Lopinavir and tenofovir interaction observed in non-pregnant adults altered during pregnancy.
J Clin Pharm Ther
; 46(5): 1459-1464, 2021 Oct.
Article
in En
| MEDLINE
| ID: mdl-34254323
ABSTRACT
WHAT IS KNOWN AND OBJECTIVE:
Tenofovir exposure is increased in non-pregnant adults when tenofovir disoproxil fumarate is coadministered with lopinavir/ritonavir. In pregnant women, tenofovir exposure is decreased. Our objective is to describe the effect of lopinavir/ritonavir on tenofovir pharmacokinetics during pregnancy.METHODS:
Data were collected through the International Maternal Pediatric and Adolescent AIDS Clinical Trials (IMPAACT) Network P1026s protocol. This was a nonrandomized, open-label, parallel-group and multicentre phase-IV prospective study in pregnant women with HIV. Intensive steady-state 24-h pharmacokinetic profiles were collected during the third trimester of pregnancy and postpartum. Tenofovir was measured in plasma using validated liquid chromatography-mass spectrometry method (quantification limit 10 ng/ml). Statistical tests compared paired and between group pharmacokinetic data. RESULTS ANDDISCUSSION:
In women not receiving lopinavir/ritonavir (n = 28), tenofovir AUC0-24 was 27% lower (2.2 mcg·h/ml vs 2.8 mcg·h/ml, p = 0.002) and oral clearance was 27% higher (61 L/h vs 48 L/h, p = 0.001) during the third trimester compared to paired postpartum data. In women receiving lopinavir/ritonavir (n = 10), tenofovir AUC0-24 and oral clearance were not different antepartum compared to postpartum. Women with and women without concomitant lopinavir/ritonavir displayed no significant differences in postpartum tenofovir pharmacokinetics. WHAT IS NEW ANDCONCLUSION:
Tenofovir exposure during the third trimester was reduced compared to postpartum in pregnant women not receiving lopinavir/ritonavir, but not in pregnant women also receiving lopinavir/ritonavir. Our findings suggest that pregnancy confounds the expected decrease in tenofovir exposure with concomitant lopinavir/ritonavir in non-pregnant adults. These findings illustrate the need for drug-drug interaction studies in pregnant women as drug disposition differs significantly in pregnant women compared to non-pregnant adults.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Ritonavir
/
Anti-HIV Agents
/
Lopinavir
/
Tenofovir
Type of study:
Guideline
/
Observational_studies
/
Prognostic_studies
Limits:
Adolescent
/
Adult
/
Female
/
Humans
/
Middle aged
/
Pregnancy
Language:
En
Journal:
J Clin Pharm Ther
Journal subject:
FARMACIA
/
TERAPEUTICA
Year:
2021
Document type:
Article
Affiliation country:
Estados Unidos