Pharmacokinetic profiling of efavirenz–emtricitabine–tenofovir fixed dose combination in pregnant and non-pregnant rats Ramakrishna Nirogi a, * , Gopinadh Bhyrapuneni a,b , Vishwottam Kandikere a , Nageswararao Muddana a , Ramanatha Saralaya a , Prashanth Komarneni a , Koteshwara Mudigonda a , and K. Mukkanti b a Pharmacokinetics and Drug Metabolism, Discovery Research, Suven Life Sciences Ltd, Banjara Hills, Hyderabad 500034, India b Institute of Science and Technology, JNT University, Kukatpally, Hyderabad 500072, India ABSTRACT: During pregnancy, the disposition of various drugs is altered due to changes in physiological condition, maternal gastrointestinal absorption, gastric secretion and motility. A fixed dose combination of antiretrovirals is commonly prescribed for the treatment of HIV infection. There is a need to understand the pharmacokinetics and placental transfer of efavirenz–emtricitabine–tenofovir in fixed dose combination during pregnancy. The pharmacokinetics and placental transfer of efavirenz– emtricitabine–tenofovir fixed dose combination was evaluated in timed pregnant and non-pregnant Sprague–Dawley rats at 30, 10, 15 mg/kg p.o., respectively. The plasma, placental tissue, amniotic fluid and fetal tissue concentrations were measured using high performance liquid chromatography combined with tandem mass spectrometric detector (LC-MS/MS). To summarize, the pharmacokinetic profile of efavirenz remained similar in the pregnant and non-pregnant rats. However, a considerable difference in the pharmacokinetics of emtricitabine and tenofovir was observed in pregnant and non-pregnant rats. Efavirenz and emtricitabine showed appreciable placental, amniotic fluid and fetal exposure compared with tenofovir. The present study suggests that a profound impact on antiretroviral pharmacokinetics was observed during pregnancy and there is a need to monitor the exposure levels of each drug when administered as a fixed dose combination during pregnancy. Further studies to explore the pharmacoki- netic parameters of fixed dose antiretrovirals during the preclinical stage in a timed-pregnancy rat model are required. Such studies can help in the development of safe and effective medications with a reduced risk of perinatal transmission of HIV-1 infection. Copyright © 2012 John Wiley & Sons, Ltd. Key words: antiretroviral fixed dose combination; timed pregnant rat pharmacokinetics; placental tissue; amniotic fluid; fetal tissue Introduction Mother-to-child transmission (MTCT) is the most common source of HIV infection in children. As of 2005, more than 38.6 million cases were reported with seropositive human immune deficiency virus (HIV), including approximately 25 million women of child-bearing age and 3 million children, most of whom acquired HIV infection from MTCT [1]. The United Nations conducted a session on reducing the proportion of infants infected with HIV. This session included interventions focusing on the prevention of HIV infection among women and their partners; women to their children; and support for women living with HIV/AIDS and their fami- lies [2]. The risk of mother-to-child transmission of HIV-1 infection can be reduced by prophylactic anti- retroviral therapy during pregnancy, delivery in the neonatal period, elective caesarean section delivery or refraining from breastfeeding [3]. A combination *Correspondence to: Suven Life Sciences Ltd, Serene Chambers, Road No-5, Avenue-7, Banjara Hills, Hyderabad 500 034, India. E-mail: ramakrishna_nirogi@yahoo.co.in, nvsrk@suven.com BIOPHARMACEUTICS & DRUG DISPOSITION Biopharm. Drug Dispos. (2012) Published online in Wiley Online Library (wileyonlinelibrary.com) DOI: 10.1002/bdd.1794 Received 10 October 2011 Revised 10 May 2012 Accepted 14 May 2012 Copyright © 2012 John Wiley & Sons, Ltd.