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The third trimester of pregnancy is related to physiological changes that can modify the process of absorption, distribution, metabolism, and excretion and, consequently, the efficacy and toxicity of drugs. However, little is known about furosemide pharmacokinetics and placental transfer in pregnancy. This study evaluated the maternal-fetal pharmacokinetics and distribution to amniotic fluid of furosemide in hypertensive parturient women under cesarean section. Twelve hypertensive parturient women under methyldopa (250 mg/8 h) and/or pindolol (10 mg/12 h) treatment received a 40-mg single oral dose of furosemide 1 to 10 hours before delivery by cesarean section. Blood and urine samples were collected for 12 hours after furosemide administration. At delivery, samples were obtained from maternal and umbilical cord blood (n = 8) to assess the transplacental transfer. Amniotic fluid (n = 4) was collected at the time of delivery. The following furosemide pharmacokinetic parameters were obtained as median (interquartile range): C max , 403 ng/mL (229 to 715 ng/mL); T max , 2.00 hours (1.50 to 4.83 hours); elimination half-life (t 1/2 ), 2.50 hours (1.77 to 2.97 hours); AUC 0-12 h , 1366 ng⋅h/mL (927 to 2531 ng⋅h/mL); AUC 0-∞ , 1580 ng⋅h/mL (1270 to 2881 ng⋅h/mL); CL/F 25.3 L/h (13.8 to 31.4 L/h); CLR, 2.50 L/h (1.77 to 2.97 L/h); CLNR, 22.7 L/h (12.1 to 25.6 L/h); and V d /F 82.8 L (34.4 to 173 L). The transplacental transfer of furosemide was 0.43 (0.10 to 0.73), and the amniotic fluid concentration was 11.0 ng/mL (5.51 to 14.6 ng/mL). From a clinical point of view, these results suggest that substrates of uridine diphosphate-glucuronosyltransferase isoenzymes such as furosemide may have increased clearance during pregnancy and could require dose adjustment in this population., (© 2020, The American College of Clinical Pharmacology.)

Angiotensin-converting enzyme (ACE) inhibitors have earned an important place in medical therapy since their discovery about two decades ago. This family of drug has grown tremendously since the introduction of captopril in 1981. There are currently more than 14 ACE inhibitors in the world and 9 are available in the United States. Although these agents share many similarities, they differ in their pharmacokinetic properties, approved indications, and cost. This paper provides guidance for selection of ACE inhibitors by examining the pharmacokinetics, pharmacodynamics, drug interactions, adverse effects, and cost of these agents. Combination products of ACE inhibitors with either diuretics or calcium channel blockers also are reviewed.

Hypertension and diabetes mellitus are a malignant combination of diseases for the kidney. They markedly increase the risk for progressive renal injury and are the largest single cause of renal failure. Strategies to reduce the risk for renal injury in hypertensive diabetics are very important. Although Type I and Type II diabetes are different diseases, they may be associated with similar mechanisms of renal injury in hypertensive patients. Reduction of elevated systemic arterial pressure is of proven benefit in limiting progressive renal injury in diabetic hypertensives. However, converting enzyme inhibitors and possibly the nondihydropyridine calcium antagonists may possess antiproteinuric abilities independent of blood pressure reduction which, in addition to their antihypertensive effects, may be important in limiting the progression of human diabetic renal disease. Long-term clinical trials have evaluated the impact of these and other agents on progression of diabetic renal disease. This paper reviews these trials and focuses on renal effects of antihypertensive agents independent of blood pressure reduction.