

Methods: This was an open-label, single-dose, two-period, one-treatment, crossover study.

A Pharmacokinetic Evaluation of Dabigatran Etexilate, Total Dabigatran, and Unconjugated Dabigatran Following the Administration of Dabigatran Etexilate Mesylate Capsules in Healthy Male and Female Subjects.

Purpose: Due to bioanalytical limitations it was previously not possible to evaluate the pharmacokinetics of dabigatran etexilate. We have developed validated methods to assay dabigatran etexilate, unconjugated dabigatran, and total dabigatran that will allow for a complete investigation into the pharmacokinetics of dabigatran etexilate mesylate. This study was designed to evaluate the pharmacokinetics of these analytes in healthy subjects.

An evaluation of the pharmacokinetics of tiotropium following a single-dose inhalation in healthy subjects using an ultra-sensitive bioanalytical method.

The systemic bioavailability of tiotropium following administration via inhalation is known to be very low. A validated ultra-sensitive bioanalytical method with the lowest lower limit of quantitation (LLOQ) was developed and used to evaluate the complete pharmacokinetic profile of tiotropium. This was a pharmacokinetic study performed in 18 healthy subjects.

GCC Consolidated Feedback to ICH on the 2019 ICH M10 Bioanalytical Method Validation Draft Guideline.

The 13 GCC Closed Forum for Bioanalysis was held in New Orleans, Louisiana, USA on April 5, 2019. This GCC meeting was organized to discuss the contents of the 2019 ICH M10 Bioanalytical Method Validation Draft Guideline published in February 2019 and consolidate the feedback of the GCC members. In attendance were 63 senior-level participants from eight countries representing 44 bioanalytical CRO companies/sites.

12th GCC Closed Forum: critical reagents; oligonucleotides; CoA; method transfer; HRMS; flow cytometry; regulatory findings; stability and immunogenicity.

The 12th GCC Closed Forum was held in Philadelphia, PA, USA, on 9 April 2018. Representatives from international bioanalytical Contract Research Organizations were in attendance in order to discuss scientific and regulatory issues specific to bioanalysis. The issues discussed at the meeting included: critical reagents; oligonucleotides; certificates of analysis; method transfer; high resolution mass spectrometry; flow cytometry; recent regulatory findings and case studies involving stability and nonclinical immunogenicity.

Evaluation of the Pharmacokinetic Interaction Between Doravirine and Methadone.

Doravirine is a novel nonnucleoside reverse transcriptase inhibitor indicated for the treatment of HIV type 1 infection. A subset of people living with HIV receives methadone for the treatment of opioid addiction. The current study (NCT02715700) was an open-label, multiple-dose, drug interaction study in participants on a methadone maintenance program to investigate potential drug-drug interactions between doravirine and methadone.

Single-Dose Pharmacokinetics of Amphetamine Extended-Release Oral Suspension in Healthy Adults.

This single-dose pivotal study evaluated the pharmacokinetics of amphetamine extended-release oral suspension (AMPH EROS) under fasted and fed conditions and the relative bioavailability of AMPH EROS and immediate-release mixed amphetamine salts (IR MAS) in adults. This open-label, randomized, three-period, three-treatment, six-sequence crossover study enrolled 30 healthy adult participants who were randomly assigned to receive either 1 dose of AMPH EROS 18.8 mg under fed or fasted conditions or 30 mg of IR MAS under fasted conditions.

Recommendations for classification of commercial LBA kits for biomarkers in drug development from the GCC for bioanalysis.

Over the last decade, the use of biomarker data has become integral to drug development. Biomarkers are not only utilized for internal decision-making by sponsors; they are increasingly utilized to make critical decisions for drug safety and efficacy. As the regulatory agencies are routinely making decisions based on biomarker data, there has been significant scrutiny on the validation of biomarker methods.

Evaluation of the Pharmacokinetics of Abiraterone Acetate and Abiraterone Following Single-Dose Administration of Abiraterone Acetate to Healthy Subjects.

Background And Objective: Following oral administration of abiraterone acetate, the parent compound abiraterone acetate is rapidly metabolized to abiraterone. To our knowledge, bioanalytical methods to date have not been able to detect the parent compound in human plasma, and bioassay was only performed on the metabolite. A highly sensitive bioanalytical method was developed and validated to measure plasma concentrations of the parent compound.

11th GCC Closed Forum: cumulative stability; matrix stability; immunogenicity assays; laboratory manuals; biosimilars; chiral methods; hybrid LBA/LCMS assays; fit-for-purpose validation; China Food and Drug Administration bioanalytical method validation.

The 11th Global CRO Council Closed Forum was held in Universal City, CA, USA on 3 April 2017. Representatives from international CRO members offering bioanalytical services were in attendance in order to discuss scientific and regulatory issues specific to bioanalysis. The second CRO-Pharma Scientific Interchange Meeting was held on 7 April 2017, which included Pharma representatives' sharing perspectives on the topics discussed earlier in the week with the CRO members.

The 10th GCC Closed Forum: rejected data, GCP in bioanalysis, extract stability, BAV, processed batch acceptance, matrix stability, critical reagents, ELN and data integrity and counteracting fraud.

The 10th Global CRO Council (GCC) Closed Forum was held in Orlando, FL, USA on 18 April 2016. In attendance were decision makers from international CRO member companies offering bioanalytical services. The objective of this meeting was for GCC members to meet and discuss scientific and regulatory issues specific to bioanalysis.

9th GCC closed forum: CAPA in regulated bioanalysis; method robustness, biosimilars, preclinical method validation, endogenous biomarkers, whole blood stability, regulatory audit experiences and electronic laboratory notebooks.

The 9th GCCClosed Forum was held just prior to the 2015 Workshop on Recent Issues in Bioanalysis (WRIB) in Miami, FL, USA on 13 April 2015. In attendance were 58 senior-level participants, from eight countries, representing 38 CRO companies offering bioanalytical services. The objective of this meeting was for CRO bioanalytical representatives to meet and discuss scientific and regulatory issues specific to bioanalysis.

8th GCC: consolidated feedback to US FDA on the 2013 draft FDA guidance on bioanalytical method validation.

The 8th GCC Closed Forum for Bioanalysis was held in Baltimore, MD, USA on 5 December 2013, immediately following the 2013 AAPS Workshop (Crystal City V): Quantitative Bioanalytical Methods Validation and Implementation--The 2013 Revised FDA Guidance. This GCC meeting was organized to discuss the contents of the draft revised FDA Guidance on bioanalytical method validation that was published in September 2013 and consolidate the feedback of the GCC members. In attendance were 63 senior-level participants, from seven countries, representing 46 bioanalytical CRO companies/sites.

Recommendations on incurred sample stability (ISS) by GCC.

The topic of incurred sample stability (ISS) has generated considerable discussion within the bioanalytical community in recent years. The subject was an integral part of the seventh annual Workshop on Recent Issues in Bioanalysis (WRIB) held in Long Beach, CA, USA, in April 2013, and at the Global CRO Council for Bioanalysis (GCC) meeting preceding it. Discussion at both events focused on the use of incurred samples for ISS purposes in light of results from a recent GCC survey completed by member companies.

Recommendations on bioanalytical method stability implications of co-administered and co-formulated drugs by Global CRO Council for Bioanalysis (GCC).

An open letter written by the Global CRO Council for Bioanalysis (GCC) describing the GCC survey results on stability data from co-administered and co-formulated drugs was sent to multiple regulatory authorities on 14 December 2011. This letter and further discussions at different GCC meetings led to subsequent recommendations on this topic of widespread interest within the bioanalytical community over the past 2 years.

4th Global CRO Council for Bioanalysis: coadministered drugs stability, EMA/US FDA guidelines, 483s and carryover.

The Global CRO Council for Bioanalysis (GCC) was formed in September 2010. Since then, the representatives of the member companies come together periodically to openly discuss bioanalysis and the regulatory challenges unique to the outsourcing industry. The 4th GCC Closed Forum brought together experts from bioanalytical CROs to share and discuss recent issues in regulated bioanalysis, such as the impact of coadministered drugs on stability, some differences between European Medicines Agency and US FDA bioanalytical guidance documents and lessons learned following recent Untitled Letters.

The pharmacokinetics and cardiovascular effects of high-dose articaine with 1:100,000 and 1:200,000 epinephrine.

Objectives: The authors conducted a randomized, double-blind, two-way crossover clinical trial to compare the pharmacokinetics and cardiovascular effects of 11.9 milliliters of 4 percent articaine hydrochloride (HCl) plus 1:100,000 epinephrine (A100) with those of 11.9 mL of 4 percent articaine HCl plus 1:200,000 epinephrine (A200).