The Effects of Uterine and Umbilical Blood Flows on the Transfer of Propofol Across the Human Placenta During In Vitro Perfusion

He, Yanling; Seno, Hiroshi; Tsujimoto, Saburo; Tashiro, Chikara

doi:10.1097/00000539-200107000-00030

Cited by 16 publications

(6 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Conversely, increased umbilical blood flow facilitated the placental transfer of propofol in vitro. 26 The drugs in this study are known to alter blood flow: medetomidine will decrease blood flow to a range of organs 18 while ketamine has little effect on uterine blood flow. 27,28 The interaction of these effects in this study is unknown.…”

Section: Discussionmentioning

confidence: 98%

“…Uterine and umbilical blood flow will also influence the transfer of drugs across the placental barrier. 26 Increased uterine blood flow is likely to decrease the extraction of drugs by the placenta, and maintain maternal plasma concentrations at a higher level for a longer period of time. Conversely, increased umbilical blood flow facilitated the placental transfer of propofol in vitro.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Transplacental transfer of medetomidine and ketamine in pregnant ewes

et al. 2012

View full text Add to dashboard Cite

The extent of placental transfer of medetomidine and ketamine is unknown in pregnant ewes. Date-mated singleton (n ¼ 8) and twin (n ¼ 8) pregnant merino cross ewes were anaesthetized for Caesarean delivery of preterm lamb fetuses. A combination of medetomidine (20 mg/kg) and ketamine (10 mg/kg) was administered by intravenous injection and surgery performed immediately thereafter. Blood samples were collected from the ewe at one, five and 10 min after intravenous injection and from the umbilical vein of the fetus at delivery. Non-pregnant ewes were also anaesthetized (n ¼ 8). There was no difference in the plasma concentration of medetomidine or ketamine when comparing singleton and twin ewes or pregnant and non-pregnant ewes for the short duration of the study. Fetal plasma concentrations of each drug were comparable to the maternal concentrations at the same time. We conclude that both drugs cross the placenta readily and provide anaesthesia and analgesia for the fetus when it is delivered.

show abstract

Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

Transplacental transfer of medetomidine and ketamine in pregnant ewes

et al. 2012

View full text Add to dashboard Cite

show abstract

“…Flow rates of 3 and 12 ml/min are maintained in the fetal and maternal circulations, respectively. Flow rates used in the perfusion model vary between laboratories 14 and can influence the time to achieve transplacental transfer and steady state between the fetal and maternal circulations 16 , 17 …”

Section: Description Of the Experimental Modelmentioning

confidence: 99%

The Human Placental Perfusion Model: A Systematic Review and Development of a Model to Predict In Vivo Transfer of Therapeutic Drugs

Hutson

Garcia‐Bournissen

Davis

et al. 2011

Clin Pharmacol Ther

169

118

View full text Add to dashboard Cite

Dual perfusion of a single placental lobule is the only experimental model to study human placental transfer of substances in organized placental tissue. To date, there has not been any attempt at a systematic evaluation of this model. The aim of this study was to systematically evaluate the perfusion model in predicting placental drug transfer and to develop a pharmacokinetic model to account for nonplacental pharmacokinetic parameters in the perfusion results. In general, the fetal-to-maternal drug concentration ratios matched well between placental perfusion experiments and in vivo samples taken at the time of delivery of the infant. After modeling for differences in maternal and fetal/neonatal protein binding and blood pH, the perfusion results were able to accurately predict in vivo transfer at steady state (R² = 0.85, P < 0.0001). Placental perfusion experiments can be used to predict placental drug transfer when adjusting for extra parameters and can be useful for assessing drug therapy risks and benefits in pregnancy.

show abstract

“…Propofol pharmacokinetic (PK) properties are well established in pediatric and adult populations, but little is known of propofol disposition in the unborn fetus especially during open fetal surgery. Many in vitro studies using human dually perfused cotyledon demonstrated that propofol is highly lipophilic and rapidly diffuses across the placenta [ 4 , 5 ]; however, the extent of fetal drug exposure during maternal propofol administration is largely unknown. In the third trimester, the fetal exposure of propofol in utero has been studied in parturients undergoing cesarean section.…”

Section: Introductionmentioning

confidence: 99%

Propofol Pharmacokinetics and Estimation of Fetal Propofol Exposure during Mid-Gestational Fetal Surgery: A Maternal-Fetal Sheep Model

et al. 2016

View full text Add to dashboard Cite

BackgroundMeasuring fetal drug concentrations is extremely difficult in humans. We conducted a study in pregnant sheep to simultaneously describe maternal and fetal concentrations of propofol, a common intravenous anesthetic agent used in humans. Compared to inhalational anesthesia, propofol supplemented anesthesia lowered the dose of desflurane required to provide adequate uterine relaxation during open fetal surgery. This resulted in better intraoperative fetal cardiac outcome. This study describes maternal and fetal propofol pharmacokinetics (PK) using a chronically instrumented maternal-fetal sheep model.MethodsFetal and maternal blood samples were simultaneously collected from eight mid-gestational pregnant ewes during general anesthesia with propofol, remifentanil and desflurane. Nonlinear mixed-effects modeling was performed by using NONMEM software. Total body weight, gestational age and hemodynamic parameters were tested in the covariate analysis. The final model was validated by bootstrapping and visual predictive check.ResultsA total of 160 propofol samples were collected. A 2-compartment maternal PK model with a third fetal compartment appropriately described the data. Mean population parameter estimates for maternal propofol clearance and central volume of distribution were 4.17 L/min and 37.7 L, respectively, in a typical ewe with a median heart rate of 135 beats/min. Increase in maternal heart rate significantly correlated with increase in propofol clearance. The estimated population maternal-fetal inter-compartment clearance was 0.0138 L/min and the volume of distribution of propofol in the fetus was 0.144 L. Fetal propofol clearance was found to be almost negligible compared to maternal clearance and could not be robustly estimated.ConclusionsFor the first time, a maternal-fetal PK model of propofol in pregnant ewes was successfully developed. This study narrows the gap in our knowledge in maternal-fetal PK model in human. Our study confirms that maternal heart rate has an important influence on the pharmacokinetics of propofol during pregnancy. Much lower propofol concentration in the fetus compared to maternal concentrations explain limited placental transfer in in-vivo paired model, and less direct fetal cardiac depression we observed earlier with propofol supplemented inhalational anesthesia compared to higher dose inhalational anesthesia in humans and sheep.

show abstract

The Effects of Uterine and Umbilical Blood Flows on the Transfer of Propofol Across the Human Placenta During In Vitro Perfusion

Abstract: Uterine and umbilical blood flows are determinant features in controlling the placental transfer of propofol, and, therefore, changes in these variables would significantly affect the extent of fetal exposure to propofol.

Cited by 16 publications

References 29 publications

Transplacental transfer of medetomidine and ketamine in pregnant ewes

Transplacental transfer of medetomidine and ketamine in pregnant ewes

The Human Placental Perfusion Model: A Systematic Review and Development of a Model to Predict In Vivo Transfer of Therapeutic Drugs

Propofol Pharmacokinetics and Estimation of Fetal Propofol Exposure during Mid-Gestational Fetal Surgery: A Maternal-Fetal Sheep Model

Contact Info

Product

Resources

About