Ex Vivo Human Placental Transfer of Anti-Human Immunodeficiency Virus Compounds

Objective: The transfer of anti-human immunodeficiency virus (HIV) drugs has been studied in the ex vivo human placental model. There is a paucity of information on the placental transfer of these drugs because of ethical considerations and the expense involved in the use of the non-human primate model

The Bidirectional Transfer and Fetal Vascular Pressure Changes Due to the Presence of [Formula: see text] I-Labeled Inhibin A in the ex-vivo Human Placental Model

Objective: The purpose of this study was to investigate the transport of inhibin A and to determine its effects on fetal vascular pressure at elevated levels in the human placenta using (125)I -labeled synthetic glycoprotein. Methods: Synthetic inhibinAwas prepared and was shown to be consistent with the natural form by high-pressure liquid chromatography (HPLC) and molecular weight determination by gas-chromatography mass spectrometry. The standardized Na(125)I process yielded (125)I -labeled inhibin A with a radioactivity of 10(6) cpm/μg. This compound was placed in the human placenta in maternal–fetal and fetal–maternal studies using antipyrine and (14)C -labeled inulin as controls to determine the bidirectional transfer of the compound. Results: Maternal–fetal and fetal–maternal clearance indices were 0.045± 0.003 and 0, respectively. In eight placentas there was no evidence of vascular pressure changes due to the presence of up to 5000 pg of inhibin A. Conclusions: There is minimal maternal–fetal transfer and no detectable fetal–maternal transfer in normotensive and pregnancy-induced hypertensive placentas. In addition, there are no pressure changes in the fetal vascular system due to the clinically significant levels of inhibin A

Transfer of meropenem in the ex vivo human placenta perfusion model.

OBJECTIVES: To determine maternal-fetal transplacental passage of meropenem in the ex vivo human perfusion model. STUDY DESIGN: Term placentae (n = 6) were collected immediately after delivery. A single cotyledon was localized, perfused and stabilized with physiologic Eagles minimal essential medium containing 3% bovine albumin and heparin as described by Chalier (Chalier JC. Criteria for evaluating perfusion experiments and presentation results. Contrib Gynecol Obstet 1985; 13:32 - 39). Meropenem was added to the maternal medium in concentrations similar to maternal serum peak and trough levels, then perfused through the maternal circulation of the cotyledon. To assess transfer and accumulation, fluid aliquots from both the maternal and fetal compartments were collected over an hour at defined intervals in an open and closed system. Antipyrine 14C was added to the medium in order to calculate the transport fraction and clearance indexes. Meropenem and antipyrine 14C concentrations were determined by High-pressure Liquid Chromatography and liquid scintillation, respectively. RESULTS: Mean antipyrine transport fraction was 2.33 + 0.25. Maternal and fetal mean meropenem peak concentrations were 54.3 + 3.3 microg/ml and 2.2 + 0.18 microg/ml, respectively. Whereas, maternal and fetal mean trough concentrations were 12.7 + 1.3 microg/ml and 0.41 + 0.10 microg/ml, respectively. Mean peak clearance index was 0.077 + 0.007 and the mean trough was 0.052 + 0.015. Mean accumulation for the peak and trough concentrations of meropenem were 0.9 and 2.95 microg/ml, respectively. CONCLUSIONS: Transplacental passage of meropenem was incomplete in the ex vivo human placental perfusion model. Accumulation was also noted in the fetal compartment

The Metabolism and Transplacental Transfer of Oseltamivir in the Ex Vivo Human Model

Oseltamivir phosphate is extensively metabolized in the ex vivo human placenta model, and the transplacental passage of the metabolite oseltamivir carboxylate is incomplete. Objective. To evaluate the metabolism and transplacental transfer of oseltamivir (Tamiflu) in the ex vivo human placental model. Study Design. Perfusion studies were performed in six placentas from term, uncomplicated deliveries. Concentrations of oseltamivir phosphate (OP) that were 5-6 fold, 20–30 fold, and 600–800 fold above the therapeutic peak were tested, as neither OP nor its active metabolite, oseltamivir carboxylate (OC), could be detected at near-therapeutic concentrations. The transplacental transfer and accumulation of OC were assessed using the 14C antipyrine reference method. Results. OP was extensively metabolized to OC. In the 4 placentas with the highest concentration of OP, OC had a mean clearance index of 0.13 ± 0.08, suggesting that transplacental passage occurs at a relatively low rate. Measurable fetal accumulation occurred in the two placentas with the highest initial concentrations. Conclusions. Oseltamivir phosphate was extensively metabolized in the ex vivo model. Transplacental transfer of the metabolite was incomplete and accumulation was minimal

Transplacental passage of vancomycin in the ex vivo human perfusion model.

OBJECTIVES: To determine maternal-fetal transplacental passage of vancomycin in the ex vivo human placental perfusion model. METHODS: Six term placentas were collected immediately after delivery and perfused with physiologic medium using the single cotyledon perfusion system. Vancomycin was added to the maternal medium and perfused through the maternal circulation of the cotyledon. Over a 1-h period in an open system, samples of the perfusate were collected at defined intervals from the fetal venous catheter and from the maternal effluence to assess vancomycin transfer. Thereafter, the system was closed for 1-5 h to establish accumulation. Transport fraction and clearance indexes were calculated by perfusing antipyrine 14C (positive control). Vancomycin was estimated by high pressure liquid chromatography and antipyrine 14C concentration was determined by liquid scintillation. RESULTS: Mean vancomycin maternal peak and trough concentrations ranged from 30.0 to 51.5 microg/ml and 7.7 to 16.4 microg/ml, respectively. Clearance indexes were minimal with a mean peak range of 0.000-0.080 and a mean trough range of 0.00-0.17. For each placenta, transport fraction for antipyrine 14C was > 1.85 with a single pass of > 40%. No accumulation of vancomycin was noted when the system was closed for 1-5 h. The mean peak clearance index was zero after perfusing the placenta for up to 5 h with 35.8 microg/ml of vancomycin. CONCLUSION: Transplacental passage of vancomycin was minimal in the ex vivo human placental perfusion model, with no detectable accumulation

Teratogenic and Embryocidal Effects of Zidovudine (AZT) in Sprague-Dawley Rats

Objective: The purpose of the present investigation was to analyze the effets of zidovudine on the postimplantation embryo and fetus

CLINICAL STUDY Transfer of meropenem in the ex vivo human placenta perfusion model

Abstract Objectives. To determine maternal-fetal transplacental passage of meropenem in the ex vivo human perfusion model. Study design. Term placentae (n = 6) were collected immediately after delivery. A single cotyledon was localized, perfused and stabilized with physiologic Eagles minimal essential medium containing 3% bovine albumin and heparin as described by Chalier (Chalier JC. Criteria for evaluating perfusion experiments and presentation results. Contrib Gynecol Obstet 1985; 13:32-39). Meropenem was added to the maternal medium in concentrations similar to maternal serum peak and trough levels, then perfused through the maternal circulation of the cotyledon. To assess transfer and accumulation, fluid aliquots from both the maternal and fetal compartments were collected over an hour at defined intervals in an open and closed system. Antipyrine 14 C was added to the medium in order to calculate the transport fraction and clearance indexes. Meropenem and antipyrine 14 C concentrations were determined by High-pressure Liquid Chromatography and liquid scintillation, respectively. Results. Mean antipyrine transport fraction was 2.33 + 0.25. Maternal and fetal mean meropenem peak concentrations were 54.3 + 3.3 mg/ml and 2.2 + 0.18 mg/ml, respectively. Whereas, maternal and fetal mean trough concentrations were 12.7 + 1.3 mg/ml and 0.41 + 0.10 mg/ml, respectively. Mean peak clearance index was 0.077 + 0.007 and the mean trough was 0.052 + 0.015. Mean accumulation for the peak and trough concentrations of meropenem were 0.9 and 2.95 mg/ml, respectively. Conclusions. Transplacental passage of meropenem was incomplete in the ex vivo human placental perfusion model. Accumulation was also noted in the fetal compartmen