Metoclopramide Pharmacokinetics in Pregnant and Nonpregnant Sheep

Riggs, K. Wayne; Axelson, James E.; Gruber, Nancy; McErlane, B; McMorland, G. H.; Rurak, Dan

doi:10.1002/jps.2600770502

Cited by 13 publications

(5 citation statements)

References 34 publications

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“…FX is highly lipophilic (log octanol/water partition coefficient ϭ 4.05). However, its F/M AUC ratio is lower than the values for diphenhydramine (0.85) and metoclopramide (0.82), both of which have substantially lower partition coefficient values of 3.1 and 1.1, respectively (Yoo et al, 1986;Riggs et al, 1988). The reduced fetal exposure to fluoxetine, compared with these two drugs, is likely due to the high plasma protein binding of the drug, which can also reduce maternal-fetal drug transfer .…”

Section: Discussionmentioning

confidence: 92%

Stereoselective Pharmacokinetics of Fluoxetine and Norfluoxetine Enantiomers in Pregnant Sheep

Kim¹,

Riggs²,

Rurak³

2004

Drug Metabolism and Disposition

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This article is available online at http://dmd.aspetjournals.org ABSTRACT:We examined the stereoselective disposition of fluoxetine (FX) and its metabolite norfluoxetine (NFX) in five pregnant sheep. Racemic FX was administered i.v. to the ewe (50 mg) and the fetus (10 mg) on separate occasions. Maternal and fetal blood, maternal urine, and fetal amniotic and tracheal fluid samples were collected for 72 h. FX and NFX isomers were quantified by gas chromatographymass spectrometry. They rapidly crossed the placenta [maternal to fetal area under the plasma concentration versus time curve (AUC) ratios 0.59 and 0.65, respectively]. There was significant FX stereoselectivity with S/R FX AUC ratios averaging 1.65 ؎ 0.33 and 1.73 ؎ 0.29 in ewe and fetus, respectively, after maternal dosing. The maternal clearance and volume of distribution were also higher for (R)-fluoxetine than for (S)-fluoxetine. FX, NFX, and their glucuronides were present in maternal urine but accounted for only 3.4% of maternal drug elimination. In contrast, NFX was not detected in the fetus after fetal FX administration, which is consistent with the absence of measurable fetal nonplacental clearance of the drug and the lack of NFX formation in fetal hepatic microsomal incubations. There was also no fetal production of FX and NFX glucuronides in vivo. Both FX and NFX were extensively and stereoselectively bound in maternal and fetal plasma, with the free fraction S/R FX ratio averaging 0.46 ؎ 0.06 and 0.58 ؎ 0.10 in ewe and fetus, respectively. Thus, FX exhibits extensive stereoselective disposition, which is likely due to differential plasma protein binding of the FX isomers, and there is no detectable fetal formation of NFX, FX, and NFX glucuronides.

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Section: Discussionmentioning

confidence: 92%

Stereoselective Pharmacokinetics of Fluoxetine and Norfluoxetine Enantiomers in Pregnant Sheep

Kim¹,

Riggs²,

Rurak³

2004

Drug Metabolism and Disposition

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“…Similarly, Al-Qadri et al (2020) recorded that the Cl_F_obs was significantly decreased in pregnant ewes. This is likely due to reduced hepatic blood flow and hepatic metabolism during pregnancy (Riggs et al 1988).…”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetics of toltrazuril and its metabolites toltrazuril sulphoxide and toltrazuril sulphone in pregnant and non-pregnant goats

2021

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The pharmacokinetic characteristics of toltrazuril (TZR) and its metabolites toltrazuril sulphoxide (TZR.SO) and toltrazuril sulphone (TZR.SO2) were assessed in non-pregnant and pregnant goats. Ten healthy Baladi female goats were allocated into two groups (n = 5 per group): non-pregnant goats (group 1) and pregnant goats at 2–3 months of gestation (group 2). Toltrazuril was administered once orally to all goats at 20 mg/kg. Plasma samples were collected at 0 (before TZR administration), 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72 h and 5, 7, 9, 12, 16, 20, 24, 27, 30, and 35 days post therapy to measure the concentrations of TZR and its metabolites. In pregnant goats, the maximum plasma concentration (Cmax), time to reach Cmax (Tmax), and the area under the plasma concentration-time curve from time zero to the last sample (AUC0-last) of TZR were significantly higher (P < 0.05) compared to the non-pregnant ones, whereas the volume of distribution (Vz_F_obs) and clearance (Cl_F_obs) were significantly lower (P < 0.05) in pregnant goats. No significant differences were observed in the elimination half-life (T1/2λz), and mean residence time (MRT) between the two groups. In non-pregnant goats, TZR.SO and TZR.SO2 could be detected in plasma until 12 and 30 days, respectively; whereas in pregnant goats, they were quantified up to 16 and 35 days, respectively. Conclusively, TZR was well absorbed and rapidly metabolized to TZR.SO and TZR.SO2, after oral dosing in goats. Pregnancy caused significant alterations in some of the pharmacokinetic indicators of TZR and its metabolites in goats.

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“…Sterile silicone rubber catheters (Dow Corning, Midland, MI), filled with heparinized 0.9% saline (12 unitdml), were implanted into the fetal femoral artery, lateral tarsal vein, trachea, and amniotic cavity and in a maternal femoral artery and vein as previously described. 9 All vascular catheters were kept patent by flushing daily with sterile 0.9% saline containing 12 units of heparidml. In five fetuses, electrodes of polytetrafluoroethylene-coated stainless steel wire (Cooper Corp., Chatsworth, CA) were implanted biparietally on the dura to record the fetal electroencephalograph and through the orbital ridge of the zygomatic bone of each eye for electroocular recordings.…”

Section: Methodsmentioning

confidence: 99%

“…Ampicillin was administered to the ewe and fetus following surgery and prophylactically into the amniotic fluid as in our previous study. 9 Following surgery, the ewes were kept in holding pens with other sheep and given free acceM to food and water. All animals were allowed to recover for a minimum of 3 days (mean 5 ?…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Fetal and Maternal Placental and Nonplacental Clearances of Metoclopramide in Chronically Instrumented Pregnant Sheep

Riggs

Rurak

Taylor

et al. 1990

Journal of Pharmaceutical Sciences

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Metoclopramide Pharmacokinetics in Pregnant and Nonpregnant Sheep

Cited by 13 publications

References 34 publications

Stereoselective Pharmacokinetics of Fluoxetine and Norfluoxetine Enantiomers in Pregnant Sheep

Stereoselective Pharmacokinetics of Fluoxetine and Norfluoxetine Enantiomers in Pregnant Sheep

Pharmacokinetics of toltrazuril and its metabolites toltrazuril sulphoxide and toltrazuril sulphone in pregnant and non-pregnant goats

Fetal and Maternal Placental and Nonplacental Clearances of Metoclopramide in Chronically Instrumented Pregnant Sheep

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