Nikki Mulligan1, Engie Salama2, Jeremiah D Momper2, Edmund V Capparelli2,3, Alice Stek4, Nahida Chakhtoura5, Mark Mirochnick6, Brookie M Best2,3. 1. Riverside University Health System, Moreno Valley, CA, USA. 2. Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, CA, USA. 3. Pediatrics Department, School of Medicine, University of California San Diego-Rady Children's Hospital San Diego, San Diego, CA, USA. 4. University of Southern California School of Medicine, Los Angeles, CA, USA. 5. Maternal and Pediatric Infectious Disease Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), Bethesda, MD, USA. 6. Boston University School of Medicine, Boston, MA, USA.
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 AND DISCUSSION: 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 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.
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 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 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.
Authors: Sonia Rodríguez-Nóvoa; Pablo Labarga; Antonio D'avolio; Pablo Barreiro; Marta Albalate; Eugenia Vispo; Carmen Solera; Marco Siccardi; Stefano Bonora; Giovanni Di Perri; Vincent Soriano Journal: AIDS Date: 2010-04-24 Impact factor: 4.177
Authors: B M Best; S Burchett; H Li; A Stek; C Hu; J Wang; E Hawkins; M Byroads; D H Watts; E Smith; C V Fletcher; E V Capparelli; M Mirochnick Journal: HIV Med Date: 2015-05-11 Impact factor: 3.180
Authors: J J Kiser; M L Carten; C L Aquilante; P L Anderson; P Wolfe; T M King; T Delahunty; L R Bushman; C V Fletcher Journal: Clin Pharmacol Ther Date: 2007-06-27 Impact factor: 6.875