Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hydrochlorothiazide 775mg was administered orally to 5 patients who had undergone intestinal shunt operations for obesity 1.5 to 6 years previously. Postoperative weight loss averaged 53.4kg. The concentrations of hydrochlorothiazide in plasma and urine were determined with gas/liquid chromatography. The mean area under the plasma concentration time curve during 9h in 4 of the patients was 889ng/ml.h. Mean total urinary recovery of hydrochlorothiazide amounted to 23.0mg in the 5 patients, which corresponds to approximately half that seen in healthy volunteers. The gastrointestinal hydrochlorothiazide appears to be substantially reduced after intestinal shunt surgery.
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PMID:Malabsorption of hydrochlorothiazide following intestinal shunt surgery. 42 12

Because obesity-associated hypertension has unique hemodynamic and hormonal profiles, certain classes of antihypertensive agents may be more effective than others as monotherapy. Thus, we compared the efficacy and safety of the angiotensin-converting enzyme inhibitor lisinopril and the diuretic hydrochlorothiazide in a 12-week, multicenter, double-blind trial in 232 obese patients with hypertension. Patients with an office diastolic pressure between 90 and 109 mm Hg were randomized to treatment with daily doses of lisinopril (10, 20, or 40 mg), hydrochlorothiazide (12.5, 25, or 50 mg), or placebo. Mean body mass indexes were similar for all patients. At week 12, lisinopril and hydrochlorothiazide effectively lowered office diastolic (-8.3 and -7.7 versus -3.3 mm Hg, respectively; P<.005) and systolic (-9.2 and -10.0 versus -4.6 mm Hg, respectively; P<.05) pressures compared with placebo. Ambulatory blood pressure monitoring confirmed that lisinopril and hydrochlorothiazide effectively lowered 24-hour blood pressure compared with placebo (P<.001). Significant dose-response differences were observed between treatments. Sixty percent of patients treated with lisinopril had an office diastolic pressure <90 mm Hg compared with 43% of patients treated with hydrochlorothiazide (P<.05). Responses to therapies differed with both race and age. Neither treatment significantly affected insulin or lipid profiles; however, plasma glucose increased significantly after 12 weeks of hydrochlorothiazide therapy compared with lisinopril (+0.31 versus -0.21 mmol/L; P<.001). Hydrochlorothiazide also decreased serum potassium levels by 0.4 mmol/L from baseline. In conclusion, lisinopril was as effective as hydrochlorothiazide in treating obese patients with hypertension. Treatment with angiotensin-converting enzyme inhibitors may show greater efficacy as monotherapy at lower doses compared with thiazide diuretics, may have a more rapid rate of response, and may offer advantages in patients at high risk of metabolic disorders.
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PMID:Lisinopril versus hydrochlorothiazide in obese hypertensive patients: a multicenter placebo-controlled trial. Treatment in Obese Patients With Hypertension (TROPHY) Study Group. 923 34

Hydrochlorothiazide (HCTZ) is a thiazide diuretic used in adults and children for the treatment of hypertension and edema. The pharmacokinetic (PK) properties of HCTZ in children are not well characterized, particularly among children with obesity who frequently suffer from hypertension and may, therefore, benefit from HCTZ therapy. HCTZ is excreted in the kidney via organic anion transporters 1 and 3 (OAT1 and OAT3). The ontogeny of OAT1 and OAT3 remain unknown, but HCTZ clearance may serve as a surrogate marker of OAT1 and OAT3 maturation. Population PK modeling was performed in NONMEM, and the model was leveraged to conduct dose-exposure simulations. This study examined 83 plasma samples from 49 participants (69% male) taking enteral HCTZ. The median (range) postnatal age was 6.7 years (0.03-19.5 years), and 17 (34%) participants were obese or morbidly obese. The median (range) dose of HCTZ was 0.654 mg/kg (0.11-1.8 kg) and the median number of doses recorded per participant was 5 (1-8). HCTZ PK was well characterized by a 1-compartment PK model. Body weight and a maturation model based on postmenstrual age were significant covariates for apparent clearance, but the presence of obesity was not. Dosing simulations were performed with a standardized 1mg/kg. Simulated exposure (area under the curve and maximum HCTZ concentrations) decreased with age and was likely due to older children receiving the maximum absolute doses of HCTZ. Further studies with more patients in each age group are required to confirm these PK findings of HCTZ in the children.
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PMID:Pharmacokinetics of Hydrochlorothiazide in Children: A Potential Surrogate for Renal Secretion Maturation. 3302 6