Amoxicillin is recommended for anthrax prevention in pregnancy. The objective of this study was to evaluate the pharmacokinetics of amoxicillin during pregnancy and postpartum (PP). Sixteen women received amoxicillin during gestation (18-22 weeks (T2) and 30-34 weeks (T3)) as well as 3 months postpartum (PP) to evaluate single-dose pharmacokinetics. Amoxicillin compartmental pharmacokinetic parameters were used to simulate amoxicillin concentration-time profiles following different dosage strategies. Amoxicillin CL(renal) (T2: 24.8+/-6.7 l/h, P<0.001; T3: 24.0+/-3.9 l/h, P<0.001; and PP: 15.3+/-2.6 l/h) and renal CL(secretion) (T2: 280+/-105 ml/min, P<0.002; T3: 259+/-54 ml/min, P<0.001; and PP: 167+/-47 ml/min) were higher during pregnancy than postpartum. Simulations suggest that amoxicillin concentrations adequate to prevent anthrax may be difficult to achieve during pregnancy and postpartum. Increases in amoxicillin CL(renal) and renal CL(secretion) reflect increases in filtration and secretory transport or diminished reabsorption in the kidneys. Amoxicillin may not be an appropriate antibiotic for post-anthrax exposure prophylaxis.

ABSTRACT:The objective of this study was to determine the pharmacokinetic parameters of clonidine during pregnancy compared with previously published data in nonpregnant subjects. Serial blood and urine samples were collected in 17 women during mid to late pregnancy over one steady-state dosing interval to determine clonidine noncompartmental pharmacokinetic parameters (n ‫؍‬ 17) and creatinine clearance. In six of these pregnant subjects, maternal and umbilical cord (venous and arterial) plasma samples were collected at the time of delivery for measurement of clonidine concentrations. Clonidine apparent oral clearance was found to be 440 ؎ 168 ml/min during pregnancy compared with 245 ؎ 72 ml/min as previously reported in nonpregnant subjects (p < 0.0001) (Cunningham et al., 1994). There was a strong correlation (r ‫؍‬ 0.82, p < 0.001) between clonidine renal clearance, adjusted for variation in glomerular filtration rate, and urine pH. Umbilical cord to maternal plasma clonidine concentration ratios were 1.0 ؎ 0.1 (arterial) and 1.0 ؎ 0.1 (venous). In conclusion, clonidine is cleared more rapidly in pregnant women than in nonpregnant subjects. At the time of delivery, the fetus is exposed to similar plasma clonidine concentrations as the mother.Chronic hypertension during pregnancy is associated with complications, including fetal growth restriction, premature birth, preeclampsia, placental abruption, hypertensive crisis, and in some cases fetal demise. Very little information is available on the pharmacokinetic changes that occur for antihypertensive medications during pregnancy. Clonidine, a centrally acting, ␣-2 adrenergic agonist, has been used for the treatment of hypertension during pregnancy (Kobinger, 1978;Hartikainen-Sorri et al., 1987). In the nonpregnant population, approximately 60% of clonidine is eliminated unchanged by the kidneys (Davies et al., 1977). There are significant changes in kidney function during pregnancy, with creatinine clearance reported to increase by 50 to 60% (Davison and Noble, 1981). The pharmacokinetics of clonidine have not been studied during pregnancy. The objective of this study was to characterize the pharmacokinetics of clonidine during pregnancy. Materials and MethodsAfter receiving written informed consent from patients, we examined steady-state pharmacokinetics of orally administered clonidine in the plasma of 17 pregnant women receiving clonidine during mid pregnancy (22-26 weeks gestation) or late pregnancy (34 -38 weeks gestation). Six of these women participated in maternal and umbilical cord (arterial and venous) plasma sample collections at the time of delivery for measurement of clonidine concentrations. Gestational age was based on the last menstrual period or early ultrasound dating.Subject Selection. This study was approved by the University of Washington Investigational Review Board. Subjects were eligible to participate if they were pregnant, 18 years of age, had a hematocrit Ն28%, and were receiving oral clonidine for maternal hypertension. Dosing Regi...

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Our objectives were to evaluate the time course for atenolol pharmacokinetics in lactating women postpartum and to quantify atenolol plasma concentrations in their 3-4 months old nursing infants. Data were collected over one dosing interval from lactating women treated with atenolol for therapeutic reasons, at 2-4 weeks (n=32), 3-4 months (n=22), and 6-8 months (n=17) postpartum. A single blood sample was collected from 15 nursing infants (3-4 months of age) of the mothers participating in the study. At 2-4 weeks, 3-4 months, and 6-8 months postpartum, atenolol infant dose, relative to the mother's weight-adjusted dose, were 14.6 ± 7.6%, 8.3 ± 5.2% and 5.9 ± 2.9%, respectively. Over this time, maternal atenolol pharmacokinetics did not change to a clinically significant extent. Atenolol concentrations were below assay quantification limits (< 10 ng/mL) in the plasma of all 3-4 months old nursing infants studied. Our findings support the careful use of atenolol during breastfeeding, since in the vast majority of healthy, term infants, atenolol concentrations will be too low to be clinically relevant. Premature infants and those with kidney disease require further study. Infant exposure depends on maternal dose and decreases during the first 6-8 months postpartum.