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Lopinavir and tenofovir interaction observed in non‐pregnant adults altered during pregnancy
Author(s) -
Mulligan Nikki,
Salama Engie,
Momper Jeremiah D.,
Capparelli Edmund V.,
Stek Alice,
Chakhtoura Nahida,
Mirochnick Mark,
Best Brookie M.
Publication year - 2021
Publication title -
journal of clinical pharmacy and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.622
H-Index - 73
eISSN - 1365-2710
pISSN - 0269-4727
DOI - 10.1111/jcpt.13477
Subject(s) - lopinavir , ritonavir , lopinavir/ritonavir , medicine , pregnancy , pharmacokinetics , obstetrics , gestation , pharmacology , human immunodeficiency virus (hiv) , viral load , virology , antiretroviral therapy , biology , genetics
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 and discussion In women not receiving lopinavir/ritonavir ( n = 28), tenofovir AUC 0‐24 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 AUC 0‐24 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 and conclusion 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.