Drug disposition and pharmacokinetics in the maternal-placental-fetal unit

Krauer, Béatrice; Krauer, F.; Hytten, F. E.

doi:10.1016/0163-7258(80)90085-6

Cited by 134 publications

(64 citation statements)

References 126 publications

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“…The exact mechanism for the increase in the volume of distribution of dexamethasone in pregnant diabetic rats is not clear from our studies; it could have been caused by various pregnancy associated physiological changes (Krauer et al, 1980) and diabetic pregnancy associated metabolic disturbance (Pedersen, 1977).…”

Section: Discussionmentioning

confidence: 58%

Influence of streptozotocin‐diabetes on the pharmacokinetics, placental transfer and tissue localization of dexamethasone in rats

Mulay

Varma

1984

British J Pharmacology

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The influence of streptozotocin‐diabetes on the pharmacokinetics, placental transfer and tissue localization of dexamethasone was determined in Sprague‐Dawley rats. Diabetes significantly increased the volume of distribution of dexamethasone in pregnant but not in nonpregnant rats; plasma half‐life was not significantly increased. Concentrations of maternally administered dexamethasone in all tissues studied (maternal and foetal serum and livers, foetal lungs and placentas) except the amniotic fluid were lower in diabetic than in control animals. Diabetes did not alter the binding of dexamethasone to maternal or foetal serum proteins. Insulin treatment partially reversed the effects of diabetes on the maternal‐foetal exchange of dexamethasone. Diabetes‐induced decrease in the foetal localization of dexamethasone appears to be caused by a decrease in the maternal serum levels as well as by an increase in the foetal excretion of the steroid into the amniotic fluid. In so far as the rat model reflects the human situation, the present data suggest that a standard dose of dexamethasone might not be adequate in promoting foetal lung maturation in diabetic pregnancies.

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Section: Discussionmentioning

confidence: 58%

Influence of streptozotocin‐diabetes on the pharmacokinetics, placental transfer and tissue localization of dexamethasone in rats

Mulay

Varma

1984

British J Pharmacology

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“…Interindividual pharmacokinetic and pharmacodynamic variability is usually substantial and may be augmented by pregnancy (1). During pregnancy multiple changes in physiology occur affecting the major pharmacokinetic processes including absorption, distribution, metabolism and excretion (2).…”

Section: Introductionmentioning

confidence: 99%

Pharmacokinetics of chemotherapeutic agents in pregnancy: a preclinical and clinical study

Calsteren¹,

Verbesselt

Ottevanger

et al. 2010

Acta Obstet Gynecol Scand

104

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Objective. To determine the impact of physiologic changes of pregnancy on pharmacokinetics of chemotherapeutic agents. Design. A preclinical and a clinical case-control trial. Setting. Institute of Primate Research Nairobi and collaborating hospitals in Belgium, the Netherlands and Czech Republic. Population. Pregnant and nonpregnant women and baboons receiving chemotherapy. Methods. Chemotherapy pharmacokinetics was compared between the pregnant and nonpregnant state. Standard-dosed chemotherapy regimens were administered in pregnant and nonpregnant baboons/women, followed by serial blood samplings. Drug plasma levels were determined using high performance liquid chromatography and atomic absorption spectrometry. Main outcome measures. Area under the curve (AUC), maximal plasma concentration, terminal elimination half-life, clearance and distribution volume of each drug in pregnant and nonpregnant state. Results. Intraindividual comparative pharmacokinetic data were obtained for doxorubicin and paclitaxel/platinum in three and two baboons, respectively. In the clinical trial, two patients were exposed to doxorubicin and one patient was exposed to paclitaxel/ platinum during and after pregnancy. Furthermore, a pooled analysis was performed based on 16 cycles of pregnant and 11 cycles of nonpregnant women. Numbers of pregnant/nonpregnant patients were 5/2, 7/5, 4/4 and 2/2 for paclitaxel, doxorubicin, epirubicin and platinum, respectively. For all drugs tested in the preclinical and clinical study, a decreased AUC and maximal plasma concentration and an increased distribution volume and clearance were observed in pregnancy. Conclusions. Although numbers were too small for statistical significance, pregnancy-associated physiologic alterations appear to lead to a decrease in plasma exposure of chemotherapeutic drugs. The importance of long-term follow-up of women treated with chemotherapy during pregnancy is underscored.

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“…The figures 73 suggest that absorption was reduced by 10-20% in these patients who, it should be noted, were not in labour while on oral treatment (cessation of labour being the prerequisite for the commencement of oral therapy). Although a reduction of drug absorption in pregnancy is expected (Krauer et al, 1980), our data suggest that absorption of salbutamol in pregnancy is nevertheless relatively efficient. This would not necessarily be the case for patients in labour (Krauer et al, 1980).…”

Section: Nsmentioning

confidence: 65%

“…However, renal clearance of salbutamol was significantly lower in premature labour, in parallel with a lower creatinine clearance. The lower renal clearance of salbutamol was unexpected as previous studies have shown an increase in renal drug clearance in pregnancy (O'Hare etal., 1983;Luxford & Kellaway, 1983;Chow & Jewesson, 1985), due to increased renal blood flow and glomerular filtration rate (Krauer et al, 1980). The below normal creatinine clearance in our patients could be an effect of the drug, as suggested to occur with fenoterol in premature labour (Paulin & Csomor, 1982) or associated with premature labour itself.…”

Section: Nsmentioning

confidence: 89%

Pharmacokinetics and metabolism of salbutamol in premature labour.

Hutchings

Paull

Wilson‐Evered

et al. 1987

Brit J Clinical Pharma

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1 The pharmacokinetics of salbutamol and its sulphate conjugate were examined during intravenous and steady‐state oral administration in nine patients receiving the drug for the prevention or treatment of premature labour. 2 Uterine contractions were inhibited by plasma salbutamol concentrations in the range 8‐33 ng ml‐1 in six of the seven patients who were receiving intravenous drug. 3 By comparison with our previous study in a control group of healthy males and nonpregnant females, the total clearance of salbutamol in premature labour (501; s.d. 185 ml min‐1) was similar to that in the control group (480; s.d. 123 ml min‐1). Renal salbutamol clearance (208; s.d. 51 ml min‐1), however, was significantly less than that in the control group (283; s.d. 51 ml min‐1). 4 The systemic availability (n = 3), urinary recovery of unchanged oral salbutamol and area under the plasma curve during the oral dosage interval (n = 5) were all only slightly lower (10‐20%) than control values, suggesting slightly lower oral absorption. 5 Formation and elimination of the sulphate conjugate were similar to those observed in control subjects suggesting that first‐ pass sulphation in the gut wall is unchanged in pregnancy. Overall there were only minor differences in salbutamol pharmacokinetics between control subjects and patients in premature labour.

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Drug disposition and pharmacokinetics in the maternal-placental-fetal unit

Cited by 134 publications

References 126 publications

Influence of streptozotocin‐diabetes on the pharmacokinetics, placental transfer and tissue localization of dexamethasone in rats

Influence of streptozotocin‐diabetes on the pharmacokinetics, placental transfer and tissue localization of dexamethasone in rats

Pharmacokinetics of chemotherapeutic agents in pregnancy: a preclinical and clinical study

Pharmacokinetics and metabolism of salbutamol in premature labour.

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