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u.washington.edu
OBJECTIVE: To assess the risks and potential benefits of low-dose angiotensin-converting enzyme (ACE) inhibitor treatment in pregnancies complicated by severe hypertension. METHODS: A retrospective review of pregnant women treated with ACE inhibitors was conducted. Hemodynamics before and after treatment were assessed by using Doppler technique to measure cardiac output. Data were analyzed by using the Wilcoxon signed-rank test. Maternal and neonatal outcomes were assessed by chart review and phone interview. RESULTS: Ten pregnancies were identified in which ACE inhibitor therapy was initiated in pregnancy for severe, unresponsive vasoconstricted hypertension; three were complicated by severe chronic hypertension, 4 by renal insufficiency, and 3 by severe preeclampsia. Treatment was limited to a low-dose, short-acting ACE inhibitor (captopril, 12.5 to 25 mg/day). Treatment was associated with an increase in cardiac output from 5.7 +/- 1.5 L/minute to 7.4 +/- 1.4 L/minute (P<.01) and a reduction in total peripheral resistance from 1770 +/- 670 to 1222 +/- 271 dyne. sec. cm(-5) (P =.005). No fetal or neonatal complications were observed. The probability of observing one or more adverse neonatal outcome in this sample, based on an assumed true risk of 5% and 10%, was calculated to be 12% and 50%, respectively. CONCLUSION: Low-dose captopril therapy was associated with improvement in maternal hemodynamics and, in cases complicated by severe hypertension and renal insufficiency, successful continuation of pregnancy. Fetal and neonatal complications were not experienced, but complication rates of 5-10% could have been missed because of the small number of exposed pregnancies.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11084185&dopt=Abstract
Int J Pharm. 2000 Nov 19;209(1-2):87-94.
Evaluation of pharmacokinetics and pharmacodynamics of captopril from transdermal hydrophilic gels in normotensive rabbits and spontaneously hypertensive rats.
Wu PC, Huang YB, Chang JJ, Chang JS, Tsai YS.
School of Pharmacy, Kaohsiung Medical University, 100 Shih-Chen 1st R.D., 807, Kaohsiung, Taiwan, ROC. pachwu
kmu.edu.tw
The purpose of this investigation was to assess the pharmacokinetics (plasma concentration) and pharmacodynamics (heart rate, blood pressure (BP), and plasma renin activity (PRA)) of captopril experimental gel in normotensive rabbits and spontaneously hypertensive rats (SHRs) by reference to a short duration intravenous administration of the drug. In normotensive rabbits, the blood concentration versus time course of captopril after transdermal administration could be described well by a two-compartment model, and the maximum plasma concentration (5. 68+/-2.05 microg ml(-1)) was achieved in about 7 h. The increase in plasma captopril concentration led to increases in PRA and reductions in BP. A simple E(max) model adequately described the relationship between the percentage change of mean blood pressure (MBP) and the blood concentration of the captopril. The maximum reduction in MBP (E(max)) was 36.23% and the concentration at half maximum effect (EC(50)) was 0.24 microg ml(-1). The captopril was continuously released from the gel formulation and protected the SHRs in lower BP throughout the period of transdermal therapy. These results indicated that the development of captopril transdermal drug delivery system was possible. Further research was warranted on a modified formulation of captopril, which was optimized for transdermal delivery of the drug.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11084249&dopt=Abstract
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