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A Phase 1 Study to Evaluate the Pharmacokinetics and Safety of Cabotegravir in Patients With Hepatic Impairment and Healthy Matched Controls
- Source :
- Clinical Pharmacology in Drug Development
- Publication Year :
- 2019
- Publisher :
- Wiley, 2019.
-
Abstract
- Cabotegravir is an investigational integrase inhibitor in development for the treatment and pre‐exposure prophylaxis of HIV‐1 infection. Liver disease is a major cause of morbidity and mortality in HIV‐infected individuals and can impact the pharmacokinetics (PK) of HIV medications. This phase 1 study evaluated the PK of cabotegravir in individuals with moderate hepatic impairment (n = 8) versus healthy controls (n = 8). Participants received a single oral cabotegravir 30‐mg tablet and underwent PK sampling to determine total and unbound plasma cabotegravir concentrations. Calculated geometric least‐squares mean ratios (90% confidence intervals) for individuals with hepatic impairment versus healthy controls were 0.73 (0.50‐1.06) for AUC0‐∞, 0.69 (0.51‐0.93) for Cmax, 1.40 (0.80‐2.46) for unbound concentration (CU) 2 hours postdose, 1.55 (0.82‐2.94) for CU at 24 hours, 2.14 (1.57‐2.90) for unbound fraction (FU) at 2 hours, and 1.90 (1.14‐3.18) for FU at 24 hours. Adverse events (AEs) occurred in 2 individuals with hepatic impairment and 3 healthy controls and were grade 1/2 in severity. No participant discontinued because of AEs. Increased FU resulted in a modest decrease in total plasma exposure not considered clinically relevant. We conclude that cabotegravir may be administered without dose adjustment in patients with mild to moderate hepatic impairment.
- Subjects :
- Male
medicine.medical_specialty
hepatic impairment
Anti-HIV Agents
Pyridones
Cmax
Administration, Oral
Pharmaceutical Science
Integrase inhibitor
Original Manuscript
protein binding
030226 pharmacology & pharmacy
Gastroenterology
03 medical and health sciences
Liver disease
chemistry.chemical_compound
0302 clinical medicine
Cabotegravir
Pharmacokinetics
Internal medicine
medicine
Hepatic Insufficiency
Humans
Pharmacology (medical)
Adverse effect
business.industry
cabotegravir
Hepatic impairment
Articles
Middle Aged
medicine.disease
Confidence interval
chemistry
030220 oncology & carcinogenesis
Female
business
pharmacokinetics
Subjects
Details
- ISSN :
- 21607648 and 2160763X
- Volume :
- 8
- Database :
- OpenAIRE
- Journal :
- Clinical Pharmacology in Drug Development
- Accession number :
- edsair.doi.dedup.....3d96d97fa9d243ce4da38703cb911027