Bioequivalence and Food Effect Assessment of 2 Fixed-Dose Combination Formulations of Dolutegravir and Lamivudine.
Clin Pharmacol Drug Dev
; 9(2): 189-202, 2020 02.
Article
in En
| MEDLINE
| ID: mdl-31724343
ABSTRACT
This single-dose study evaluated the bioequivalence, food effect, and safety of 2 experimental, 2-drug, fixed-dose formulations of 50 mg dolutegravir and 300 mg lamivudine (formulation AH and formulation AK) as compared with coadministration of single-entity tablets of 50 mg dolutegravir and 300 mg lamivudine (reference). In fasted subjects, formulation AH lamivudine exposure was similar to the reference; however, dolutegravir exposure was consistently higher in formulation AH, with area under the concentration-time curve (AUC) and maximum concentration (Cmax ) approximately 27% to 28% greater than reference. Formulation AK met bioequivalence standards to the reference for dolutegravir (AUC0-∞ and Cmax ) and lamivudine (AUC0-∞ and AUC0-t ) exposure; however, dolutegravir AUC0-t and lamivudine Cmax were approximately 16% and 32% higher than the reference, respectively. A high-fat meal increased dolutegravir AUC and Cmax by up to 33% and 21%, respectively, and decreased lamivudine Cmax by approximately 30%. Both test and reference formulations were well tolerated. The results support further development of formulation AK as a novel, 2-drug, fixed-dose combination tablet treatment for patients with HIV.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Oxazines
/
Piperazines
/
Pyridones
/
HIV Infections
/
Fasting
/
Lamivudine
/
Food
/
Heterocyclic Compounds, 3-Ring
Type of study:
Clinical_trials
/
Guideline
/
Prognostic_studies
Limits:
Adult
/
Female
/
Humans
/
Male
/
Middle aged
Language:
En
Journal:
Clin Pharmacol Drug Dev
Year:
2020
Document type:
Article
Affiliation country:
Estados Unidos