Maternal steady-state

Crofton KM, DeVito M, Kodavanti PR, et al Developmental exposure to Arochlor 1254 using a maternal steady-state exposure model hormonal, hepatic, reproductive and neurotoxic effects. Toxicologist 42(1-S) 164, 1998... 

A 21-year-old woman with a 2-year history of bipolar disorder stopped all of her medication when she discovered that she was pregnant she was given risperidone 2.5 months after childbirth, gradually increasing to a steady-state dosage of 6 mg/day. Risperidone and 9-hydroxyrisperidone concentrations in plasma and breast milk were measured, and calculations indicated that a suckling infant would receive only 0.84% of the maternal dose as risperidone and 3.46% as 9-hydroxy-risperidone. 

Distributed parameter, nonlinear, partial differential equations were soloed to describe oxygen transport from maternal to fetal bloody which flows in microscopic channels within the human placenta. Steady-state solutions were obtained to show the effects of variations in several physiologically important parameters. Results reported previously indicate that maternal contractions during labor are accompanied by a partially reduced or a possible total occlusion of maternal blood flow rate in some or all portions of the placenta. Using the mathematical modely an unsteady-state study analyzed the effect of a time-dependent maternal blood flow rate on placental oxygen transport during labor. Parameter studies included severity of contractions and periodicity of flow. The effects of axial diffusion on placental transport under the conditions of reduced maternal blood flow were investigated. 

Divisions of Analysis. The preceding model describes conditions within a single fetal capillary surrounded by a thin tissue cylinder and supplied by a cylindrical annulus of maternal blood, as shown in Figure 3. Since the numerical techniques required for the solution of such equations were not well defined, the determination of a steady-state concurrent solution was first obtained. Based upon the results of this work, an unsteady-state concurrent solution was assumed possible and feasible. 

Equation (11) represents steady-state conditions within the maternal intervillous channel and is a nonlinear, partial difference equation with two independent variables. Since the dP/dr = 0 when r = R2> a special equation was also required at this position. The same techniques were used as in the fetal capillary equation. 

Sampling. For steady-state experiments, glucose was added continuously to the maternal reservoir. The placenta was weighed before being placed in the artificial uterus, the rate of utilization of glucose by the placenta was then estimated, and the rate of glucose added was set approximately to the estimated rate of utilization. 

Under steady-state conditions the problem of glucose uptake in the tissue disappears, and the rate of metabolism is exactly the rate of utilization. No significant difference in the results was observed or expected when the fetal flow rate was changed since with steady-state conditions in the system there is no net transfer at the fetal surface. The utilization rate depends upon the steady-state maternal and fetal concentrations. This rate is constant for a considerable time. 

On the fetal side, the curves either level off after about 60 min when steady state is reached on the maternal side, or increase continuously if the maternal concentration increases with time. 

The concentration change of the maternal fluid and fetal fluid during a single pass is assumed to be negligible. At steady state, this assump-... 

The steady-state maternal glucose utilization rate can be calculated for a normal maternal glucose concentration of 120 mg % from the rate at which glucose diffuses into the placental tissue at steady state. This is given by ... 

Desipramine is a dihydrodibenzazepine secondary amine TCA that also is the active metabolite of imipramine (Fig. 21.8). Desipramine appears to have a bioavailability comparable to the other secondary TCAs (Table 21.3). Desipramine is distributed into milk in concentrations similar to those present at steady state in maternal plasma. This drug is metabolized primarily by CYP2D6 to its 2-hydroxy metabolite and by CYP1A2 and CYP2C19 to its N-demethylated (primary amine) metabolite (Table 21.2). 

Maprotiline is slowly but completely absorbed from the Gl tract, and like the other TCAs, it is metabolized by the polymorphic CYP2D6 and CYP2C19 isoforms in the liver, primarily to pharmacologically active N-desmethylmaprotiline and to maprotiline-N-oxide. Its pharmacokinetics are shown in Table 21.3. Maprotiline is distributed into breast milk at concentrations similar to those found at steady state in maternal blood. The elimination half-life of maprotiline averages 43 hours (60-90 hours for its N-desmethyl metabolite). 

The steady state levels of choline were reported to be reduced in the midbrain but not in other areas from rats exposed to lead via milk from maternal rats consuming a diet of 4% lead carbonate and weaned to a diet containing 40 ppm Pb (Shih and Hanin, 1977 1978a). 

Ropivacaine is 94% bound to alpha-1 glycoprotein and is mainly protein-bound. After intravascular infusion, steady-state volume of distribution is 41 ht-ers. In addition, ropivacaine readily crosses the placenta and unbound concentration equilibrium is quickly reached. The degree of plasma protein binding in the fetus is less than in the mother. This results in lower total plasma concentrations in the fetus than in the mother. The ratios of umbilical vein to maternal vein total and free concentrations are 0.31 and 0.74, respectively. 

The potential dose equivalent rate to the fetal thyroid from foods produced in air containing 1 pCi m" can be estimated. As determined above, an assumed 30 percent thyroid uptake, a 100-day biologic half-time and a 17-g thyroid in the mother (ICRP, 1975) would result in a steady-state maternal thyroidal burden of 43 pCi, or 2.5 pCi g thyroid for each pCi ingested daily. Such a burden would lead to a dose equivalent rate of 3 mrem y (7 X 10 mrem d" ). If a 3-fold increase in concentration in the fetal thyroid relative to that of the maternal gland is assumed, based upon chronic exposures (Book and Goldman, 1975), then the near-term fetus would contain... 

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