MK-0736

11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) may be involved in several abnormalities associated with the metabolic syndrome. This study evaluated the antihypertensive efficacy and safety of two 11β-HSD1 inhibitors, MK-0736 and MK-0916, in overweight-to-obese hypertensive patients. Patients aged 18-75 years with sitting diastolic blood pressure (SiDBP) 90-104 mm Hg, systolic BP <160 mm Hg (after washout of prior antihypertensive medications), and BMI ≥27 to <41 kg/m(2) were randomized to receive 2 or 7 mg/d MK-0736, 6 mg/d MK-0916, or placebo for 12 weeks (n = 51-54/group). Patients with BMI ≥20 to <27 kg/m(2) received 6 mg/d MK-0916 or placebo for 24 weeks (n = 19/group). The primary endpoint was placebo-adjusted change from baseline in trough SiDBP in patients treated for 12 weeks with 7 mg/d MK-0736. The primary endpoint was not met (placebo-adjusted reduction = 2.2 mm Hg; P = .157). With 7 mg/d MK-0736, placebo-adjusted LDL-C decreased by 12.3%, high-density lipoprotein cholesterol by 6.3%, and body weight by 1.4 kg. Both 11β-HSD1 inhibitors were generally well tolerated. In overweight-to-obese patients with hypertension, reduction in SiDBP with MK-0736 was not statistically significant. Nonetheless, MK-0736 was well tolerated and did appear to modestly improve other BP endpoints, LDL-C, and body weight.

The 111th Annual Meeting of the American Society for Clinical Pharmacology and Therapeutics, held in Atlanta, included topics covering disclosures of new data in the field of pharmacokinetics and drug interactions. This conference report highlights selected presentations on pharmacokinetic studies of several investigational drugs, including evatanepag (Pfizer Inc), AEG-33773 (Aegera Therapeutics Inc), JNJ-16269110 (Johnson & Johnson Pharmaceutical Research & Development LLC), PF-3716539 (ViiV Healthcare), MK-0736 (Merck & Co Inc), a combination of Ginkgo biloba and cilostazol (Renexin SK Chemicals Co Ltd), PP-101 (Pacific Pharmaceuticals Co Ltd), ACT-178882 (Acetlion Ltd/Merck & Co Inc) and edoxaban (Daiichi Sankyo Co Ltd).