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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.

Our main objective was to investigate the numbers of days necessary for the disappearance of the cough caused by an angiotensin‐converting enzyme inhibitor (ACEI) subsequent to the discontinuation of treatment, and to identify the associated factors that contribute to the appearance of said cough and angioneurotic edema. We studied 1101 patients with hypertension treated with an ACEI for 15 years. A multivariate analysis of binary logistic regression was performed to identify predisposing cough factors. In the 1101 patients treated with ACEI, 270 were diagnosed as having a cough caused by an ACEI (24.5%). The average numbers of days until the cough disappeared was 6.06 ± 1.58 days. The significant predisposing factors of the cough were female sex (odds ratio [OR], 1.77; 95% confidence interval [CI], 1.31‐2.39), previous diagnosis of obstructive sleep apnea (OR, 1.85; 95% CI, 1.31‐2.61), and concomitant use of thiazides (OR, 1.50; 95% CI, 1.11‐2.04). Statins were shown as a protective factor (OR, 0.69; 95% CI, 0.51‐0.93). In the case of angioneurotic edema, 25 patients (2.3%) were diagnosed, without significant determinants. Our analysis showed that the cough disappeared in a period of ≤10 days for 96.7% of patients diagnosed with a cough, subsequent to the discontinuation of ACEI treatment. The risk factors identified for the appearance of a cough include female sex, previous obstructive sleep apnea, and concomitant use of thiazides. The use of statins was found to be a protective factor. The incidence of angioneurotic edema in our cohort is greater than that described in the literature. [ABSTRACT FROM AUTHOR]

This randomized, double-blind, placebo-controlled study assessed the efficacy, safety, and tolerability of aliskiren 75, 150, and 300 mg to clarify the dose-response relationship and characterize the optimum aliskiren dose when given with a light meal to elderly hypertensive patients. After washout, 754 patients aged ≥65 years with hypertension (mean sitting systolic blood pressure [msSBP] ≥150 and <180 mm Hg; mean sitting diastolic blood pressure [msDBP] <110 mm Hg) were randomized to aliskiren 75, 150, or 300 mg or placebo for 8 weeks; medication was taken each morning with a light meal. The primary efficacy variable was change in msSBP from baseline to week 8 end point. Change from baseline in msDBP and dose-response curves for aliskiren 75, 150, and 300 mg were also assessed. At week 8 end point, all 3 aliskiren doses provided significantly greater least squares mean reductions in msSBP/msDBP (75 mg, 13/5 mm Hg; 150 mg, 15/6 mm Hg; 300 mg, 14/7 mm Hg) compared with placebo (8/4 mm Hg; P < .05). Aliskiren was generally well tolerated at all doses. There was a significant dose-response relationship for aliskiren, with an estimated minimum effective dose of 81.9 mg. In conclusion, aliskiren 150 and 300 mg provided effective blood pressure control in elderly patients when given with a light meal. [ABSTRACT FROM PUBLISHER]

Single-pill combinations (SPCs) of complementary antihypertensive agents provide patients with a simple and effective treatment regimen. To ensure that the efficacy and safety of an SPC is the same as that for the individual drugs administered together (free combination), SPC and free-combination formulations must be shown to be bioequivalent. Three open-label, randomized studies compared the pharmacokinetics of SPC tablets of the direct renin inhibitor aliskiren and hydrochlorothiazide (HCT), at doses of 150/25, 300/12.5, and 300/25 mg, with the corresponding free combinations in healthy volunteers. Data from 2 randomized, double-blinded studies of patients with hypertension were used to assess inhibition of plasma renin activity (PRA) by the aliskiren/HCT 300/25 mg SPC and the free combination. At all dose combinations, aliskiren and HCT systemic drug exposure was similar when administered as an SPC or free combination, indicating bioequivalence. Aliskiren/HCT 300/25 mg SPC inhibited PRA to the same extent as the free combination. HCT alone increased PRA through activation of the renin-angiotensin system; aliskiren prevented this diuretic-induced increase to the same extent when administered as the free combination or as the SPC. In conclusion, aliskiren/HCT SPCs are pharmacokinetically and pharmacodynamically bioequivalent to aliskiren and HCT in free combination. [ABSTRACT FROM PUBLISHER]

Drug interactions are a significant clinical concern, particularly in patients with conditions such as heart disease and hypertension, in whom coadministration of multiple drugs is common. Nebivolol is a selective β1-blocker with vasodilatory properties approved for the treatment of hypertension. Drug—drug interactions were investigated when nebivolol was coadministered to subjects classified as poor CYP2D6 metabolizers and extensive CYP2D6 metabolizers who were receiving other drugs commonly administered to patients with hypertension or compounds metabolized by cytochrome P450 (CYP) 2D6. There were no drug—drug interactions when nebivolol was coadministered with hydrochlorothiazide, furosemide, ramipril, losartan, digoxin, or warfarin. Coadministration with fluoxetine (also metabolized by CYP2D6) in extensive CYP2D6 metabolizers impeded the apparent clearance of nebivolol. The authors conclude that nebivolol is safe and well tolerated regardless of genotype and type of medication coadministered. [ABSTRACT FROM PUBLISHER]

A letter to the editor is presented in response an article on a research conducted on the role of soluble VEGFR-1 biomarker in causing hypertension in patients with advanced tumors treated with sorafenib, that was published in a previous issue.